Back to resultsStudy to Evaluate the Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
Primary Purpose
Substance Withdrawal Syndrome, Opiate Addiction, Opiate Dependence
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
lofexidine administration in subjects seeking buprenorphine dose reduction
Sponsored by
About this trial
This is an interventional treatment trial for Substance Withdrawal Syndrome focused on measuring substance withdrawal syndrome, opiate addiction, opiate dependence, opioid withdrawal syndrome, buprenorphine
Eligibility Criteria
Inclusion Criteria:
- Have current dependency such that the subject is maintained on a daily dose between 8 and 24 mg of buprenorphine and is seeking reduction of their buprenorphine dose by at least 4 mg.
- Urine toxicology screen positive for buprenorphine at Screening.
- Agree to collection of blood samples for genotyping of CYP2D6 metabolizer status.
- If female and of childbearing potential, subject must have been using birth control for at least 30 days and must agree to use an acceptable form of birth control through at least 30 days after the last dose of study drug.
- If male, must agree to use an acceptable form of birth control throughout the entire study period and for 90 days after the last dose of study drug. Must not donate sperm for 90 days after the last dose of study drug.
Exclusion Criteria:
- Be a female subject who is pregnant or lactating.
- Have a very serious medical illness not under control.
- Have participated in an investigational drug study within the past 30 days.
- Received any drugs that are known strong, moderate or weak inhibitors of cytochrome P450 (CYP) enzymes CYP1A2, CYP2C19, or CYP2D6, within 14 days or 5 half-lives (whichever is more) before Day -1.
- Abnormal cardiovascular exam at Screening.
- Subjects requiring the following will be excluded: Tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives; Beta-receptor blockers, to avoid the risk of excessive bradycardia.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
lofexidine with tapering buprenorphine
Arm Description
Enrolled subjects must be on a daily dose of between 8 - 24 mg of buprenorphine for at least 30 days. Once enrolled, subjects will receive lofexidine as follows: Days 1 through 3, 0.6 mg 4 times daily (QID; 2.4 mg daily); Days 4 through 6, 0.8 mg QID (3.2 mg daily), and Day 7 0.8 mg at 8 AM. Subjects will take their scheduled lofexidine doses at approximately 8 AM, 1 PM, 6 PM and 11 PM. Subjects will also reduce their current buprenorphine dose by at least 4 mg on Day 1.
Outcomes
Primary Outcome Measures
Predose and peak metabolite (N-[2- aminoethyl-2-[2,6-dichlorophenoxy] propanamide [LADP], 2-[2,6-dichlorophenoxy] propionic acid [LDPA] and 2,6-Dichlorophenol [2,6-DCP]) plasma concentration to lofexidine (parent) ratios on each day of treatment
Secondary Outcome Measures
Modified Clinical Global Impression - subject and observer
Visual Analog Scale for Efficacy
Columbia Suicide Severity Rating Scale (C-SSRS)
Holter ECGs
Blood pressure and pulse (sitting and standing)
Laboratory Assessments
Measurements in hematology, chemistry, urinalysis, infectious disease panel. Labs will be done at screening.
Oral temperature and respiration
12-Lead ECG
Adverse Events Assessment
Urine drug screening
Concomitant medications
Physical exam
Full Information
NCT ID
NCT02801357
First Posted
June 10, 2016
Last Updated
October 24, 2017
Sponsor
USWM, LLC (dba US WorldMeds)
1. Study Identification
Unique Protocol Identification Number
NCT02801357
Brief Title
Study to Evaluate the Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
Official Title
A Phase 1 Study to Evaluate the Relative Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
USWM, LLC (dba US WorldMeds)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the relative exposures of lofexidine and its major metabolites in subjects seeking buprenorphine dose reduction.
Detailed Description
This is a Phase 1, open-label, inpatient study in male and female subjects seeking at least a 4 mg reduction of their buprenorphine maintenance dose. The purpose of this study is to assess the relative exposures of lofexidine and its 3 major metabolites in subjects tapering from buprenorphine maintenance treatment. Lofexidine is an alpha-2 adrenergic agonist under development for the treatment of acute withdrawal from short-acting opioids.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Substance Withdrawal Syndrome, Opiate Addiction, Opiate Dependence
Keywords
substance withdrawal syndrome, opiate addiction, opiate dependence, opioid withdrawal syndrome, buprenorphine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
lofexidine with tapering buprenorphine
Arm Type
Experimental
Arm Description
Enrolled subjects must be on a daily dose of between 8 - 24 mg of buprenorphine for at least 30 days. Once enrolled, subjects will receive lofexidine as follows: Days 1 through 3, 0.6 mg 4 times daily (QID; 2.4 mg daily); Days 4 through 6, 0.8 mg QID (3.2 mg daily), and Day 7 0.8 mg at 8 AM. Subjects will take their scheduled lofexidine doses at approximately 8 AM, 1 PM, 6 PM and 11 PM. Subjects will also reduce their current buprenorphine dose by at least 4 mg on Day 1.
Intervention Type
Drug
Intervention Name(s)
lofexidine administration in subjects seeking buprenorphine dose reduction
Primary Outcome Measure Information:
Title
Predose and peak metabolite (N-[2- aminoethyl-2-[2,6-dichlorophenoxy] propanamide [LADP], 2-[2,6-dichlorophenoxy] propionic acid [LDPA] and 2,6-Dichlorophenol [2,6-DCP]) plasma concentration to lofexidine (parent) ratios on each day of treatment
Time Frame
pre-1 PM dose and 3 hours post-1 PM dose on Days 1-6; pre-8 AM dose and 1, 3, 7, 12, 24, and 34 hours post-8 AM dose on Day 7
Secondary Outcome Measure Information:
Title
Modified Clinical Global Impression - subject and observer
Time Frame
3.5 hours post-8 AM dose on Days 1-7
Title
Visual Analog Scale for Efficacy
Time Frame
3.5 hours post-8 AM dose on Days 1-7
Title
Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame
Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8
Title
Holter ECGs
Time Frame
Day -1; pre-1 PM dose, 3 and 4 hours post-1 PM dose on Days 1 and 6
Title
Blood pressure and pulse (sitting and standing)
Time Frame
screening; Day -1; within 30 minutes before every dose Days 1-8
Title
Laboratory Assessments
Description
Measurements in hematology, chemistry, urinalysis, infectious disease panel. Labs will be done at screening.
Time Frame
screening
Title
Oral temperature and respiration
Time Frame
screening; Day -1; pre-8 AM dose on Days 1-8
Title
12-Lead ECG
Time Frame
screening
Title
Adverse Events Assessment
Time Frame
Day -1; Days 1-8
Title
Urine drug screening
Time Frame
Screening; Day -1, Days 1-8
Title
Concomitant medications
Time Frame
Screening; Day -1, Days 1-8
Title
Physical exam
Time Frame
screening; Day -1; Day 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have current dependency such that the subject is maintained on a daily dose between 8 and 24 mg of buprenorphine and is seeking reduction of their buprenorphine dose by at least 4 mg.
Urine toxicology screen positive for buprenorphine at Screening.
Agree to collection of blood samples for genotyping of CYP2D6 metabolizer status.
If female and of childbearing potential, subject must have been using birth control for at least 30 days and must agree to use an acceptable form of birth control through at least 30 days after the last dose of study drug.
If male, must agree to use an acceptable form of birth control throughout the entire study period and for 90 days after the last dose of study drug. Must not donate sperm for 90 days after the last dose of study drug.
Exclusion Criteria:
Be a female subject who is pregnant or lactating.
Have a very serious medical illness not under control.
Have participated in an investigational drug study within the past 30 days.
Received any drugs that are known strong, moderate or weak inhibitors of cytochrome P450 (CYP) enzymes CYP1A2, CYP2C19, or CYP2D6, within 14 days or 5 half-lives (whichever is more) before Day -1.
Abnormal cardiovascular exam at Screening.
Subjects requiring the following will be excluded: Tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives; Beta-receptor blockers, to avoid the risk of excessive bradycardia.
Facility Information:
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Evaluate the Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
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