Ignite Creation Date:
2025-12-24 @ 7:33 PM
Ignite Modification Date:
2026-01-11 @ 4:48 AM
Study NCT ID:
NCT02313103
Status:
COMPLETED
Last Update Posted:
2017-10-26
First Post:
2014-12-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects
Sponsor:
USWM, LLC (dba US WorldMeds)
Organization:
Study Overview
Official Title:
Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects
Status:
COMPLETED
Status Verified Date:
2017-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a phase 1, open-label, parallel-group, single-dose study of lofexidine in 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function, recruited as 1:1 matches to each ESRD subjects, matched for gender, age, and BMI.
Detailed Description:
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function (creatinine \[Cr\] clearance \>90 mL/min), recruited as 1:1 matches to each ESRD subject, matched for gender, age (±10 years), and body mass index (BMI) (±15%). Normal renal function and ESRD subjects will be confined to an inpatient facility from the day before dosing to 144 or 156 hours after dosing, respectively, for a total of 7 8 nights and 8-9 days of inpatient confinement.
Subjects who successfully complete screening will report to the inpatient facility at an appropriate time the day before study drug administration to undergo pre-dosing study procedures (Day 1). The next morning (Day 1), all subjects will receive breakfast (approximately 6 hours before planned lofexidine dosing) and then ESRD subjects will begin their hemodialysis session. All subjects will receive a single, oral dose of 400 µg lofexidine HCl (two 200 µg tablets), dosed with 240 mL of water, the clock time for which will be approximately the same for both normal renal function subjects and ESRD subjects. Because ESRD subjects will be maintained on 3 times per week dialysis, lofexidine will be administered near the beginning of a 3-day between-dialysis interval.
Fingerprick blood samples for subjects with normal renal function will be collected for PK analysis at multiple time points over the next 144 hours. Fingerprick blood samples for ESRD subjects will be collected for PK analysis at multiple time points over the next 156 hours. Fingerprick blood samples (0.5 mL each) will be collected in BD Microtainer pink top K2EDTA tubes.
Two (2) venous blood samples (4-6 mL each in K2EDTA tubes) will be collected from each subject for lofexidine protein binding analysis, one sample collected 0-60 minutes before dosing and one sample collected 4 hours post-dose.
Pooled urine samples for subjects with normal renal function will be collected at 0 3 hours, 3 6 hours, 6 12 hours, 12 24 hours, 24 48 hours, 48 72 hours, 72 96 hours, and 96 144 hours post-dose. Pooled urine samples will be collected from ESRD subjects as available according to the same schedule.
Arterial and venous blood samples from the arterial-venous (A-V) shunt (0.5 mL in BD Microtainer pink top K2EDTA tubes) for PK analysis will be collected from ESRD subjects at 0.5, 1.5, 2.5, and 3.5 hours into each of the two 4 hour hemodialysis sessions. Additionally, fingerprick blood samples (0.5 mL) will be collected from the hand contralateral to the arm used for the dialysis A V shunt at each of these specified time points. Dialysate from ESRD subjects will be collected during the two 4 hour hemodialysis sessions at 0 1 hour, 1 2 hour, 2 3 hour, and 3 4 hour. Two 10 mL samples from each of the 1-hour pooled dialysate collections will be aliquoted into suitable collection tubes.
Safety will be assessed by recording adverse events (AEs), measuring vital signs (blood pressure and pulse rate) and clinical laboratory tests (chemistry, hematology, and urinalysis), recording 12 lead safety and Holter electrocardiograms (ECGs), and performing physical exams.
Subjects who successfully complete screening will report to the inpatient facility at an appropriate time the day before study drug administration to undergo pre-dosing study procedures (Day 1). The next morning (Day 1), all subjects will receive breakfast (approximately 6 hours before planned lofexidine dosing) and then ESRD subjects will begin their hemodialysis session. All subjects will receive a single, oral dose of 400 µg lofexidine HCl (two 200 µg tablets), dosed with 240 mL of water, the clock time for which will be approximately the same for both normal renal function subjects and ESRD subjects. Because ESRD subjects will be maintained on 3 times per week dialysis, lofexidine will be administered near the beginning of a 3-day between-dialysis interval.
Fingerprick blood samples for subjects with normal renal function will be collected for PK analysis at multiple time points over the next 144 hours. Fingerprick blood samples for ESRD subjects will be collected for PK analysis at multiple time points over the next 156 hours. Fingerprick blood samples (0.5 mL each) will be collected in BD Microtainer pink top K2EDTA tubes.
Two (2) venous blood samples (4-6 mL each in K2EDTA tubes) will be collected from each subject for lofexidine protein binding analysis, one sample collected 0-60 minutes before dosing and one sample collected 4 hours post-dose.
Pooled urine samples for subjects with normal renal function will be collected at 0 3 hours, 3 6 hours, 6 12 hours, 12 24 hours, 24 48 hours, 48 72 hours, 72 96 hours, and 96 144 hours post-dose. Pooled urine samples will be collected from ESRD subjects as available according to the same schedule.
Arterial and venous blood samples from the arterial-venous (A-V) shunt (0.5 mL in BD Microtainer pink top K2EDTA tubes) for PK analysis will be collected from ESRD subjects at 0.5, 1.5, 2.5, and 3.5 hours into each of the two 4 hour hemodialysis sessions. Additionally, fingerprick blood samples (0.5 mL) will be collected from the hand contralateral to the arm used for the dialysis A V shunt at each of these specified time points. Dialysate from ESRD subjects will be collected during the two 4 hour hemodialysis sessions at 0 1 hour, 1 2 hour, 2 3 hour, and 3 4 hour. Two 10 mL samples from each of the 1-hour pooled dialysate collections will be aliquoted into suitable collection tubes.
Safety will be assessed by recording adverse events (AEs), measuring vital signs (blood pressure and pulse rate) and clinical laboratory tests (chemistry, hematology, and urinalysis), recording 12 lead safety and Holter electrocardiograms (ECGs), and performing physical exams.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 1R01DA030916 | OTHER_GRANT | National Institute on Drug Abuse | View |