Ignite Creation Date:
2025-12-24 @ 10:32 PM
Ignite Modification Date:
2025-12-25 @ 8:05 PM
Study NCT ID:
NCT02269735
Status:
COMPLETED
Last Update Posted:
2019-01-15
First Post:
2014-10-16
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Three-part Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Healthy Participants (Part I) and Participants With Type 1 Diabetes Mellitus (Parts II and III) (MK-2640-001)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['United States']}, 'conditionBrowseModule': {'meshes': [{'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000628736', 'term': 'MK-2640'}, {'id': 'D007328', 'term': 'Insulin'}, {'id': 'D005947', 'term': 'Glucose'}, {'id': 'D061267', 'term': 'Insulin Aspart'}], 'ancestors': [{'id': 'D011384', 'term': 'Proinsulin'}, {'id': 'D061385', 'term': 'Insulins'}, {'id': 'D010187', 'term': 'Pancreatic Hormones'}, {'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'}, {'id': 'D006601', 'term': 'Hexoses'}, {'id': 'D009005', 'term': 'Monosaccharides'}, {'id': 'D000073893', 'term': 'Sugars'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D061266', 'term': 'Insulin, Short-Acting'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 74}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-11-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-01', 'completionDateStruct': {'date': '2016-07-29', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-01-11', 'studyFirstSubmitDate': '2014-10-16', 'studyFirstSubmitQcDate': '2014-10-20', 'lastUpdatePostDateStruct': {'date': '2019-01-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-10-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-07-29', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of participants who experienced an adverse event', 'timeFrame': 'Up to 30 days following last dose'}, {'measure': 'Pharmacokinetic parameter: steady state plasma concentration (Css)', 'timeFrame': 'Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval'}, {'measure': 'Pharmacokinetic parameter: area under the plasma concentration curve from time 0 to infinity (AUC [0 to infinity])', 'timeFrame': 'Part I: 18 time points between predose and 600 minutes (min.); Part II: 19 time points between predose and 535 min.; Part III: 18 time points between predose and 415 min. following start of infusion'}, {'measure': 'Pharmacokinetic parameter: clearance (CL)', 'timeFrame': 'Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval'}, {'measure': 'Pharmacokinetic parameter: volume of distribution (Vd)', 'timeFrame': 'Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval'}, {'measure': 'Pharmacokinetic parameter: plasma apparent terminal half-life', 'timeFrame': 'Part II: following 9 hour infusion; Part III: following 7 hour infusion'}, {'measure': 'Pharmacodynamic parameter: steady-state glucose infusion-rate (GIR) in Part II', 'timeFrame': 'Part II: during the final 60 minutes of the infusion'}, {'measure': 'Number of participants who discontinued study drug due to an adverse event', 'timeFrame': 'Part I: 1 day; Parts II and III: 9 days'}], 'secondaryOutcomes': [{'measure': 'Number of participants with anti-drug antibody (ADA) formation', 'timeFrame': 'Up to 30 days following last dose'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Type 1 Diabetes Mellitus']}, 'referencesModule': {'references': [{'pmid': '30125349', 'type': 'RESULT', 'citation': 'Krug AW, Visser SAG, Tsai K, Kandala B, Fancourt C, Thornton B, Morrow L, Kaarsholm NC, Bernstein HS, Stoch SA, Crutchlow M, Kelley DE, Iwamoto M. Clinical Evaluation of MK-2640: An Insulin Analog With Glucose-Responsive Properties. Clin Pharmacol Ther. 2019 Feb;105(2):417-425. doi: 10.1002/cpt.1215. Epub 2018 Sep 30.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of Part I of this study is to evaluate the safety and tolerability of intravenous (IV) doses of MK-2640 in healthy participants and to obtain preliminary plasma pharmacokinetic profiles of MK-2640. The purpose of Parts II and III of this study is to evaluate the safety and tolerability of IV doses of MK-2640 and regular human insulin (RHI), and to evaluate the pharmacokinetic and pharmacodynamic profile of MK-2640 and RHI in participants with type 1 diabetes mellitus (T1DM). Part II will be initiated only if Part I general safety, tolerability and other observed data are supportive of progression to Part II. Part III will be initiated only if Parts I and II general safety, tolerability and other observed data are supportive of progression to Part III.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria (Part I):\n\n* healthy male or healthy female of non-child bearing potential\n* in good health\n* is a non-smoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months\n\nInclusion Criteria (Parts II and III):\n\n* male or female of non-child bearing potential\n* has T1DM for at least 12 months\n* on stable doses of insulin\n* in good health\n* is a nonsmoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months\n\nExclusion Criteria:\n\n* is mentally or legally incapacitated, or has significant emotional problems at the time of screening visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years\n* has a history of clinically significant endocrine (except T1DM for Part II subjects), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases\n* is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)\n* has a history of cancer (malignancy), except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix\n* has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food, had major surgery, donated or lost 1 unit of blood within 4 weeks prior to the screening visit\n* has participated in another investigational trial within 4 weeks prior to the screening visit\n* is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of trial drug, throughout the trial, until the posttrial visit\n* consumes greater than 3 glasses of alcoholic beverages daily\n* consumes greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.\n* is currently a regular or recreational user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months\n\nExclusion Criteria (Parts II and III):\n\n* has a history of diabetic ketoacidosis in the last 6 months.\n* has had one or more severe hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness within 2 weeks prior to dosing\n* has used systemic (intravenous, oral, inhaled) glucocorticoids within 3 months of screening or is anticipated to require treatment with systemic glucocorticoids during study participation\n* has a history of hypersensitivity to pharmacologic insulins or to any of the inactive ingredients in regular human insulin, or to any E. coli-derived drug product'}, 'identificationModule': {'nctId': 'NCT02269735', 'briefTitle': 'A Three-part Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Healthy Participants (Part I) and Participants With Type 1 Diabetes Mellitus (Parts II and III) (MK-2640-001)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck Sharp & Dohme LLC'}, 'officialTitle': 'A Three-part Study Parts I, II and III: Rising Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Healthy Subjects (Part I) and Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Subjects With Type 1 Diabetes Mellitus (Part II and Part III).', 'orgStudyIdInfo': {'id': '2640-001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Part I: MK-2640 (Panel A)', 'description': 'Part I: Lowest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.', 'interventionNames': ['Drug: MK-2640', 'Drug: Dextrose', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part I: MK-2640 (Panel B)', 'description': 'Part I: Low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.', 'interventionNames': ['Drug: MK-2640', 'Drug: Dextrose', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part I: MK-2640 (Panel C)', 'description': 'Part I: Medium-low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.', 'interventionNames': ['Drug: MK-2640', 'Drug: Dextrose', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part I: MK-2640 (Panel D)', 'description': 'Part I: Medium dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.', 'interventionNames': ['Drug: MK-2640', 'Drug: Dextrose', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part I: MK-2640 (Panel E)', 'description': 'Part I: Medium-high dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.', 'interventionNames': ['Drug: MK-2640', 'Drug: Dextrose', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part I: MK-2640 (Panel F)', 'description': 'Part I: High dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.', 'interventionNames': ['Drug: MK-2640', 'Drug: Dextrose', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part I: MK-2640 (Panel G)', 'description': 'Part 1: Highest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.', 'interventionNames': ['Drug: MK-2640', 'Drug: Dextrose', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part II: MK-2640 followed by RHI', 'description': 'Part II: MK-2640 infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.', 'interventionNames': ['Drug: MK-2640', 'Biological: Regular Human Insulin (RHI)', 'Drug: Dextrose', 'Biological: Insulin aspart', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part II: RHI followed by MK-2640', 'description': 'Part II: RHI infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.', 'interventionNames': ['Drug: MK-2640', 'Biological: Regular Human Insulin (RHI)', 'Drug: Dextrose', 'Biological: Insulin aspart', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part III: MK-2640 followed by RHI', 'description': 'Part III: MK-2640 infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.', 'interventionNames': ['Drug: MK-2640', 'Biological: Regular Human Insulin (RHI)', 'Drug: Dextrose', 'Biological: Insulin aspart', 'Drug: Rescue medication']}, {'type': 'EXPERIMENTAL', 'label': 'Part III: RHI followed by MK-2640', 'description': 'Part III: RHI infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.', 'interventionNames': ['Drug: MK-2640', 'Biological: Regular Human Insulin (RHI)', 'Drug: Dextrose', 'Biological: Insulin aspart', 'Drug: Rescue medication']}], 'interventions': [{'name': 'MK-2640', 'type': 'DRUG', 'description': 'MK-2640 intravenous infusion administered to participant in a fasted state', 'armGroupLabels': ['Part I: MK-2640 (Panel A)', 'Part I: MK-2640 (Panel B)', 'Part I: MK-2640 (Panel C)', 'Part I: MK-2640 (Panel D)', 'Part I: MK-2640 (Panel E)', 'Part I: MK-2640 (Panel F)', 'Part I: MK-2640 (Panel G)', 'Part II: MK-2640 followed by RHI', 'Part II: RHI followed by MK-2640', 'Part III: MK-2640 followed by RHI', 'Part III: RHI followed by MK-2640']}, {'name': 'Regular Human Insulin (RHI)', 'type': 'BIOLOGICAL', 'description': 'RHI 100 units/mL intravenous infusion to maintain target glycemic level', 'armGroupLabels': ['Part II: MK-2640 followed by RHI', 'Part II: RHI followed by MK-2640', 'Part III: MK-2640 followed by RHI', 'Part III: RHI followed by MK-2640']}, {'name': 'Dextrose', 'type': 'DRUG', 'description': 'Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level', 'armGroupLabels': ['Part I: MK-2640 (Panel A)', 'Part I: MK-2640 (Panel B)', 'Part I: MK-2640 (Panel C)', 'Part I: MK-2640 (Panel D)', 'Part I: MK-2640 (Panel E)', 'Part I: MK-2640 (Panel F)', 'Part I: MK-2640 (Panel G)', 'Part II: MK-2640 followed by RHI', 'Part II: RHI followed by MK-2640', 'Part III: MK-2640 followed by RHI', 'Part III: RHI followed by MK-2640']}, {'name': 'Insulin aspart', 'type': 'BIOLOGICAL', 'description': 'Insulin aspart subcutaneous injection or intravenous infusion the evening before each period in Parts II and III to achieve/maintain glycemic target.', 'armGroupLabels': ['Part II: MK-2640 followed by RHI', 'Part II: RHI followed by MK-2640', 'Part III: MK-2640 followed by RHI', 'Part III: RHI followed by MK-2640']}, {'name': 'Rescue medication', 'type': 'DRUG', 'description': 'Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.', 'armGroupLabels': ['Part I: MK-2640 (Panel A)', 'Part I: MK-2640 (Panel B)', 'Part I: MK-2640 (Panel C)', 'Part I: MK-2640 (Panel D)', 'Part I: MK-2640 (Panel E)', 'Part I: MK-2640 (Panel F)', 'Part I: MK-2640 (Panel G)', 'Part II: MK-2640 followed by RHI', 'Part II: RHI followed by MK-2640', 'Part III: MK-2640 followed by RHI', 'Part III: RHI followed by MK-2640']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Medical Director', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Merck Sharp & Dohme LLC'}]}, 'ipdSharingStatementModule': {'url': 'http://engagezone.msd.com/ds_documentation.php', 'ipdSharing': 'YES', 'description': 'http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}