Ignite Creation Date:
2025-12-26 @ 10:45 PM
Ignite Modification Date:
2026-01-24 @ 3:12 AM
Study NCT ID:
NCT00377312
Status:
COMPLETED
Last Update Posted:
2016-03-22
First Post:
2006-09-14
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
7 Day Continuous Parathyroid Hormone IV Infusion
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010024', 'term': 'Osteoporosis'}, {'id': 'D001849', 'term': 'Bone Diseases, Endocrine'}, {'id': 'D006961', 'term': 'Hyperparathyroidism'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}], 'ancestors': [{'id': 'D001851', 'term': 'Bone Diseases, Metabolic'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D010279', 'term': 'Parathyroid Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D010281', 'term': 'Parathyroid Hormone'}], 'ancestors': [{'id': 'D036361', 'term': 'Peptide Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'horwitz@pitt.edu', 'phone': '412-692-2848', 'title': 'Mara J Horwitz', 'organization': 'University of Pittsburgh'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Small number of subjects in each group Study limited to Caucasians Only one timepoint for follow-up was measure Study did not include saline infused controls'}}, 'adverseEventsModule': {'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete', 'eventGroups': [{'id': 'EG000', 'title': 'Group 1', 'description': 'PTH (1-34) 2 picomoles (pmols)/kg/hr', 'otherNumAtRisk': 6, 'otherNumAffected': 1, 'seriousNumAtRisk': 6, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Group 2', 'description': 'PTH (1-34) 4 picomoles (pmols)/kg/hr', 'otherNumAtRisk': 5, 'otherNumAffected': 2, 'seriousNumAtRisk': 5, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'hypercalcemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 5, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Endocrine disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'tachycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 5, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Endocrine disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'IV infiltration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 5, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Endocrine disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Participants With Dose Limiting Toxicity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days', 'description': 'DLT was defined as achieving one major criterion or two minor criteria rated at ≥ 2 on a scale of 0-5. The major criteria were defined as symptomatic orthostatic hypotension (systolic BP fall \\>30 mm/hg), tachycardia (pulse \\> 120), hypertension (systolic BP \\>160 mm/hg on 2 occasions), hypercalcemia (serum calcium ≥ 12 mg/dl), and hypophosphatemia (serum phosphorous \\< 1.5 mg/dl). Minor criteria included symptoms such as flushing, nausea, abdominal or muscle cramps, dizziness, lightheadedness, palpitations, etc.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Total Serum Calcium', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '9.33', 'spread': '0.20', 'groupId': 'OG000'}, {'value': '9.11', 'spread': '0.16', 'groupId': 'OG001'}]}]}, {'title': '11P Day 1', 'categories': [{'measurements': [{'value': '9.56', 'spread': '0.19', 'groupId': 'OG000'}, {'value': '9.78', 'spread': '0.21', 'groupId': 'OG001'}]}]}, {'title': '7 A Day 2', 'categories': [{'measurements': [{'value': '9.74', 'spread': '0.15', 'groupId': 'OG000'}, {'value': '10.06', 'spread': '0.22', 'groupId': 'OG001'}]}]}, {'title': '3P Day 2', 'categories': [{'measurements': [{'value': '10.14', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '10.30', 'spread': '0.26', 'groupId': 'OG001'}]}]}, {'title': '11P Day 2', 'categories': [{'measurements': [{'value': '9.84', 'spread': '0.15', 'groupId': 'OG000'}, {'value': '10.38', 'spread': '0.37', 'groupId': 'OG001'}]}]}, {'title': '7A Day 3', 'categories': [{'measurements': [{'value': '10.10', 'spread': '0.17', 'groupId': 'OG000'}, {'value': '10.52', 'spread': '0.34', 'groupId': 'OG001'}]}]}, {'title': '3P Day 3', 'categories': [{'measurements': [{'value': '10.32', 'spread': '0.26', 'groupId': 'OG000'}, {'value': '10.66', 'spread': '0.42', 'groupId': 'OG001'}]}]}, {'title': '11P Day 3', 'categories': [{'measurements': [{'value': '9.72', 'spread': '0.31', 'groupId': 'OG000'}, {'value': '9.94', 'spread': '0.26', 'groupId': 'OG001'}]}]}, {'title': '7A Day 4', 'categories': [{'measurements': [{'value': '10.04', 'spread': '0.33', 'groupId': 'OG000'}, {'value': '9.88', 'spread': '0.17', 'groupId': 'OG001'}]}]}, {'title': '3P Day 4', 'categories': [{'measurements': [{'value': '9.94', 'spread': '0.30', 'groupId': 'OG000'}, {'value': '9.94', 'spread': '0.23', 'groupId': 'OG001'}]}]}, {'title': '11P Day 4', 'categories': [{'measurements': [{'value': '9.54', 'spread': '0.29', 'groupId': 'OG000'}, {'value': '9.56', 'spread': '0.19', 'groupId': 'OG001'}]}]}, {'title': '7A Day 5', 'categories': [{'measurements': [{'value': '10.16', 'spread': '0.47', 'groupId': 'OG000'}, {'value': '9.64', 'spread': '0.28', 'groupId': 'OG001'}]}]}, {'title': '3P Day 5', 'categories': [{'measurements': [{'value': '10.26', 'spread': '0.38', 'groupId': 'OG000'}, {'value': '9.72', 'spread': '0.31', 'groupId': 'OG001'}]}]}, {'title': '11P Day 5', 'categories': [{'measurements': [{'value': '9.82', 'spread': '0.37', 'groupId': 'OG000'}, {'value': '9.46', 'spread': '0.23', 'groupId': 'OG001'}]}]}, {'title': '7A Day 6', 'categories': [{'measurements': [{'value': '10.18', 'spread': '0.33', 'groupId': 'OG000'}, {'value': '9.92', 'spread': '0.23', 'groupId': 'OG001'}]}]}, {'title': '3P Day 6', 'categories': [{'measurements': [{'value': '10.28', 'spread': '0.40', 'groupId': 'OG000'}, {'value': '10.28', 'spread': '0.19', 'groupId': 'OG001'}]}]}, {'title': '11P Day 6', 'categories': [{'measurements': [{'value': '9.56', 'spread': '0.37', 'groupId': 'OG000'}, {'value': '9.60', 'spread': '0.31', 'groupId': 'OG001'}]}]}, {'title': '7A Day 7', 'categories': [{'measurements': [{'value': '10.18', 'spread': '0.35', 'groupId': 'OG000'}, {'value': '9.90', 'spread': '0.17', 'groupId': 'OG001'}]}]}, {'title': '3P Day 7', 'categories': [{'measurements': [{'value': '10.02', 'spread': '0.39', 'groupId': 'OG000'}, {'value': '9.98', 'spread': '0.19', 'groupId': 'OG001'}]}]}, {'title': '11P Day 7', 'categories': [{'measurements': [{'value': '9.82', 'spread': '0.33', 'groupId': 'OG000'}, {'value': '10.03', 'spread': '0.18', 'groupId': 'OG001'}]}]}, {'title': '7A Day 8', 'categories': [{'measurements': [{'value': '10.38', 'spread': '0.31', 'groupId': 'OG000'}, {'value': '10.50', 'spread': '0.22', 'groupId': 'OG001'}]}]}, {'title': 'FOLLOW-UP', 'categories': [{'measurements': [{'value': '9.50', 'spread': '0.20', 'groupId': 'OG000'}, {'value': '9.50', 'spread': '0.12', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds to the increase over time for the PTH 2 pmol group.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete', 'description': 'mg/dl', 'unitOfMeasure': 'mg/dl', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Ionized Serum Calcium', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '4.72', 'spread': '0.10', 'groupId': 'OG000'}, {'value': '4.52', 'spread': '0.05', 'groupId': 'OG001'}]}]}, {'title': '11P Day 1', 'categories': [{'measurements': [{'value': '4.93', 'spread': '0.14', 'groupId': 'OG000'}, {'value': '4.54', 'spread': '0.18', 'groupId': 'OG001'}]}]}, {'title': '7 A Day 2', 'categories': [{'measurements': [{'value': '5.17', 'spread': '0.09', 'groupId': 'OG000'}, {'value': '5.04', 'spread': '0.11', 'groupId': 'OG001'}]}]}, {'title': '3P Day 2', 'categories': [{'measurements': [{'value': '5.08', 'spread': '0.06', 'groupId': 'OG000'}, {'value': '5.01', 'spread': '0.12', 'groupId': 'OG001'}]}]}, {'title': '11P Day 2', 'categories': [{'measurements': [{'value': '5.01', 'spread': '0.15', 'groupId': 'OG000'}, {'value': '4.97', 'spread': '0.17', 'groupId': 'OG001'}]}]}, {'title': '7A Day 3', 'categories': [{'measurements': [{'value': '5.21', 'spread': '0.19', 'groupId': 'OG000'}, {'value': '5.22', 'spread': '0.19', 'groupId': 'OG001'}]}]}, {'title': '3P Day 3', 'categories': [{'measurements': [{'value': '5.08', 'spread': '0.09', 'groupId': 'OG000'}, {'value': '5.11', 'spread': '0.20', 'groupId': 'OG001'}]}]}, {'title': '11P Day 3', 'categories': [{'measurements': [{'value': '4.80', 'spread': '0.17', 'groupId': 'OG000'}, {'value': '4.82', 'spread': '0.07', 'groupId': 'OG001'}]}]}, {'title': '7A Day 4', 'categories': [{'measurements': [{'value': '5.10', 'spread': '0.09', 'groupId': 'OG000'}, {'value': '4.90', 'spread': '0.08', 'groupId': 'OG001'}]}]}, {'title': '3P Day 4', 'categories': [{'measurements': [{'value': '4.86', 'spread': '0.17', 'groupId': 'OG000'}, {'value': '4.77', 'spread': '0.09', 'groupId': 'OG001'}]}]}, {'title': '11P Day 4', 'categories': [{'measurements': [{'value': '4.93', 'spread': '0.15', 'groupId': 'OG000'}, {'value': '4.70', 'spread': '0.06', 'groupId': 'OG001'}]}]}, {'title': '7A Day 5', 'categories': [{'measurements': [{'value': '5.18', 'spread': '0.24', 'groupId': 'OG000'}, {'value': '4.84', 'spread': '0.05', 'groupId': 'OG001'}]}]}, {'title': '3P Day 5', 'categories': [{'measurements': [{'value': '5.03', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '4.91', 'spread': '0.18', 'groupId': 'OG001'}]}]}, {'title': '11P Day 5', 'categories': [{'measurements': [{'value': '4.90', 'spread': '0.16', 'groupId': 'OG000'}, {'value': '4.68', 'spread': '0.11', 'groupId': 'OG001'}]}]}, {'title': '7A Day 6', 'categories': [{'measurements': [{'value': '5.29', 'spread': '0.20', 'groupId': 'OG000'}, {'value': '4.95', 'spread': '0.13', 'groupId': 'OG001'}]}]}, {'title': '3P Day 6', 'categories': [{'measurements': [{'value': '5.17', 'spread': '0.13', 'groupId': 'OG000'}, {'value': '4.89', 'spread': '0.08', 'groupId': 'OG001'}]}]}, {'title': '11P Day 6', 'categories': [{'measurements': [{'value': '5.02', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '4.82', 'spread': '0.14', 'groupId': 'OG001'}]}]}, {'title': '7A Day 7', 'categories': [{'measurements': [{'value': '5.20', 'spread': '0.14', 'groupId': 'OG000'}, {'value': '4.99', 'spread': '0.19', 'groupId': 'OG001'}]}]}, {'title': '3P Day 7', 'categories': [{'measurements': [{'value': '4.89', 'spread': '0.12', 'groupId': 'OG000'}, {'value': '4.88', 'spread': '0.18', 'groupId': 'OG001'}]}]}, {'title': '11P Day 7', 'categories': [{'measurements': [{'value': '5.15', 'spread': '0.19', 'groupId': 'OG000'}, {'value': '4.86', 'spread': '0.14', 'groupId': 'OG001'}]}]}, {'title': '7A Day 8', 'categories': [{'measurements': [{'value': '5.34', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '5.28', 'spread': '0.16', 'groupId': 'OG001'}]}]}, {'title': 'FOLLOW-UP', 'categories': [{'measurements': [{'value': '4.79', 'spread': '0.05', 'groupId': 'OG000'}, {'value': '4.70', 'spread': '0.12', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds to the increase over time for the PTH 2 pmol group.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete', 'description': 'mg/dl', 'unitOfMeasure': 'mg/dl', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Serum Phosphorous', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '3.51', 'spread': '0.30', 'groupId': 'OG000'}, {'value': '3.45', 'spread': '0.28', 'groupId': 'OG001'}]}]}, {'title': '11P Day 1', 'categories': [{'measurements': [{'value': '4.16', 'spread': '0.12', 'groupId': 'OG000'}, {'value': '3.78', 'spread': '0.19', 'groupId': 'OG001'}]}]}, {'title': '7 A Day 2', 'categories': [{'measurements': [{'value': '3.78', 'spread': '0.15', 'groupId': 'OG000'}, {'value': '3.68', 'spread': '0.16', 'groupId': 'OG001'}]}]}, {'title': '3P Day 2', 'categories': [{'measurements': [{'value': '3.82', 'spread': '0.15', 'groupId': 'OG000'}, {'value': '3.44', 'spread': '0.24', 'groupId': 'OG001'}]}]}, {'title': '11P Day 2', 'categories': [{'measurements': [{'value': '3.86', 'spread': '0.12', 'groupId': 'OG000'}, {'value': '3.78', 'spread': '0.11', 'groupId': 'OG001'}]}]}, {'title': '7A Day 3', 'categories': [{'measurements': [{'value': '3.68', 'spread': '0.16', 'groupId': 'OG000'}, {'value': '3.58', 'spread': '0.15', 'groupId': 'OG001'}]}]}, {'title': '3P Day 3', 'categories': [{'measurements': [{'value': '3.68', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '3.28', 'spread': '0.12', 'groupId': 'OG001'}]}]}, {'title': '11P Day 3', 'categories': [{'measurements': [{'value': '3.86', 'spread': '0.09', 'groupId': 'OG000'}, {'value': '3.60', 'spread': '0.23', 'groupId': 'OG001'}]}]}, {'title': '7A Day 4', 'categories': [{'measurements': [{'value': '3.58', 'spread': '0.17', 'groupId': 'OG000'}, {'value': '3.64', 'spread': '0.18', 'groupId': 'OG001'}]}]}, {'title': '3P Day 4', 'categories': [{'measurements': [{'value': '3.38', 'spread': '0.16', 'groupId': 'OG000'}, {'value': '3.22', 'spread': '0.16', 'groupId': 'OG001'}]}]}, {'title': '11P Day 4', 'categories': [{'measurements': [{'value': '3.76', 'spread': '0.07', 'groupId': 'OG000'}, {'value': '3.52', 'spread': '0.24', 'groupId': 'OG001'}]}]}, {'title': '7A Day 5', 'categories': [{'measurements': [{'value': '3.56', 'spread': '0.14', 'groupId': 'OG000'}, {'value': '3.72', 'spread': '0.23', 'groupId': 'OG001'}]}]}, {'title': '3P Day 5', 'categories': [{'measurements': [{'value': '3.70', 'spread': '0.20', 'groupId': 'OG000'}, {'value': '3.22', 'spread': '0.24', 'groupId': 'OG001'}]}]}, {'title': '11P Day 5', 'categories': [{'measurements': [{'value': '3.56', 'spread': '0.10', 'groupId': 'OG000'}, {'value': '3.64', 'spread': '0.21', 'groupId': 'OG001'}]}]}, {'title': '7A Day 6', 'categories': [{'measurements': [{'value': '3.86', 'spread': '0.12', 'groupId': 'OG000'}, {'value': '3.60', 'spread': '0.09', 'groupId': 'OG001'}]}]}, {'title': '3P Day 6', 'categories': [{'measurements': [{'value': '3.78', 'spread': '0.21', 'groupId': 'OG000'}, {'value': '3.03', 'spread': '0.23', 'groupId': 'OG001'}]}]}, {'title': '11P Day 6', 'categories': [{'measurements': [{'value': '3.70', 'spread': '0.16', 'groupId': 'OG000'}, {'value': '3.63', 'spread': '0.09', 'groupId': 'OG001'}]}]}, {'title': '7A Day 7', 'categories': [{'measurements': [{'value': '3.70', 'spread': '0.22', 'groupId': 'OG000'}, {'value': '3.90', 'spread': '0.18', 'groupId': 'OG001'}]}]}, {'title': '3P Day 7', 'categories': [{'measurements': [{'value': '3.12', 'spread': '0.17', 'groupId': 'OG000'}, {'value': '3.18', 'spread': '0.11', 'groupId': 'OG001'}]}]}, {'title': '11P Day 7', 'categories': [{'measurements': [{'value': '3.48', 'spread': '0.11', 'groupId': 'OG000'}, {'value': '3.55', 'spread': '0.21', 'groupId': 'OG001'}]}]}, {'title': '7A Day 8', 'categories': [{'measurements': [{'value': '3.82', 'spread': '0.19', 'groupId': 'OG000'}, {'value': '3.80', 'spread': '0.09', 'groupId': 'OG001'}]}]}, {'title': 'FOLLOW-UP', 'categories': [{'measurements': [{'value': '4.12', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '3.64', 'spread': '0.28', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '>0.05', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds to change over time for the PTH 2 and PTH 4 pmol groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete', 'description': 'mg/dl', 'unitOfMeasure': 'mg/dl', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': '1,25 Vitamin D', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '37.78', 'spread': '4.71', 'groupId': 'OG000'}, {'value': '39.18', 'spread': '5.82', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '40.90', 'spread': '2.78', 'groupId': 'OG000'}, {'value': '42.72', 'spread': '7.60', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '35.68', 'spread': '2.94', 'groupId': 'OG000'}, {'value': '41.74', 'spread': '6.39', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '27.70', 'spread': '7.57', 'groupId': 'OG000'}, {'value': '34.72', 'spread': '6.91', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '36.16', 'spread': '2.38', 'groupId': 'OG000'}, {'value': '31.53', 'spread': '4.78', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '38.00', 'spread': '3.13', 'groupId': 'OG000'}, {'value': '35.68', 'spread': '3.39', 'groupId': 'OG001'}]}]}, {'title': 'Day 7', 'categories': [{'measurements': [{'value': '32.18', 'spread': '3.41', 'groupId': 'OG000'}, {'value': '28.48', 'spread': '2.82', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '34.78', 'spread': '3.57', 'groupId': 'OG000'}, {'value': '33.13', 'spread': '3.56', 'groupId': 'OG001'}]}]}, {'title': 'follow-up', 'categories': [{'measurements': [{'value': '37.06', 'spread': '4.46', 'groupId': 'OG000'}, {'value': '40.16', 'spread': '4.46', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.01', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds to change over time for the PTH 2 and PTH 4 pmol groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, daily up to Day 8 and follow-up', 'description': 'pg/ml', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Parathyroid Hormone (1-84)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '20.90', 'spread': '3.85', 'groupId': 'OG000'}, {'value': '52.44', 'spread': '12.88', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '3.86', 'spread': '0.86', 'groupId': 'OG000'}, {'value': '5.30', 'spread': '2.11', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '3.00', 'spread': '0.00', 'groupId': 'OG000'}, {'value': '3.38', 'spread': '0.38', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '4.12', 'spread': '1.12', 'groupId': 'OG000'}, {'value': '5.00', 'spread': '2.00', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '4.64', 'spread': '1.64', 'groupId': 'OG000'}, {'value': '11.68', 'spread': '6.28', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '3.50', 'spread': '0.50', 'groupId': 'OG000'}, {'value': '6.34', 'spread': '3.73', 'groupId': 'OG001'}]}]}, {'title': 'Day 7', 'categories': [{'measurements': [{'value': '3.58', 'spread': '0.58', 'groupId': 'OG000'}, {'value': '6.68', 'spread': '3.68', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '3.09', 'spread': '0.09', 'groupId': 'OG000'}, {'value': '3.00', 'spread': '0.00', 'groupId': 'OG001'}]}]}, {'title': 'follow-up', 'categories': [{'measurements': [{'value': '23.60', 'spread': '2.29', 'groupId': 'OG000'}, {'value': '35.20', 'spread': '3.79', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<.05', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'the reported p-values correspond to the decrease compared to baseline in all arms/groups at Days 2-8', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, daily up to Day 8 and follow-up', 'description': 'pg/ml', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Fractional Excretion of Calcium', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '3.38', 'spread': '1.42', 'groupId': 'OG000'}, {'value': '1.80', 'spread': '0.41', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '2.83', 'spread': '0.27', 'groupId': 'OG000'}, {'value': '2.87', 'spread': '0.71', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '4.28', 'spread': '0.63', 'groupId': 'OG000'}, {'value': '3.76', 'spread': '0.63', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '2.82', 'spread': '0.51', 'groupId': 'OG000'}, {'value': '3.87', 'spread': '0.89', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '3.90', 'spread': '0.69', 'groupId': 'OG000'}, {'value': '2.54', 'spread': '0.42', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '4.44', 'spread': '0.57', 'groupId': 'OG000'}, {'value': '3.49', 'spread': '0.69', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '5.54', 'spread': '0.70', 'groupId': 'OG000'}, {'value': '4.58', 'spread': '0.96', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.002', 'groupIds': ['OG000'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'the reported p-value corresponds to the increase compared to baseline over time (days 2-8) in the PTH 2 pmol group', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline and daily', 'description': '% = (S Creatinine X U Calcium)/(S Calcium X U Creatinine)', 'unitOfMeasure': '% of excretion', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': '24 Hour Urine Calcium', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'categories': [{'measurements': [{'value': '315.278845', 'spread': '25.0352949', 'groupId': 'OG000'}, {'value': '210.24827', 'spread': '58.3459645', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '24 hours period from Day 7 to Day 8', 'description': 'mg/gm creatinine', 'unitOfMeasure': 'mg/gm creatinine', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Tubular Maximum for Phosphorous', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '3.80', 'spread': '0.40', 'groupId': 'OG000'}, {'value': '3.50', 'spread': '0.28', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '3.28', 'spread': '0.16', 'groupId': 'OG000'}, {'value': '3.30', 'spread': '0.13', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '3.37', 'spread': '0.20', 'groupId': 'OG000'}, {'value': '3.11', 'spread': '0.24', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '3.25', 'spread': '0.27', 'groupId': 'OG000'}, {'value': '3.66', 'spread': '0.37', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '3.19', 'spread': '0.20', 'groupId': 'OG000'}, {'value': '3.31', 'spread': '0.22', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '3.45', 'spread': '0.16', 'groupId': 'OG000'}, {'value': '3.25', 'spread': '0.17', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '3.52', 'spread': '0.34', 'groupId': 'OG000'}, {'value': '3.43', 'spread': '0.10', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.61', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds to change over time for the PTH 2 and PTH 4 pmol groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline and daily', 'description': 'mg/dl', 'unitOfMeasure': 'mg/dl', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Serum Amino-terminal of Collagen- (sNTX)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '0', 'spread': '0', 'groupId': 'OG000'}, {'value': '0', 'spread': '0', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '61.8428952', 'spread': '18.6263576', 'groupId': 'OG000'}, {'value': '77.4709521', 'spread': '13.5088219', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '85.7699521', 'spread': '27.761763', 'groupId': 'OG000'}, {'value': '85.9288044', 'spread': '12.9913176', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '96.3668762', 'spread': '29.0312368', 'groupId': 'OG000'}, {'value': '59.9595445', 'spread': '18.6508014', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '107.517148', 'spread': '29.2958519', 'groupId': 'OG000'}, {'value': '83.3701575', 'spread': '21.9993233', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '150.594712', 'spread': '38.2863053', 'groupId': 'OG000'}, {'value': '120.268081', 'spread': '17.8645936', 'groupId': 'OG001'}]}]}, {'title': 'Day 7', 'categories': [{'measurements': [{'value': '141.193285', 'spread': '28.7484727', 'groupId': 'OG000'}, {'value': '109.660098', 'spread': '30.4136118', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '153.72039', 'spread': '38.1279427', 'groupId': 'OG000'}, {'value': '148.451289', 'spread': '23.0512356', 'groupId': 'OG001'}]}]}, {'title': 'follow-up', 'categories': [{'measurements': [{'value': '4.06445076', 'spread': '8.25178671', 'groupId': 'OG000'}, {'value': '1.05486408', 'spread': '11.8266679', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<.008', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds to the % increase compared to baseline in all Arms/groups on Days 2-8', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}, {'pValue': '>0.05', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds the the % change from baseline at follow-up in all Arms/groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline', 'unitOfMeasure': '% change from baseline', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Serum Carboxy-terminal of Collagen- 1(sCTX)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '0', 'spread': '0', 'groupId': 'OG000'}, {'value': '0', 'spread': '0', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '113.70', 'spread': '37.63', 'groupId': 'OG000'}, {'value': '104.07', 'spread': '11.83', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '136.76', 'spread': '45.34', 'groupId': 'OG000'}, {'value': '112.11', 'spread': '22.41', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '142.66', 'spread': '46.55', 'groupId': 'OG000'}, {'value': '70.74', 'spread': '37.02', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '165.97', 'spread': '55.34', 'groupId': 'OG000'}, {'value': '92.13', 'spread': '36.22', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '205.39', 'spread': '60.11', 'groupId': 'OG000'}, {'value': '141.66', 'spread': '17.80', 'groupId': 'OG001'}]}]}, {'title': 'Day 7', 'categories': [{'measurements': [{'value': '206.06', 'spread': '60.02', 'groupId': 'OG000'}, {'value': '168.77', 'spread': '31.35', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '225.04', 'spread': '63.07', 'groupId': 'OG000'}, {'value': '244.50', 'spread': '25.28', 'groupId': 'OG001'}]}]}, {'title': 'follow-up', 'categories': [{'measurements': [{'value': '-6.78', 'spread': '13.40', 'groupId': 'OG000'}, {'value': '-11.82', 'spread': '17.86', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds to % change (increase) from baseline in all Arms/groups at Days 2-8.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}, {'pValue': '>0.05', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The reported p-value corresponds the the % change from baseline at follow-up in all Arms/groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline', 'unitOfMeasure': '% change from baseline', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Amino-terminal Peptides of Procollagen- 1(P1NP)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '0', 'spread': '0', 'groupId': 'OG000'}, {'value': '0', 'spread': '0', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '-18.536953', 'spread': '3.06129512', 'groupId': 'OG000'}, {'value': '-16.118573', 'spread': '9.23396676', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '-31.14427', 'spread': '3.986728', 'groupId': 'OG000'}, {'value': '-35.577655', 'spread': '3.47737847', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '-32.942391', 'spread': '1.15253446', 'groupId': 'OG000'}, {'value': '-35.018736', 'spread': '5.91933273', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '-31.506308', 'spread': '2.94297475', 'groupId': 'OG000'}, {'value': '-35.309609', 'spread': '6.61031904', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '-36.35864', 'spread': '5.71685066', 'groupId': 'OG000'}, {'value': '-35.064188', 'spread': '5.84391487', 'groupId': 'OG001'}]}]}, {'title': 'Day 7', 'categories': [{'measurements': [{'value': '-40.709396', 'spread': '5.7024817', 'groupId': 'OG000'}, {'value': '-30.58629', 'spread': '3.41615735', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '-39.046467', 'spread': '4.79183284', 'groupId': 'OG000'}, {'value': '-35.619862', 'spread': '3.18918608', 'groupId': 'OG001'}]}]}, {'title': 'follow-up', 'categories': [{'measurements': [{'value': '31.4333667', 'spread': '9.87895156', 'groupId': 'OG000'}, {'value': '26.3367446', 'spread': '16.1801142', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'the reported p-value corresponds to % decrease compared to baseline at Days 2-8 in all Arms/groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}, {'pValue': '.01', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'the reported p-value corresponds to % change from baseline at the follow-up visit in all Arms/groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'the reported p-value corresponds to % change from baseline at the follow-up visit in all Arms/groups', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline', 'unitOfMeasure': '% change from baseline', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Bone Specific Alkaline Phosphatase (BSAP)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1', 'description': 'PTH(1-34) 2 picomols (pmols)/kg/hr'}, {'id': 'OG001', 'title': 'Group 2', 'description': 'PTH(1-34) 4 picomoles/kg/hr for one week'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '0', 'spread': '0', 'groupId': 'OG000'}, {'value': '0', 'spread': '0', 'groupId': 'OG001'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '7.35', 'spread': '3.22', 'groupId': 'OG000'}, {'value': '7.91', 'spread': '7.47', 'groupId': 'OG001'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '-5.61', 'spread': '4.67', 'groupId': 'OG000'}, {'value': '9.05', 'spread': '12.82', 'groupId': 'OG001'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '4.34', 'spread': '4.85', 'groupId': 'OG000'}, {'value': '0.77', 'spread': '9.93', 'groupId': 'OG001'}]}]}, {'title': 'Day 5', 'categories': [{'measurements': [{'value': '-8.75', 'spread': '3.39', 'groupId': 'OG000'}, {'value': '-2.19', 'spread': '14.10', 'groupId': 'OG001'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '-3.42', 'spread': '15.55', 'groupId': 'OG000'}, {'value': '-8.89', 'spread': '11.60', 'groupId': 'OG001'}]}]}, {'title': 'Day 7', 'categories': [{'measurements': [{'value': '-1.35', 'spread': '12.69', 'groupId': 'OG000'}, {'value': '-13.72', 'spread': '12.96', 'groupId': 'OG001'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '2.09', 'spread': '11.94', 'groupId': 'OG000'}, {'value': '-9.91', 'spread': '16.98', 'groupId': 'OG001'}]}]}, {'title': 'follow-up', 'categories': [{'measurements': [{'value': '14.08', 'spread': '9.96', 'groupId': 'OG000'}, {'value': '5.51', 'spread': '8.28', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '>.05', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'the reported p-value corresponds to % change compared to baseline at Days 2-8 in all Arms/groups', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'statisticalComment': 'The level of statistical significance was set at .05 (two-tailed)', 'testedNonInferiority': True, 'nonInferiorityComment': 'The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline', 'unitOfMeasure': '% change from baseline', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Group 1', 'description': 'PTH (1-34) 2 picomoles (pmols)/kg/hr'}, {'id': 'FG001', 'title': 'Group 2', 'description': 'PTH (1-34) 4 picomoles (pmols)/kg/hr'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '5'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Starting in October 2006, 19 Healthy caucasian males \\& females between 24 - 35 yrs were screened. By November 2007 11 subjects were randomized and 10 completed the one week infusion study which was done on the Clinical and Translational Research Clinic (CTRC) at the University of Pittsburgh Medical Center (UPMC).', 'preAssignmentDetails': 'Candidates were non-smokers and females had negative pregnancy tests. Those on chronic medications with the exception of oral contraceptives or stable thyroid hormone replacement were excluded. Body mass index had to be less than 30, and all had normal screening labs.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Parathyroid Hormone - 2 Picomoles/kg/hr.', 'description': 'Subjects initially entering the study receive study drug Parathyroid Hormone (1-34) in intravenous doses beginning at 2 picomoles/kg/hr. Doses will be slowly and safely escalated in groups of 3 subjects.'}, {'id': 'BG001', 'title': 'Parathyroid Hormone(1-34) - 4 Picomoles/kg/hr', 'description': 'Subjects received Parathyroid Hormone (1-34)intravenously at 4 picomoles/kg/hr.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Eleven subjects received parathyroid hormone (1-34) infusions intravenously for one week.'}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 11}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2006-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-03', 'completionDateStruct': {'date': '2007-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-03-18', 'studyFirstSubmitDate': '2006-09-14', 'resultsFirstSubmitDate': '2014-04-25', 'studyFirstSubmitQcDate': '2006-09-14', 'lastUpdatePostDateStruct': {'date': '2016-03-22', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2016-03-18', 'studyFirstPostDateStruct': {'date': '2006-09-18', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-03-22', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2007-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Participants With Dose Limiting Toxicity', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days', 'description': 'DLT was defined as achieving one major criterion or two minor criteria rated at ≥ 2 on a scale of 0-5. The major criteria were defined as symptomatic orthostatic hypotension (systolic BP fall \\>30 mm/hg), tachycardia (pulse \\> 120), hypertension (systolic BP \\>160 mm/hg on 2 occasions), hypercalcemia (serum calcium ≥ 12 mg/dl), and hypophosphatemia (serum phosphorous \\< 1.5 mg/dl). Minor criteria included symptoms such as flushing, nausea, abdominal or muscle cramps, dizziness, lightheadedness, palpitations, etc.'}, {'measure': 'Total Serum Calcium', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete', 'description': 'mg/dl'}, {'measure': 'Ionized Serum Calcium', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete', 'description': 'mg/dl'}, {'measure': 'Serum Phosphorous', 'timeFrame': '12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete', 'description': 'mg/dl'}], 'secondaryOutcomes': [{'measure': '1,25 Vitamin D', 'timeFrame': 'baseline, daily up to Day 8 and follow-up', 'description': 'pg/ml'}, {'measure': 'Parathyroid Hormone (1-84)', 'timeFrame': 'baseline, daily up to Day 8 and follow-up', 'description': 'pg/ml'}, {'measure': 'Fractional Excretion of Calcium', 'timeFrame': 'baseline and daily', 'description': '% = (S Creatinine X U Calcium)/(S Calcium X U Creatinine)'}, {'measure': '24 Hour Urine Calcium', 'timeFrame': '24 hours period from Day 7 to Day 8', 'description': 'mg/gm creatinine'}, {'measure': 'Tubular Maximum for Phosphorous', 'timeFrame': 'baseline and daily', 'description': 'mg/dl'}, {'measure': 'Serum Amino-terminal of Collagen- (sNTX)', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline'}, {'measure': 'Serum Carboxy-terminal of Collagen- 1(sCTX)', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline'}, {'measure': 'Amino-terminal Peptides of Procollagen- 1(P1NP)', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline'}, {'measure': 'Bone Specific Alkaline Phosphatase (BSAP)', 'timeFrame': 'baseline, daily, one week follow-up', 'description': '% change from baseline'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Endocrine System Diseases', 'MusculoSkeletal System Disease', 'Hormone', 'Physiologic Properties'], 'conditions': ['Osteoporosis', 'Bone Diseases, Endocrine', 'Hyperparathyroidism']}, 'referencesModule': {'references': [{'pmid': '12574182', 'type': 'BACKGROUND', 'citation': 'Horwitz MJ, Tedesco MB, Gundberg C, Garcia-Ocana A, Stewart AF. Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2003 Feb;88(2):569-75. doi: 10.1210/jc.2002-021122.'}, {'pmid': '11297578', 'type': 'BACKGROUND', 'citation': 'Syed MA, Horwitz MJ, Tedesco MB, Garcia-Ocana A, Wisniewski SR, Stewart AF. Parathyroid hormone-related protein-(1--36) stimulates renal tubular calcium reabsorption in normal human volunteers: implications for the pathogenesis of humoral hypercalcemia of malignancy. J Clin Endocrinol Metab. 2001 Apr;86(4):1525-31. doi: 10.1210/jcem.86.4.7406.'}, {'pmid': '12679445', 'type': 'BACKGROUND', 'citation': 'Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocana A, Stewart AF. Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. J Clin Endocrinol Metab. 2003 Apr;88(4):1603-9. doi: 10.1210/jc.2002-020773.'}, {'pmid': '8550752', 'type': 'BACKGROUND', 'citation': 'Everhart-Caye M, Inzucchi SE, Guinness-Henry J, Mitnick MA, Stewart AF. Parathyroid hormone (PTH)-related protein(1-36) is equipotent to PTH(1-34) in humans. J Clin Endocrinol Metab. 1996 Jan;81(1):199-208. doi: 10.1210/jcem.81.1.8550752.'}, {'pmid': '9062504', 'type': 'BACKGROUND', 'citation': 'Henry JG, Mitnick M, Dann PR, Stewart AF. Parathyroid hormone-related protein-(1-36) is biologically active when administered subcutaneously to humans. J Clin Endocrinol Metab. 1997 Mar;82(3):900-6. doi: 10.1210/jcem.82.3.3811.'}, {'pmid': '9709948', 'type': 'BACKGROUND', 'citation': 'Plotkin H, Gundberg C, Mitnick M, Stewart AF. Dissociation of bone formation from resorption during 2-week treatment with human parathyroid hormone-related peptide-(1-36) in humans: potential as an anabolic therapy for osteoporosis. J Clin Endocrinol Metab. 1998 Aug;83(8):2786-91. doi: 10.1210/jcem.83.8.5047.'}, {'pmid': '10934650', 'type': 'BACKGROUND', 'citation': 'Stewart AF, Cain RL, Burr DB, Jacob D, Turner CH, Hock JM. Six-month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1-34, parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893. J Bone Miner Res. 2000 Aug;15(8):1517-25. doi: 10.1359/jbmr.2000.15.8.1517.'}, {'pmid': '16160737', 'type': 'BACKGROUND', 'citation': 'Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia-Ocana A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D. J Bone Miner Res. 2005 Oct;20(10):1792-803. doi: 10.1359/JBMR.050602. Epub 2005 Jun 6.'}, {'pmid': '16151606', 'type': 'BACKGROUND', 'citation': 'Horwitz MJ, Tedesco MB, Sereika SM, Garcia-Ocana A, Bisello A, Hollis BW, Gundberg C, Stewart AF. Safety and tolerability of subcutaneous PTHrP(1-36) in healthy human volunteers: a dose escalation study. Osteoporos Int. 2006 Feb;17(2):225-30. doi: 10.1007/s00198-005-1976-3. Epub 2005 Sep 7.'}, {'pmid': '1658941', 'type': 'BACKGROUND', 'citation': 'Juppner H, Abou-Samra AB, Freeman M, Kong XF, Schipani E, Richards J, Kolakowski LF Jr, Hock J, Potts JT Jr, Kronenberg HM, et al. A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science. 1991 Nov 15;254(5034):1024-6. doi: 10.1126/science.1658941.'}, {'pmid': '2539369', 'type': 'BACKGROUND', 'citation': 'Orloff JJ, Wu TL, Heath HW, Brady TG, Brines ML, Stewart AF. Characterization of canine renal receptors for the parathyroid hormone-like protein associated with humoral hypercalcemia of malignancy. J Biol Chem. 1989 Apr 15;264(11):6097-103.'}, {'pmid': '1327716', 'type': 'BACKGROUND', 'citation': 'Orloff JJ, Ribaudo AE, McKee RL, Rosenblatt M, Stewart AF. A pharmacological comparison of parathyroid hormone receptors in human bone and kidney. Endocrinology. 1992 Oct;131(4):1603-11. doi: 10.1210/endo.131.4.1327716.'}, {'pmid': '8345044', 'type': 'BACKGROUND', 'citation': 'Samuels MH, Veldhuis J, Cawley C, Urban RJ, Luther M, Bauer R, Mundy G. Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis. J Clin Endocrinol Metab. 1993 Aug;77(2):399-403. doi: 10.1210/jcem.77.2.8345044.'}, {'pmid': '7769133', 'type': 'BACKGROUND', 'citation': 'Prank K, Nowlan SJ, Harms HM, Kloppstech M, Brabant G, Hesch RD, Sejnowski TJ. Time series prediction of plasma hormone concentration. Evidence for differences in predictability of parathyroid hormone secretion between osteoporotic patients and normal controls. J Clin Invest. 1995 Jun;95(6):2910-9. doi: 10.1172/JCI117998.'}, {'pmid': '14638923', 'type': 'BACKGROUND', 'citation': 'Schmitt CP, Obry J, Feneberg R, Veldhuis JD, Mehls O, Ritz E, Schaefer F. Beta1-adrenergic blockade augments pulsatile PTH secretion in humans. J Am Soc Nephrol. 2003 Dec;14(12):3245-50. doi: 10.1097/01.asn.0000101240.47747.7f.'}, {'pmid': '8855835', 'type': 'BACKGROUND', 'citation': 'Chapotot F, Gronfier C, Spiegel K, Luthringer R, Brandenberger G. Relationships between intact parathyroid hormone 24-hour profiles, sleep-wake cycle, and sleep electroencephalographic activity in man. J Clin Endocrinol Metab. 1996 Oct;81(10):3759-65. doi: 10.1210/jcem.81.10.8855835.'}, {'pmid': '8288713', 'type': 'BACKGROUND', 'citation': 'Harms HM, Schlinke E, Neubauer O, Kayser C, Wustermann PR, Horn R, Kulpmann WR, von zur Muhlen A, Hesch RD. Pulse amplitude and frequency modulation of parathyroid hormone in primary hyperparathyroidism. J Clin Endocrinol Metab. 1994 Jan;78(1):53-7. doi: 10.1210/jcem.78.1.8288713.'}, {'pmid': '7593443', 'type': 'BACKGROUND', 'citation': "Ledger GA, Burritt MF, Kao PC, O'Fallon WM, Riggs BL, Khosla S. Role of parathyroid hormone in mediating nocturnal and age-related increases in bone resorption. J Clin Endocrinol Metab. 1995 Nov;80(11):3304-10. doi: 10.1210/jcem.80.11.7593443."}, {'pmid': '8989274', 'type': 'BACKGROUND', 'citation': 'el-Hajj Fuleihan G, Klerman EB, Brown EN, Choe Y, Brown EM, Czeisler CA. The parathyroid hormone circadian rhythm is truly endogenous--a general clinical research center study. J Clin Endocrinol Metab. 1997 Jan;82(1):281-6. doi: 10.1210/jcem.82.1.3683.'}, {'pmid': '7775469', 'type': 'BACKGROUND', 'citation': 'Plawner LL, Philbrick WM, Burtis WJ, Broadus AE, Stewart AF. Cell type-specific secretion of parathyroid hormone-related protein via the regulated versus the constitutive secretory pathway. J Biol Chem. 1995 Jun 9;270(23):14078-84. doi: 10.1074/jbc.270.23.14078.'}, {'pmid': '1322424', 'type': 'BACKGROUND', 'citation': 'Fraher LJ, Hodsman AB, Jonas K, Saunders D, Rose CI, Henderson JE, Hendy GN, Goltzman D. A comparison of the in vivo biochemical responses to exogenous parathyroid hormone-(1-34) [PTH-(1-34)] and PTH-related peptide-(1-34) in man. J Clin Endocrinol Metab. 1992 Aug;75(2):417-23. doi: 10.1210/jcem.75.2.1322424.'}, {'pmid': '3584110', 'type': 'BACKGROUND', 'citation': 'Burtis WJ, Wu T, Bunch C, Wysolmerski JJ, Insogna KL, Weir EC, Broadus AE, Stewart AF. Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem. 1987 May 25;262(15):7151-6.'}, {'pmid': '3619898', 'type': 'BACKGROUND', 'citation': 'Stewart AF, Wu T, Goumas D, Burtis WJ, Broadus AE. N-terminal amino acid sequence of two novel tumor-derived adenylate cyclase-stimulating proteins: identification of parathyroid hormone-like and parathyroid hormone-unlike domains. Biochem Biophys Res Commun. 1987 Jul 31;146(2):672-8. doi: 10.1016/0006-291x(87)90581-x.'}, {'pmid': '8798692', 'type': 'BACKGROUND', 'citation': 'Wu TL, Vasavada RC, Yang K, Massfelder T, Ganz M, Abbas SK, Care AD, Stewart AF. Structural and physiologic characterization of the mid-region secretory species of parathyroid hormone-related protein. J Biol Chem. 1996 Oct 4;271(40):24371-81. doi: 10.1074/jbc.271.40.24371.'}, {'pmid': '8430979', 'type': 'BACKGROUND', 'citation': 'Cosman F, Shen V, Xie F, Seibel M, Ratcliffe A, Lindsay R. Estrogen protection against bone resorbing effects of parathyroid hormone infusion. Assessment by use of biochemical markers. Ann Intern Med. 1993 Mar 1;118(5):337-43. doi: 10.7326/0003-4819-118-5-199303010-00003.'}, {'pmid': '8450043', 'type': 'BACKGROUND', 'citation': 'Hodsman AB, Fraher LJ, Ostbye T, Adachi JD, Steer BM. An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis. J Clin Invest. 1993 Mar;91(3):1138-48. doi: 10.1172/JCI116273.'}, {'pmid': '21544866', 'type': 'DERIVED', 'citation': 'Horwitz MJ, Tedesco MB, Sereika SM, Prebehala L, Gundberg CM, Hollis BW, Bisello A, Garcia-Ocana A, Carneiro RM, Stewart AF. A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover. J Bone Miner Res. 2011 Sep;26(9):2287-97. doi: 10.1002/jbmr.415.'}]}, 'descriptionModule': {'briefSummary': "Study consists of an eight day inpatient visit on the General Clinical Research Center. The investigators' specific aims are to:\n\n1. To define the maximum safe dose of a seven day continuous administration of parathyroid hormone \\[PTH(1-34)\\] in healthy human volunteers.\n2. To estimate the effect of a seven day continuous administration of parathyroid Hormone (PTH) in escalating doses on vitamin D metabolism, markers of bone turnover and fractional excretion of urine.", 'detailedDescription': 'This study will expand upon earlier infusions studies that demonstrated: 1) There is a dose-related increase in 1,25 (OH)2 vitamin D in response to PTHrP and PTH over multiple days. 2) There is a markedly attenuated vitamin D response to PTHrP compared to PTH, particularly during the second 24 hours. 3) The increase in 1,25 (OH)2 vitamin D is almost certainly responsible for the greater calcemic effect of PTH compared to PTHrP. 4) PTHrP is obviously a weaker agonist of 1,25 (OH)2 vitamin D but does not result in its suppression as is seen in Humoral Hypercalcemia of Malignancy (HHM). Thus, the suppression of 1,25 (OH)2 vitamin D seen in HHM remained unexplained. In addition to assessing the effects of an infusion of PTHrP and PTH on calcium handling and 1,25(OH)2 vitamin D, we also measured their effects on markers of bone turnover. Given the clinical observations seen in Hyperparathyroidism (HPT) and HHM, we anticipated that PTH would stimulate both bone resorption and formation, while PTHrP would stimulate bone resorption but inhibit formation. However, we observed that infusions of PTHrP and PTH resulted in an equivalent, rapid increase in bone resorption as measured by N-telopeptide (NTx) and C-telopeptide (CTx), as well as a progressive decline in bone formation. There was no difference between PTH and PTHrP. We assumed that formation would ultimately increase with additional time, as seen in HPT, and therefore examined an additional group of subjects infused with PTHrP for 96 hours. However, N-terminal propeptide of type 1 procollagen (P1NP) continued to decline even further as is seen in HHM in contrast to HPT. We have not yet studied longer infusions of PTH.\n\nOne of the reasons for doing this pilot study is to determine the optimal dosing of PTH over a week period of time. Intravenous PTH has never been infused into human beings for prolonged periods of time. The investigators question whether a prolonged continuous intravenous infusion of PTH will lead to a sustained and progressive suppression of bone formation as occurs in HHM or an increase in bone formation as occurs in HPT. They also want to assess the direct influence of long-term continuous PTH infusions on plasma 1,25 (OH)2 vitamin D regulation in healthy human volunteers. We have shown in our previous studies that doses of 8 picomoles (pmol)/kg/hr PTH given over 48 hours result in sustained mild serum hypercalcemia, with serum calcium seeming to plateau in the range of 11 - 11.5 mg/dL after 48 hours. A dose of 8 picomoles (pmol)/kg/hr has also been shown to cause desirable effects on serum 1,25(OH)2 vitamin D and markers of bone turnover, and may therefore be the "ideal" dose. However, we do not know whether serum calcium will plateau after an infusion of 48 hours with escalating doses or whether it will continue to increase over seven days.\n\nTo determine what will happen with a prolonged infusion, we plan to start with doses lower than 8 picomoles (pmol)/kg/hr, and then gradually increase the dose of PTH in successive groups of subjects. In the event of a significant adverse effect, immediate action will be taken to reverse it. Protocols will be in place to follow in the event of expected adverse events such as hypotension, nausea, and muscle cramping. Severe sudden side effects are not anticipated; however, mild easily reversible side effects are to be expected as an outcome in order to determine the optimal dose of PTH. This study has been approved by the NIH and the Data Safety Monitoring Board (DSMB).\n\nSeventy five normal healthy men and women will be screened for an eight day in-patient admission to the General Clinical Research Center (GCRC). Thirty evaluable research participants will receive a seven day infusion of a predetermined dose of PTH. Vitals signs, blood pressure, blood and urine lab results will be monitored frequently as per the study flow sheet. The starting dose of PTH, 2 picomoles (pmol)/kg, will be given to three normal healthy subjects. The dose will be escalated in increments with successive groups of three subjects each, until early adverse effects (mild hypercalcemia, postural hypotension, tachycardia) are seen. This dose will then be used in future studies. The investigators with this study are trying to discover if a prolonged continuous intravenous infusion of PTH will lead to a sustained and progressive suppression of bone formation as occurs in HHM or an increase in bone formation as occurs in HPT.\n\nSubject Population will consist of healthy young adults, ages 24-35 years, as in our other safety and physiologic studies. It is anticipated that we will need to screen 75 subjects in order to obtain 30 evaluable subjects.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '35 Years', 'minimumAge': '24 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy Caucasian, Hispanic or Asian subjects\n* Males and Females\n* Non-smoker\n* Ages 24 - 35 years old\n* Subjects will be recruited either from the employee pool of the University of Pittsburgh or the University of Pittsburgh Medical Center (UPMC), or the general population living in the vicinity.\n* Participation in this study by an employee or a potential employee at the University of Pittsburgh or UPMC has no effect on their employment or potential employment.\n* Participants in the study will be required to discontinue all vitamins and health food supplements two weeks prior to the study.\n\nExclusion Criteria:\n\n* Cardiac, hypertensive, vascular, renal (serum creatinine of \\>1.5), pulmonary, endocrine, musculoskeletal, hepatic, hematologic or malignant or rheumatologic disease\n* Body Mass Index (BMI) \\> 30,\n* Anemia (hematocrit less than 36% in women, less than 40% in men),\n* Pregnancy (all women will have a urine pregnancy test performed immediately before starting the study and must not be pregnant)\n* Significant alcohol or drug abuse or\n* Baseline hypotension (systolic blood pressure less than 90 mm/Hg).\n* Subjects will be excluded for abnormal levels of any of the screening labs including: ionized and total serum calcium, phosphorus, creatinine, albumin, 25-hydroxyvitamin D, and PTH. Pregnancy\n* Subjects taking any chronic medications except oral contraceptives and stable doses of thyroid hormone, or those who have received any investigational drug in past 90 days will be excluded from the study.\n* Subjects may not participate in this study more than once.\n* Any subject who has previously received PTH or PTHrP, a related peptide, may not participate in this study.\n\nMinority Inclusion/Exclusion Statement: We will not include African-Americans because this group has been demonstrated by a number of investigators to display resistance to PTH, and may create wider statistical variation and a need for larger numbers of study subjects per group.'}, 'identificationModule': {'nctId': 'NCT00377312', 'briefTitle': '7 Day Continuous Parathyroid Hormone IV Infusion', 'organization': {'class': 'OTHER', 'fullName': 'University of Pittsburgh'}, 'officialTitle': 'Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone(1-34): Effects on Bone Formation', 'orgStudyIdInfo': {'id': '0606127'}, 'secondaryIdInfos': [{'id': 'R01DK073039', 'link': 'https://reporter.nih.gov/quickSearch/R01DK073039', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group 1', 'description': 'Parathyroid Hormone (PTH) (1-34) 2 picomols/kg/hr for one week.', 'interventionNames': ['Drug: Parathyroid Hormone (1-34)']}, {'type': 'EXPERIMENTAL', 'label': 'Group 2', 'description': 'Parathyroid Hormone (PTH) (1-34)4 picomols/kg/hr for one week.', 'interventionNames': ['Drug: Parathyroid Hormone (1-34)']}], 'interventions': [{'name': 'Parathyroid Hormone (1-34)', 'type': 'DRUG', 'otherNames': ['IND 60,979'], 'description': 'PTH(1-34) IV given over a one week period', 'armGroupLabels': ['Group 1', 'Group 2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '15213', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pittsburgh Medical Center', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}], 'overallOfficials': [{'name': 'Mara J. Horwitz, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Pittsburgh'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Pittsburgh', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Medicne', 'investigatorFullName': 'Mara Horwitz', 'investigatorAffiliation': 'University of Pittsburgh'}}}}