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.
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.
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)).
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.
Inclusion Criteria:
Exclusion Criteria: