TMC114-C202: A Study of Safety, Efficacy, and Tolerability of TMC114 and Low Dose Ritonavir in HIV-1 Infected Patients - Full Text View

Purpose

The purpose of this study is to determine the effectiveness, safety, and tolerability (how well the body stands the drug) of an investigational protease inhibitor (PI) called TMC114 given with low dose ritonavir.

Condition	Intervention	Phase
HIV Infections	Drug: TMC114/rtv Other: Control Group	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose Response of TMC114/RTV in 3-class-experienced HIV-1 Infected Patients, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:

To evaluate the dose-response relationship of antiviral activity of the TMC114/RTV dose regimens at 24 Wks in order to determine the optimal dose. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate safety and tolerability over 24 to 144Wks; The durability of the antiviral activity; The effect of functional monotherapy with TMC114 over 2 weeks in different doses; and The dose-response by comparing the different TMC114/RTV dosages. [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]


Enrollment:	330
Study Start Date:	December 2004
Study Completion Date:	November 2007
Primary Completion Date:	February 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 001 TMC114/rtv 400mg TMC114/100mg rtv once daily	Drug: TMC114/rtv 400mg TMC114/100mg rtv once daily
No Intervention: 005 Control Group Control Group, no intervention	Other: Control Group Control Group, no intervention
Experimental: 004 TMC114/rtv 600mg TMC114/100mg rtv twice daily	Drug: TMC114/rtv 600mg TMC114/100mg rtv twice daily
Experimental: 003 TMC114/rtv 400mg TMC114/100mg rtv both twice daily	Drug: TMC114/rtv 400mg TMC114/100mg rtv both twice daily
Experimental: 002 TMC114/rtv 800mg TMC114/100mg rtv once daily	Drug: TMC114/rtv 800mg TMC114/100mg rtv once daily

Detailed Description:

A phase II randomized, controlled, partially blinded, trial to investigate dose response of TMC114/RTV in HIV-1 infected patients who have previously received all three licensed classes of HIV antiviral drugs (known as nucleoside reverse transcriptase inhibitors (NRTI), nonnucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI)), and who are on a stable PI-containing regimen not including an NNRTI may be eligible to participate. Four doses of TMC-114/ritonavir will be studied. 300 patients in the United States and Puerto Rico will participate. The duration of the study is 96 weeks. Randomize to one of 4 treatment groups (TMC114/RTV: 400/100 mg qd; 800/100mg qd; 400/100mg bid; 600/100 bid) or control arm for 24 to 48 wks. Optimal dose (TMC114/RTV 600/100mg bid) open label portion of the study. The trial was extended to include 144Wks of treatment.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female, age 18 years or older
Documented HIV-1 infection
Stable PI regimen for at least 8 weeks prior to screening
Plasma viral load at screening above 1000 HIV-1 RNA copies/ml
Prior use of more than 1 NRTI for at least 3 months
Prior use of one or more NNRTIs as part of a failing regimen
At least 1 primary PI mutation as defined by the IAS guidelines
Treatment with at least 1 PI for a total of at least 3 months
Patient has given informed consent

Exclusion Criteria:

Presence of any currently active AIDS defining illness except stable cutaneous Kaposi's Sarcoma and Wasting syndrome due to HIV infection
Current or past history of alcohol and/or drug abuse which, in the investigator's opinion, would compromise the subject's safety or compliance to the study protocol procedures
NNRTI as part of therapy at screening
Patients on a treatment interruption at screening
Patients for whom an investigational antiretroviral therapy is part of the regimen at screening or the use of any non-antiretroviral investigational agents 90 days prior to screening
Hepatitis A, B, or C.

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: NCT00071097

Sponsors and Collaborators

Tibotec Pharmaceuticals, Ireland

Investigators


Study Director:	Tibotec Pharmaceuticals Clinical Trial	Tibotec Pharmaceutical Limited

More Information

Publications:

Clotet B, Bellos N, Molina JM, Cooper D, Goffard JC, Lazzarin A, Wöhrmann A, Katlama C, Wilkin T, Haubrich R, Cohen C, Farthing C, Jayaweera D, Markowitz M, Ruane P, Spinosa-Guzman S, Lefebvre E; POWER 1 and 2 study groups. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet. 2007 Apr 7;369(9568):1169-78. Erratum in: Lancet. 2008 Jan 12;371(9607):116.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

De Meyer SM, Spinosa-Guzman S, Vangeneugden TJ, de Béthune MP, Miralles GD. Efficacy of once-daily darunavir/ritonavir 800/100 mg in HIV-infected, treatment-experienced patients with no baseline resistance-associated mutations to darunavir. J Acquir Immune Defic Syndr. 2008 Oct 1;49(2):179-82. doi: 10.1097/QAI.0b013e318183a959.


Responsible Party:	Compound Development Team Leader TMC114, Tibotec Pharmaceutical Limited
ClinicalTrials.gov Identifier:	NCT00071097 History of Changes
Obsolete Identifiers:	NCT00980928
Other Study ID Numbers:	CR006778, TMC114-C202
Study First Received:	October 10, 2003
Last Updated:	June 2, 2011
Health Authority:	United States: Food and Drug Administration Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:


HIV TMC114 Ritonavir	Tolerability Safety and efficacy TMC114-C211

Additional relevant MeSH terms:


Darunavir Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors	HIV Protease Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protease Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015