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

Opiate Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02801357
• Other study ID #: USWM- LX1-1013
• Status: Completed
• Phase: Phase 1
• First received: June 10, 2016
• Last updated: October 24, 2017
• Start date: June 2016
• Est. completion date: August 2016

Study information

• Verified date: October 2017
• Source: US WorldMeds LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Behavior, Addictive
• Opiate Addiction
• Opiate Dependence
• Opioid-Related Disorders
• Substance Withdrawal Syndrome
• Syndrome

Intervention

Drug:
• lofexidine administration in subjects seeking buprenorphine dose reduction

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
US WorldMeds LLC

Country where clinical trial is conducted

United States, 

Outcome

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