A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the antiviral activity as measured by the change in viral load from baseline in the 14 days following initiation of treatment with 4 different dose regimens of TMC310911 co-administered with ritonavir.

Detailed Description
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This is an open-label (all people know the identity of the intervention) and randomized (study medication assigned by chance) study in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected participants (participants who had not been treated with a therapeutic HIV vaccine within 1 year prior to enrollment and who had never been treated with an antiretroviral [ARV] medication indicated for the treatment of HIV-infection or ARVs for treatment of hepatitis B infection with anti-HIV activity prior to screening). In this study approximately 32 participants will be enrolled and randomly assigned to receive 4 different dose regimens co-administered with ritonavir (8 participants in each dosing regimen). The trial will consist of a screening period (maximum 6 weeks), a treatment period with TMC310911 (2 weeks), and a follow-up period (4 weeks). Safety evaluation will include assessment of adverse events, clinical laboratory tests, vital sign measurements, physical examinations and electrocardiograms.

Official Title
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A Phase IIa, Open-label, Randomized Trial in Treatment-naive HIV-1-infected Subjects to Determine the Antiviral Activity of 14 Days of Monotherapy With 4 Different Dose Regimens of TMC310911 Coadministered With Ritonavir

Conditions
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Human Immunodeficiency Virus Type 1

Intervention / Treatment
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* Drug: TMC310911 75 mg twice daily
* Drug: TMC310911 150 mg twice daily
* Drug: TMC310911 300 mg twice daily
* Drug: TMC310911 300 mg once daily
* Drug: Ritonavir 100 mg twice daily
* Drug: Ritonavir 100 mg once daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented human immunodeficiency virus type 1 (HIV-1) infection for at least 6 months prior to the screening date Participant who has not been treated with a therapeutic HIV vaccine within 1 year prior to enrolment and has never been treated with an antiretroviral (ARV) medication indicated for the treatment of HIV infection or ARVs for treatment of hepatitis B-infection with anti-HIV activity Participant agrees not to start antiretroviral therapy (ART) before the baseline visit Able to comply with the protocol requirements and have good accessible veins HIV-1 plasma viral load at screening visit of above 5,000 HIV-1 Ribonucleic acid copies/mL CD4+ cell count above 200 cells/mm3 at screening Exclusion Criteria: HIV-2 infected participants and/or participants with any active or chronic hepato-renal disease Life expectancy of less than 6 months Documented acute (primary) HIV-1 infection Pre-existing protease inhibitor (PI) medication resistance Any currently active Acquired Immunodeficiency Syndrome (AIDS) - defining illness Any active clinically significant disease or findings during screening or medical history or physical examination that in the investigator's opinion, would compromise the outcome of the study Any confirmed grade 3 or 4 toxicity according to the Division of AIDS (DAIDS) grading scale at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMC310911/rtv 75/100 mg twice daily<br>TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14 | Drug: TMC310911 75 mg twice daily<br>* TMC310911 75 mg twice daily orally (by mouth) on Days 1 to 14.<br>Drug: Ritonavir 100 mg twice daily<br>* Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14<br>|
| Experimental: TMC310911/rtv 150/100 mg twice daily<br>TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14 | Drug: TMC310911 150 mg twice daily<br>* TMC310911 150 mg twice daily orally (by mouth) on Days 1 to 14<br>Drug: Ritonavir 100 mg twice daily<br>* Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14<br>|
| Experimental: TMC310911/rtv 300/100 mg twice daily<br>TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14 | Drug: TMC310911 300 mg twice daily<br>* TMC310911 300 mg twice daily orally (by mouth) on Days 1 to 14<br>Drug: Ritonavir 100 mg twice daily<br>* Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14<br>|
| Experimental: TMC310911/rtv 300/100 mg once daily<br>TMC310911 300 mg + ritonavir 100 mg once daily on Days 1 to 14 | Drug: TMC310911 300 mg once daily<br>* TMC310911 300 mg once daily orally (by mouth) on Days 1 to 14<br>Drug: Ritonavir 100 mg once daily<br>* Ritonavir 100 mg once daily orally (by mouth) on Days 1 to 14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | The antiviral activity of TMC310911 is measured by the change in viral load from baseline in the 14 days of treatment following initiation of treatment with 4 different dosing regimens of TMC310911 coadministered with ritonavir. | Baseline (Day 1), Day 8, Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Virologic response is a viral load test result below a chosen threshold value (less than 50 copies/mL, less than 400 copies/mL, or at least 1 log drop in viral load) at any timepoint during a 14-day treatment of 4 different dose regimens of TMC310911 coadministered with 100 mg ritonavir. | 14 days | 
| Mean Changes From Baseline in CD4+ Cell Count |  | Baseline (Day 1), Day 8, Day 15 | 
| Maximum Plasma Concentration (Cmax) of TMC310911 |  | Day 1 and Day 14 | 
| Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 |  | Day 1 and Day 14 | 
| Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing |  | Day 1 and Day 14 | 
| Predose Plasma Concentration (C0h) of TMC310911 |  | Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14 | 
| Average Steady-state Plasma Concentration (Css,av) of TMC310911 |  | Day 14 | 
| Fluctuation Index of TMC310911 | Fluctuation index, ie, percentage fluctuation: variation between maximum (Cmax) and minimum (Cmin) plasma concentration at steady-state, calculated as: 100 x ([Cmax-Cmin]/Css,av). Css,av is an average steady-state plasma concentration. | Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, Human immunodeficiency virus type 1, HIV-1 treatment-naive, TMC310911, Protease inhibitor, Ritonavir, Antiviral Activity, HIV Infections, Treatment Naive