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

Phase 2

Completed

• Conditions: Human Immunodeficiency Virus Type 1
• Interventions: 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

• Registration Number: NCT00838162
• Lead Sponsor: Tibotec Pharmaceuticals, Ireland

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2009-02-05
• Study First Submitted QC: 2009-02-05
• Study First Posted: 2009-02-06
• Study Start: 2009-06
• Primary Completion: 2009-08
• Study Completion: 2011-02
• Disposition First Submitted: 2011-07-01
• Disposition First Submitted QC: 2011-07-01
• Disposition First Posted: 2011-07-14
• Results First Submitted: 2013-01-30
• Results First Submitted QC: 2013-01-30
• Results First Posted: 2013-03-07
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-03
• Last Update Posted: 2013-06-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TMC310911/rtv 75/100 mg twice daily	TMC310911 75 mg twice daily	TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911/rtv 75/100 mg twice daily	Ritonavir 100 mg twice daily	TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911/rtv 150/100 mg twice daily	TMC310911 150 mg twice daily	TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911/rtv 150/100 mg twice daily	Ritonavir 100 mg twice daily	TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911/rtv 300/100 mg twice daily	TMC310911 300 mg twice daily	TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911/rtv 300/100 mg twice daily	Ritonavir 100 mg twice daily	TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911/rtv 300/100 mg once daily	TMC310911 300 mg once daily	TMC310911 300 mg + ritonavir 100 mg once daily on Days 1 to 14
TMC310911/rtv 300/100 mg once daily	Ritonavir 100 mg once daily	TMC310911 300 mg + ritonavir 100 mg once daily on Days 1 to 14

Primary Outcome Measures

Name	Time	Method
Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA)	Baseline (Day 1), Day 8, Day 15	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period	14 days	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.
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	Day 14	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.