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

Human Immunodeficiency Virus Type 1 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00838162
• Other study ID #: CR015952
• Secondary ID: TMC310911-TIDP21
• Status: Completed
• Phase: Phase 2
• First received: February 5, 2009
• Last updated: June 3, 2013
• Start date: June 2009
• Est. completion date: February 2011

Study information

• Verified date: June 2013
• Source: Tibotec Pharmaceuticals, Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland: Irish Agriculture and Food Development AuthorityGermany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: February 2011
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus Type 1
• Immunologic Deficiency Syndromes

Intervention

Drug:
• TMC310911 75 mg twice daily
TMC310911 75 mg twice daily orally (by mouth) on Days 1 to 14.
• TMC310911 150 mg twice daily
TMC310911 150 mg twice daily orally (by mouth) on Days 1 to 14
• TMC310911 300 mg twice daily
TMC310911 300 mg twice daily orally (by mouth) on Days 1 to 14
• TMC310911 300 mg once daily
TMC310911 300 mg once daily orally (by mouth) on Days 1 to 14
• Ritonavir 100 mg twice daily
Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14
• Ritonavir 100 mg once daily
Ritonavir 100 mg once daily orally (by mouth) on Days 1 to 14

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tibotec Pharmaceuticals, Ireland

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Mean Changes From Baseline in CD4+ Cell Count		Baseline (Day 1), Day 8, Day 15	No
Secondary	Maximum Plasma Concentration (Cmax) of TMC310911		Day 1 and Day 14	No
Secondary	Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911		Day 1 and Day 14	No
Secondary	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	No
Secondary	Predose Plasma Concentration (C0h) of TMC310911		Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14	No
Secondary	Average Steady-state Plasma Concentration (Css,av) of TMC310911		Day 14	No
Secondary	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	No