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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00838162
First received: February 5, 2009
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Human Immunodeficiency Virus Type 1
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
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) [ Time Frame: Baseline (Day 1), Day 8, Day 15 ] [ Designated as safety issue: No ]
    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:
  • Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Day 1), Day 8, Day 15 ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration (Cmax) of TMC310911 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Predose Plasma Concentration (C0h) of TMC310911 [ Time Frame: Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14 ] [ Designated as safety issue: No ]
  • Average Steady-state Plasma Concentration (Css,av) of TMC310911 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  • Fluctuation Index of TMC310911 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    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.


Enrollment: 33
Study Start Date: June 2009
Study Completion Date: February 2011
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: TMC310911 150 mg twice daily
TMC310911 150 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 300/100 mg twice daily
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
Drug: TMC310911 300 mg twice daily
TMC310911 300 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 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

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00838162

Locations
Germany
Berlin, Germany
Frankfurt, Germany
Hamburg, Germany
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
  More Information

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00838162     History of Changes
Other Study ID Numbers: CR015952, TMC310911-TIDP21-C201, 2008-008190-58
Study First Received: February 5, 2009
Results First Received: January 30, 2013
Last Updated: June 3, 2013
Health Authority: Ireland: Irish Agriculture and Food Development Authority
Germany: Ethics Commission

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Human immunodeficiency virus type 1
HIV-1
HIV-1 treatment-naive
TMC310911
Protease inhibitor
Ritonavir
Antiviral Activity
HIV Infections
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Antiviral Agents
Ritonavir
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on July 10, 2014