Study to Estimate the Pharmacokinetics, Bioavailability and Effect of Food on Single Dose Modified-release Lersivirine 500 mg in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to estimate the pharmacokinetics (PK) of 3 different modified-release formulations of lersivirine and compare it to the PK of the immediate-release tablet. The effect of food on the PK of one of the modified-release tablets will also be assess along with the safety and tolerability of each treatment.

Official Title
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Open-Label, Randomized, Crossover Study to Estimate the Pharmacokinetics, Bioavailability and Effect of Food on Single Dose Modified-Release Lersivirine (UK-453,061) 500 mg in Healthy Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Lersivirine Immediate-Release (fasted)
* Drug: Lersivirine Modified-Release #1 (fasted)
* Drug: Lersivirine Modified-Release #2 (fasted)
* Drug: Lersivirine Modified-Release #3 (fasted)
* Drug: Lersivirine Modified-Release (fed)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening; Treatment with an investigational drug within 60 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication; Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lersivirine<br> | Drug: Lersivirine Immediate-Release (fasted)<br>* Single 500 mg dose of Lersivirine Immediate-Release Tablets (2 x 250 mg)<br>Drug: Lersivirine Modified-Release #1 (fasted)<br>* Single 500 mg dose of Lersivirine Modified-Release Tablet #1<br>Drug: Lersivirine Modified-Release #2 (fasted)<br>* Single 500 mg dose of Lersivirine Modified-Release Tablet #2<br>Drug: Lersivirine Modified-Release #3 (fasted)<br>* Single 500 mg dose of Lersivirine Modified-Release Tablet #3<br>Drug: Lersivirine Modified-Release (fed)<br>* Single 500 mg dose of Lersivirine Modified-Release Tablet dosed with food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lersivirine Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] |  | T = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours post dose | 
| Lersivirine Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |  | T = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours post dose | 
| Lersivirine Maximum Observed Plasma Concentration (Cmax) |  | T = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lersivirine Plasma Decay Half-Life (t1/2) |  | T = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours post dose | 
| Lersivirine Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | T = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours post dose | 
| Lersivirine Observed Plasma Concentration at time 24hr (C24) |  | T = 24 hours post dose | 
| Lersivirine Last Observed Plasma Concentration (Clast) |  | T = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioavailability, Pharmacokinetics, Lersivirine, Modified-release