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

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

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus Type 1
• Intervention / Treatment: Drug: TMC310911 75 mg twice daily; Drug: Ritonavir 100 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 once daily

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 Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
  • Frankfurt, Germany
  • Hamburg, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TMC310911/rtv 75/100 mg twice daily; TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	Drug: TMC310911 75 mg twice daily; TMC310911 75 mg twice daily orally (by mouth) on Days 1 to 14.; Drug: Ritonavir 100 mg twice daily; Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14
EXPERIMENTAL: TMC310911/rtv 150/100 mg twice daily; TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	Drug: Ritonavir 100 mg twice daily; Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14; Drug: TMC310911 150 mg twice daily; TMC310911 150 mg twice daily orally (by mouth) on Days 1 to 14
EXPERIMENTAL: TMC310911/rtv 300/100 mg twice daily; TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	Drug: Ritonavir 100 mg twice daily; Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14; Drug: TMC310911 300 mg twice daily; TMC310911 300 mg twice daily orally (by mouth) on Days 1 to 14
EXPERIMENTAL: TMC310911/rtv 300/100 mg once daily; TMC310911 300 mg + ritonavir 100 mg once daily on Days 1 to 14	Drug: TMC310911 300 mg once daily; TMC310911 300 mg once daily orally (by mouth) on Days 1 to 14; Drug: Ritonavir 100 mg once daily; Ritonavir 100 mg once daily orally (by mouth) on Days 1 to 14

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tibotec Pharmaceuticals, Ireland

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (ACTUAL): August 1, 2009
• Study Completion (ACTUAL): February 1, 2011

Study Registration Dates

• First Submitted: February 5, 2009
• First Submitted That Met QC Criteria: February 5, 2009
• First Posted (ESTIMATE): February 6, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 12, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: HIV-1; Treatment Naive; Ritonavir; HIV Infections; Protease inhibitor; Antiviral Activity; Human immunodeficiency virus type 1; TMC310911; HIV-1 treatment-naive
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; TMC-310911
• Other Study ID Numbers: CR015952; TMC310911-TIDP21-C201 (OTHER: Tibotec Pharmaceuticals, Ireland); 2008-008190-58 (EUDRACT_NUMBER)