Study to Evaluate the Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction

NCT02801357 | Completed Phase 1

• 1 other identifier: USWM- LX1-1013
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Substance Withdrawal Syndrome; Opiate Addiction; Opiate Dependence

Keywords

substance withdrawal syndrome; opiate addiction; opiate dependence; opioid withdrawal syndrome; buprenorphine

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (12)

• Modified Clinical Global Impression - subject and observer

  3.5 hours post-8 AM dose on Days 1-7

• Visual Analog Scale for Efficacy

  3.5 hours post-8 AM dose on Days 1-7

• Columbia Suicide Severity Rating Scale (C-SSRS)

  Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8

• Holter ECGs

  Day -1; pre-1 PM dose, 3 and 4 hours post-1 PM dose on Days 1 and 6

• Blood pressure and pulse (sitting and standing)

  screening; Day -1; within 30 minutes before every dose Days 1-8

Study Arms (1)

lofexidine with tapering buprenorphine

EXPERIMENTAL

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.

Drug: lofexidine administration in subjects seeking buprenorphine dose reduction

Interventions

lofexidine administration in subjects seeking buprenorphine dose reduction DRUG

lofexidine with tapering buprenorphine

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• USWM, LLC (dba US WorldMeds): lead

Study Sites (1)

Unknown Facility

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Substance Withdrawal Syndrome; Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Narcotic-Related Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2016
• First Posted: June 15, 2016
• Study Start: June 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 26, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)