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 - Full Text View

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 Intervention Model: Parallel Assignment Masking: None (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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir

U.S. FDA Resources

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 ]
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 ]
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 ]
Maximum Plasma Concentration (Cmax) of TMC310911 [ Time Frame: Day 1 and Day 14 ]
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 [ Time Frame: 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 [ Time Frame: Day 1 and Day 14 ]
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 ]
Average Steady-state Plasma Concentration (Css,av) of TMC310911 [ Time Frame: Day 14 ]
Fluctuation Index of TMC310911 [ Time Frame: 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.


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

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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


Responsible Party:	Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:	NCT00838162 History of Changes
Other Study ID Numbers:	CR015952 TMC310911-TIDP21-C201 ( Other Identifier: Tibotec Pharmaceuticals, Ireland ) 2008-008190-58 ( EudraCT Number )
First Submitted:	February 5, 2009
First Posted:	February 6, 2009
Results First Submitted:	January 30, 2013
Results First Posted:	March 7, 2013
Last Update Posted:	June 12, 2013
Last Verified:	June 2013

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:


Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome HIV Infections Immune System Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases	Ritonavir Antiviral Agents HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors