Clinical trial NCT02801357: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Substance Withdrawal Syndrome
Opiate Addiction
Opiate Dependence
Keywords: substance withdrawal syndrome
opiate addiction
opiate dependence
opioid withdrawal syndrome
buprenorphine
Lead sponsor: USWM, LLC (dba US WorldMeds)
Sponsor class: INDUSTRY
First posted: 2016-06-15
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: 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:
measure: Modified Clinical Global Impression - subject and observer
timeFrame: 3.5 hours post-8 AM dose on Days 1-7
measure: Visual Analog Scale for Efficacy
timeFrame: 3.5 hours post-8 AM dose on Days 1-7
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8
measure: Holter ECGs
timeFrame: Day -1; pre-1 PM dose, 3 and 4 hours post-1 PM dose on Days 1 and 6
measure: Blood pressure and pulse (sitting and standing)
timeFrame: screening; Day -1; within 30 minutes before every dose Days 1-8
measure: Laboratory Assessments
timeFrame: screening
measure: Oral temperature and respiration
timeFrame: screening; Day -1; pre-8 AM dose on Days 1-8
measure: 12-Lead ECG
timeFrame: screening
measure: Adverse Events Assessment
timeFrame: Day -1; Days 1-8
measure: Urine drug screening
timeFrame: Screening; Day -1, Days 1-8
measure: Concomitant medications
timeFrame: Screening; Day -1, Days 1-8
measure: Physical exam
timeFrame: screening; Day -1; Day 8
Other outcomes:
Locations:
city: Overland Park
country: United States
state: Kansas
Study officials:
References: