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

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.

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: TMC114/rtv; Drug: TMC114/rtv; Drug: TMC114/rtv; Drug: TMC114/rtv

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.

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
  • California
    • Beverly Hills, California, United States
    • Long Beach, California, United States
    • Los Angeles, California, United States
    • Oakland, California, United States
    • San Diego, California, United States
    • San Francisco, California, United States
    • West Hollywood, California, United States
  • Colorado
    • Denver, Colorado, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Altamonte Springs, Florida, United States
    • Fort Lauderdale, Florida, United States
    • Ft Lauderdale, Florida, United States
    • Miami, Florida, United States
    • Miami Beach, Florida, United States
    • Tampa, Florida, United States
    • Vero Beach, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Macon, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Springfield, Massachusetts, United States
  • New Jersey
    • Camden, New Jersey, United States
  • New York
    • Albany, New York, United States
    • New York, New York, United States
  • North Carolina
    • Huntersville, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
  • South Carolina
    • Columbia, South Carolina, United States
  • Texas
    • Dallas, Texas, United States
    • Galveston, Texas, United States
    • Houston, Texas, United States
  • Virginia
    • Hampton, Virginia, United States
  • Washington
    • Seattle, Washington, United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; TMC114/rtv 400mg TMC114/100mg rtv once daily	Drug: TMC114/rtv; 800mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv both twice daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 600mg TMC114/100mg rtv twice daily
No Intervention: 005; Control Group Control Group, no intervention
Experimental: 004; TMC114/rtv 600mg TMC114/100mg rtv twice daily	Drug: TMC114/rtv; 800mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv both twice daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 600mg TMC114/100mg rtv twice daily
Experimental: 003; TMC114/rtv 400mg TMC114/100mg rtv both twice daily	Drug: TMC114/rtv; 800mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv both twice daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 600mg TMC114/100mg rtv twice daily
Experimental: 002; TMC114/rtv 800mg TMC114/100mg rtv once daily	Drug: TMC114/rtv; 800mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv both twice daily; Drug: TMC114/rtv; 400mg TMC114/100mg rtv once daily; Drug: TMC114/rtv; 600mg TMC114/100mg rtv twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	144 weeks

Collaborators and Investigators

• Sponsor: Tibotec Pharmaceuticals, Ireland

Publications and helpful links

General Publications

• Clotet B, Bellos N, Molina JM, Cooper D, Goffard JC, Lazzarin A, Wohrmann 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. doi: 10.1016/S0140-6736(07)60497-8. Erratum In: Lancet. 2008 Jan 12;371(9607):116.
• De Meyer SM, Spinosa-Guzman S, Vangeneugden TJ, de Bethune 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: October 10, 2003
• First Submitted That Met QC Criteria: October 14, 2003
• First Posted (Estimate): October 15, 2003

Study Record Updates

• Last Update Posted (Estimate): September 20, 2016
• Last Update Submitted That Met QC Criteria: September 19, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: HIV; Tolerability; Ritonavir; TMC114; Safety and efficacy; TMC114-C211
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Darunavir
• Other Study ID Numbers: CR006778; TMC114-C202