GRACE: A Study to Compare the Effectiveness, Safety and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race When Administered With Other Antiretroviral Medications in Human Immunodeficiency Virus (HIV) Positive Women and Men.

This study has been completed.
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
Tibotec, Inc
ClinicalTrials.gov Identifier:
NCT00381303
First received: September 26, 2006
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to evaluate any differences in the effectiveness, safety, and tolerability of PREZISTA (darunavir; DRV) 600 mg, administered with ritonavir (RTV) 100 mg twice a day on virologic response (defined as a viral load (VL) of < 50 copies/mL) over a 48-week treatment period in HIV-positive women and men. Additional antiretroviral (ARV) agents will also be administered and will be chosen by the Investigator based on resistance testing and prior treatment history (referred to as the Optimized Background Regimen (OBR)).


Condition Intervention Phase
HIV
Infectious
Drug: darunavir
Drug: ritonavir
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: GRACE: An Open-label, Multicenter Trial to Compare the Efficacy, Safety, and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race, When Administered in Combination With an Individually Optimized Background Regimen Over a 48-week Treatment Period.

Resource links provided by NLM:


Further study details as provided by Tibotec, Inc:

Primary Outcome Measures:
  • Number of Viral Load (VL) < 50 HIV-1 RNA Copies/mL (Time to Loss of Virologic Response[TLOVR]) Subjects by Sex [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    TLOVR - responders/non-responders per FDA TLOVR response algorithm. A subject was considered a responder at that time point and that subsequent. A subject was considered a non-responder at a time point in the following situations: discontinued treatment at that time point, a rebound value at that time point and that subsequent or at that time point and that followed by treatment discontinuation, intermittent missing values were considered a response if the immediately preceding and following visits were a response, rebound at earlier time point, or any new, unplanned ARV except in tolerability

  • Number of TLOVR Non-virologic Failure (VF) Censored - VL < 50 HIV-1 RNA Subjects by Sex [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    TLOVR non-virologic failure (VF) censored. This imputation method differs from the TLOVR algorithm, because subjects that dropped out for reasons other than virologic failure were censored from the time of discontinuation onwards.


Secondary Outcome Measures:
  • Number of VL < 50 HIV-1 RNA Copies/mL (TLOVR) Subjects by Race [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Intention to Treat population (ITT)

  • Number of Etravirine-TMC125 (ETR) Subgroup- VL < 50 HIV-1 RNA Copies/mL (TLOVR) Subjects [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR)

  • Descriptive Statistics of [TLOVR Non-virologic Failure (VF) Censored] - VL < 50 HIV-1 RNA by Race [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    TLOVR non-virologic failure (VF) censored. This imputation method differs from the TLOVR algorithm, because subjects that dropped out for reasons other than virologic failure were censored from the time of discontinuation onwards.

  • Descriptive Statistics of ETR Subgroup [TLOVR Non-virologic Failure (VF) Censored] - VL < 50 HIV-1 RNA [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR)

    TLOVR non-virologic failure(VF) censored. This imputation method differs from the TLOVR algorithm, because subjects that dropped out for reasons other than virologic failure were censored from the time of discontinuation onwards.


  • Descriptive Statistics of Change From Baseline in CD4+ Cell Count Using Observed Values [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Observed obsevations have no imputation methods applied.

  • Descriptive Statistics of ETR Subgroup - Change From Baseline in CD4+ Cell Using Observed Values [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR)

  • Descriptive Statistics of Change From Baseline in CD4+ Cell Count Using the Imputation Method of Last Observation Carried Forward (LOCF) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Last Observation Carried Forward (LOCF) imputation method applied.

  • Descriptive Statistics of ETR Subgroup - Change From Baseline in CD4+ Cell Count Using the Imputation Method of LOCF [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR). The Last Observation Carried Forward (LOCF) imputation method was applied.


Enrollment: 429
Study Start Date: November 2006
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
darunavir 600mg bid for 48 wks,ritonavir 100mg bid for 48 wks
Drug: darunavir
600mg bid for 48 wks
Drug: ritonavir
100mg bid for 48 wks

Detailed Description:

This is a multi-center, open-label (doctors and patients know which drug is being administered), Phase IIIb clinical trial to evaluate differences in effectiveness, safety, and tolerability of darunavir/ritonavir by sex and/or race over a 48-week treatment period. This study will be conducted in HIV positive women and men who have been treated previously with antiretroviral therapy. This study will enroll 70% women and will be conducted in the U.S., Puerto Rico, Mexico and Canada in approximately 420 patients who will receive darunavir 600 mg and ritonavir 100 mg twice daily. The primary objective of this study is to determine the percentage of patients who achieve virologic response, defined as a viral load (VL) of <50 copies/mL at week 48. Secondary study objectives include comparisons of endpoints between women and men as well as race across multiple parameters including but not limited to change in CD4 count from baseline to week 48, time to loss of virologic response (TLOVR), changes in metabolic parameters (blood chemistry), etc.

Within 4 weeks after the Screening Visit (initial visit with investigator to determine eligibility), the Investigator should have received all data required to determine the patient's eligibility and will construct the individual Optimized Background Regimen (OBR) that will be used during the treatment period in combination with darunavir/ritonavir for those patients enrolled in the study. The OBR will consist of additional antiretroviral (ARV) agents that will also be administered during the study chosen by the Investigator and based on resistance testing and prior treatment history. The study Sponsor will provide the following ARV agents, that may be used as options for the OBR: TMC 125 (investigational non-nucleoside reverse transcriptase inhibitor; NNRTI); Truvada (tenofovir/emtricitabine); Viread (tenofovir); Emtriva (emtricitabine); Zidovudine. Other NRTIs (nucleoside reverse transcriptase inhibitors) or NNRTIs may be used at the discretion of the Investigator, but will not be provided by the Sponsor. The Baseline Visit (Day 1) will be followed by a 48-week treatment period during which patients will be evaluated at Weeks 4, 8, 12, 16, 24, 36, 48 and at a final Follow-Up Visit during Week 52. (total of 10 visits from Screening to final visit). At a number of visits throughout the study, blood samples will be obtained to assess defined laboratory values, safety parameters and to determine concentrations of study drugs darunavir, TMC125 (if applicable) and ritonavir). Patients will be assessed for change in CD4 count and HIV-RNA throughout the study. At each visit, vital signs will be assessed and patients will be asked about any untoward medical occurrences and these will be recorded as adverse events (AEs) and/or HIV-related events. Detailed definitions and reporting procedures for AEs will be provided as part of the protocol. Study patients will receive PREZISTA (darunavir) 600 mg boosted with 100 mg of ritonavir orally (by mouth) twice a day in combination with other antiretroviral drugs for 48 weeks.

  Eligibility

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

Inclusion Criteria:

  • Documented HIV infection
  • Plasma HIV-RNA >= 1000 copies/mL
  • Must be able to comply with protocol requirements

Exclusion Criteria:

  • No prior use of PREZISTA (darunavir), TMC125, enfuvirtide, or tipranavir
  • No currently active AIDS defining illness, Category C conditions according to the Center for Disease Control [CDC] Classification System for HIV Infection (1993) with the following exceptions, which must be discussed with the Sponsor prior to enrollment: stable cutaneous Kaposi's Sarcoma, Wasting syndrome due to HIV infection
  • Not currently using an investigational drug
  • Not pregnant or breastfeeding
  • No Grade 3 or 4 laboratory abnormality as defined by DAIDS (Division of AIDS, National Institute of Allergy and Infectious Diseases).
  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: NCT00381303

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States
United States, Arizona
Phoenix, Arizona, United States
United States, California
Los Angeles, California, United States
Sacramento, California, United States
Torrance, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Fort Lauderdale, Florida, United States
Jacksonville, Florida, United States
Miami, Florida, United States
North Palm Beach, Florida, United States
Orlando, Florida, United States
Pensacola, Florida, United States
Port St Lucie, Florida, United States
West Palm Beach, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
Savannah, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Kansas
Kansas City, Kansas, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
Springfield, Massachusetts, United States
United States, Michigan
Detroit, Michigan, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, New Jersey
Neptune, New Jersey, United States
Newark, New Jersey, United States
United States, New York
Bronx, New York, United States
New York, New York, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
Durham, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Austin, Texas, United States
Dallas, Texas, United States
Harlingen, Texas, United States
Houston, Texas, United States
Longview, Texas, United States
San Antonio, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Virginia
Charlottesville, Virginia, United States
Canada, Ontario
Hamilton, Ontario, Canada
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Puerto Rico
Ponce, Puerto Rico
Rio Piedras, Puerto Rico
Sponsors and Collaborators
Tibotec, Inc
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
Study Director: Tibotec, Inc. Clinical Trial Tibotec, Inc
  More Information

No publications provided by Tibotec, Inc

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tibotec, Inc
ClinicalTrials.gov Identifier: NCT00381303     History of Changes
Other Study ID Numbers: CR011869, TMC114HIV3004
Study First Received: September 26, 2006
Results First Received: November 24, 2009
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tibotec, Inc:
HIV
AIDS
Immunodeficiency Virus, Human
Females
Women
PREZISTA
darunavir
TMC114
Protease Inhibitor

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
HIV Seropositivity
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Darunavir
Ritonavir
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 October 22, 2014