Clinical trial NCT00838162: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Human Immunodeficiency Virus Type 1
Keywords: Human immunodeficiency virus type 1
HIV-1
HIV-1 treatment-naive
TMC310911
Protease inhibitor
Ritonavir
Antiviral Activity
HIV Infections
Treatment Naive
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2009-02-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA)
timeFrame: Baseline (Day 1), Day 8, Day 15
Secondary outcomes:
measure: Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period
timeFrame: 14 days
measure: Mean Changes From Baseline in CD4+ Cell Count
timeFrame: Baseline (Day 1), Day 8, Day 15
measure: Maximum Plasma Concentration (Cmax) of TMC310911
timeFrame: Day 1 and Day 14
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911
timeFrame: Day 1 and Day 14
measure: Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing
timeFrame: Day 1 and Day 14
measure: Predose Plasma Concentration (C0h) of TMC310911
timeFrame: Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14
measure: Average Steady-state Plasma Concentration (Css,av) of TMC310911
timeFrame: Day 14
measure: Fluctuation Index of TMC310911
timeFrame: Day 14
Other outcomes:
Locations:
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland Clinical Trial
role: STUDY_DIRECTOR
References: