Estimate The Effect Of Lersivirine On The Pharmacokinetics Of S- And R-Methadone

Study Overview
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Brief Summary
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The objective of this study is to estimate the effect of lersivirine on the pharmacokinetics of R-methadone and S-methadone and to investigate the safety and tolerability of lersivirine when co-administered with methadone. Symptoms of methadone withdrawal will also be assessed.

Official Title
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Open Label, Single-Sequence Study To Estimate The Effect Of Lersivirine (UK-453,061) On S- And R-Methadone In Subjects Receiving Chronic Methadone Treatment

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Methadone
* Drug: Lersivirine + Methadone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history except drug abuse), full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests). Body Mass Index (BMI) of 17.5 to 35.5 kg/m2; and a total body weight >50 kg (110 lbs). Receiving stable methadone maintenance treatment for at least 3 months (dose range 50-150 mg QD). Exclusion Criteria: Subjects on therapy for Hepatitis B and/or Hepatitis C; Evidence of impaired liver function (ie, AST and/or ALT greater than 3 times the upper limit of normal, total bilirubin >1.5 times the upper limit of normal, albumin <3.5 g/dL). 12-lead ECG demonstrating QTc >450 msec for males and QTc >470 msec for females or any other clinically significant abnormalities at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methadone<br>Dose of methadone must not change from 1 week prior to study start and through the duration of the study. | Drug: Methadone<br>* Methadone 50 - 150 mg QD (Day 1)<br>|
| Experimental: Lersivirine + Methadone<br> | Drug: Lersivirine + Methadone<br>* Lersivirine 1000 mg QD + Methadone 50 - 150 mg QD (Days 2-11)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R-methadone and S-methadone plasma pharmacokinetic parameters: AUC24, Cmax, Tmax, and C24h on Days 1 and 11 |  | Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toleration assessed by spontaneous reporting of adverse events, vital signs, 12-lead ECG and laboratory safety assessments |  | Day 12 | 
| Symptoms of methadone withdrawal as assessed by the Short Opiate Withdrawal Scale (SOWS), Desires for Drug Questionnaire (DDQ) and Pupillary Diameter measurement performed on Days 0 -12. |  | Day 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug interaction, pharmacokinetics, lersivirine, methadone