TMC114-C202: A Study of Safety, Efficacy, and Tolerability of TMC114 and Low Dose Ritonavir in HIV-1 Infected Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effectiveness, safety, and tolerability (how well the body stands the drug) of an investigational protease inhibitor (PI) called TMC114 given with low dose ritonavir.

Detailed Description
-----------------
A phase II randomized, controlled, partially blinded, trial to investigate dose response of TMC114/RTV in HIV-1 infected patients who have previously received all three licensed classes of HIV antiviral drugs (known as nucleoside reverse transcriptase inhibitors (NRTI), nonnucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI)), and who are on a stable PI-containing regimen not including an NNRTI may be eligible to participate. Four doses of TMC-114/ritonavir will be studied. 300 patients in the United States and Puerto Rico will participate. The duration of the study is 96 weeks. Randomize to one of 4 treatment groups (TMC114/RTV: 400/100 mg qd; 800/100mg qd; 400/100mg bid; 600/100 bid) or control arm for 24 to 48 wks. Optimal dose (TMC114/RTV 600/100mg bid) open label portion of the study. The trial was extended to include 144Wks of treatment.

Official Title
-----------------
A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose Response of TMC114/RTV in 3-class-experienced HIV-1 Infected Patients, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: TMC114/rtv
* Drug: TMC114/rtv
* Drug: TMC114/rtv
* Drug: TMC114/rtv


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, age 18 years or older Documented HIV-1 infection Stable PI regimen for at least 8 weeks prior to screening Plasma viral load at screening above 1000 HIV-1 RNA copies/ml Prior use of more than 1 NRTI for at least 3 months Prior use of one or more NNRTIs as part of a failing regimen At least 1 primary PI mutation as defined by the IAS guidelines Treatment with at least 1 PI for a total of at least 3 months Patient has given informed consent Exclusion Criteria: Presence of any currently active AIDS defining illness except stable cutaneous Kaposi's Sarcoma and Wasting syndrome due to HIV infection Current or past history of alcohol and/or drug abuse which, in the investigator's opinion, would compromise the subject's safety or compliance to the study protocol procedures NNRTI as part of therapy at screening Patients on a treatment interruption at screening Patients for whom an investigational antiretroviral therapy is part of the regimen at screening or the use of any non-antiretroviral investigational agents 90 days prior to screening Hepatitis A, B, or C.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>TMC114/rtv 400mg TMC114/100mg rtv once daily | Drug: TMC114/rtv<br>* 400mg TMC114/100mg rtv once daily<br>|
| No Intervention: 005<br>Control Group Control Group, no intervention | |
| Experimental: 004<br>TMC114/rtv 600mg TMC114/100mg rtv twice daily | Drug: TMC114/rtv<br>* 600mg TMC114/100mg rtv twice daily<br>|
| Experimental: 003<br>TMC114/rtv 400mg TMC114/100mg rtv both twice daily | Drug: TMC114/rtv<br>* 400mg TMC114/100mg rtv both twice daily<br>|
| Experimental: 002<br>TMC114/rtv 800mg TMC114/100mg rtv once daily | Drug: TMC114/rtv<br>* 800mg TMC114/100mg rtv once daily<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the dose-response relationship of antiviral activity of the TMC114/RTV dose regimens at 24 Wks in order to determine the optimal dose. |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability over 24 to 144Wks; The durability of the antiviral activity; The effect of functional monotherapy with TMC114 over 2 weeks in different doses; and The dose-response by comparing the different TMC114/RTV dosages. |  | 144 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, TMC114, Ritonavir, Tolerability, Safety and efficacy, TMC114-C211