Interaction Study to Assess the Pharmacokinetic Interaction of Oral Administration of Rifapentine on ATRIPLA™ in HIV Patients

Study Overview
=================
Brief Summary
-----------------
Primary Objective: - To evaluate the effect of single and repeated administration of rifapentine given as daily or weekly regimen on steady-state pharmacokinetic parameters of efavirenz, emtricitabine and tenofovir given as a fixed dose combination (ATRIPLA™ ). Secondary Objective: - To evaluate the safety and tolerability of concomitant administration of rifapentine and ATRIPLA™ given to HIV+ patients

Detailed Description
-----------------
Screening to admission: up to 21 days Admission to the end of the follow-up: up to 41 days Period 1: Treatment period of 15 days with ATRIPLA™ (background therapy). Patients should receive the same regimen and dose of ATRIPLA™ during the all study screening and period 1. Period 2: Treatment over a period of 21 days in co-administration with rifapentine. Follow up: 3 to 5 days after the last rifapentine administration.

Official Title
-----------------
An Open-label, Non-randomized, Single Sequence, Two Periods, Four-treatment, Three Parallel Groups Pharmacokinetic Interaction Study of Repeated Oral Doses (Daily or Weekly Regimen) of Rifapentine on ATRIPLA™ (Fixed Dose Combination of Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate) Given to HIV+ Patients

Conditions
-----------------
Tuberculosis

Intervention / Treatment
-----------------
* Drug: rifapentine (M000473)
* Drug: EFZ EMT TDF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : - HIV+ male and female patients receiving ATRIPLA™ aged 18 to 55 years old with a CD4 count cells of at least 350 Exclusion criteria: Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, haematological (patients with porphyria), neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynaecologic (if female), or infectious disease, or signs of acute illness other than HIV disease. Active or latent tuberculosis infection The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort 1<br>Period 1 (15 days) : ATRIPLA™ Period 2 (21 days) : ATRIPLA™ + oral rifapentine (regimen 1). | Drug: rifapentine (M000473)<br>* Pharmaceutical form:tablet Route of administration: oral<br>Drug: EFZ EMT TDF<br>* Pharmaceutical form:tablet Route of administration: oral<br>* Other names: ATRIPLA™;|
| Experimental: cohort 2<br>Period 1 (15 days) : ATRIPLA™ Period 2 (21 days) : ATRIPLA™ + oral rifapentine (regimen 2). | Drug: rifapentine (M000473)<br>* Pharmaceutical form:tablet Route of administration: oral<br>Drug: EFZ EMT TDF<br>* Pharmaceutical form:tablet Route of administration: oral<br>* Other names: ATRIPLA™;|
| Experimental: cohort 3 (optional)<br>Period 1 (15 days) : ATRIPLA™ Period 2 (21 days) : ATRIPLA™ + oral rifapentine (regimen 3). | Drug: rifapentine (M000473)<br>* Pharmaceutical form:tablet Route of administration: oral<br>Drug: EFZ EMT TDF<br>* Pharmaceutical form:tablet Route of administration: oral<br>* Other names: ATRIPLA™;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine PK parameters Cmax, Cmin and AUC0-24 for efavirenz (EFZ), emtricitabine (EMT) and tenofovir (TDF) |  | Day-2, Day 1 and Day 21 for cohorts 1 and 3, and on Day -2 ,Day 1 and Day 16 for cohort 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine PK parameters t1/2z, tmax for efavirenz (EFZ), emtricitabine (EMT) and tenofovir (TDF) |  | Day-2, Day 1 and Day 21 for cohorts 1 and 3, and on Day -2, Day 1 and Day 16 for cohort 2 | 
| To determine PK parameters tlag, CL/F for efavirenz (EFZ), emtricitabine (EMT) and tenofovir (TDF) |  | Day-2, Day 1 and Day 21 for cohorts 1 and 3, and on Day -2, Day 1 and Day 16 for cohort 2 | 
| To determine PK parameter for AUC0-10 for efavirenz (EFZ), emtricitabine (EMT) and tenofovir (TDF) |  | Day -2 and Day 1 for cohorts 1 and 3 | 
| To determine PK parameters Ctrough for rifapentine and 25-desacetyl- rifapentine (25-DR) |  | Cohort 2: Day 1, 8, and 15 | 
| To determine PK parameters C8h for rifapentine and 25-desacetyl- rifapentine (25-DR) |  | Cohort 2: Day 1, 8, and 15 |