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

October 24, 2017 updated by: USWM, LLC (dba US WorldMeds)

A Phase 1 Study to Evaluate the Relative Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction

The purpose of this study is to evaluate the relative exposures of lofexidine and its major metabolites in subjects seeking buprenorphine dose reduction.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kansas
      • Overland Park, Kansas, United States, 66212

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: lofexidine with tapering buprenorphine
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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 Measures

Outcome Measure
Measure Description
Time Frame
Modified Clinical Global Impression - subject and observer
Time Frame: 3.5 hours post-8 AM dose on Days 1-7
3.5 hours post-8 AM dose on Days 1-7
Visual Analog Scale for Efficacy
Time Frame: 3.5 hours post-8 AM dose on Days 1-7
3.5 hours post-8 AM dose on Days 1-7
Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8
Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8
Holter ECGs
Time Frame: Day -1; pre-1 PM dose, 3 and 4 hours post-1 PM dose on Days 1 and 6
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)
Time Frame: screening; Day -1; within 30 minutes before every dose Days 1-8
screening; Day -1; within 30 minutes before every dose Days 1-8
Laboratory Assessments
Time Frame: screening
Measurements in hematology, chemistry, urinalysis, infectious disease panel. Labs will be done at screening.
screening
Oral temperature and respiration
Time Frame: screening; Day -1; pre-8 AM dose on Days 1-8
screening; Day -1; pre-8 AM dose on Days 1-8
12-Lead ECG
Time Frame: screening
screening
Adverse Events Assessment
Time Frame: Day -1; Days 1-8
Day -1; Days 1-8
Urine drug screening
Time Frame: Screening; Day -1, Days 1-8
Screening; Day -1, Days 1-8
Concomitant medications
Time Frame: Screening; Day -1, Days 1-8
Screening; Day -1, Days 1-8
Physical exam
Time Frame: screening; Day -1; Day 8
screening; Day -1; Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

USWM, LLC (dba US WorldMeds)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2016

Primary Completion (ACTUAL)

August 1, 2016

Study Completion (ACTUAL)

August 1, 2016

Study Registration Dates

First Submitted

June 10, 2016

First Submitted That Met QC Criteria

June 10, 2016

First Posted (ESTIMATE)

June 15, 2016

Study Record Updates

Last Update Posted (ACTUAL)

October 26, 2017

Last Update Submitted That Met QC Criteria

October 24, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • USWM- LX1-1013

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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