New 48 Week Clinical Trial Data Report on Atazanavir with or without Ritonavir in Treatment-naive Patients

Data presented during the 13^th Conference on Retroviruses and Opportunistic Infections (13^Th CROI) this week provided results on the virologic and immunologic response and safety profile of the once-daily (QD) protease inhibitor REYATAZ (atazanavir), both with or without low-dose ritonavir, as part of combination therapy. Following is the text of an announcement about the trial from Bristol-Myers Squibb:

The clinical trial studied HIV-infected patients who had not received previous antiretroviral treatment (treatment-naive). Results of an intent-to-treat analysis demonstrated that 86% of patients in the REYATAZ/ritonavir arm and 85% of patients in the REYATAZ arm responded to treatment with HIV-RNA levels declining to less than 400 copies per milliliter through 48 weeks, the primary efficacy endpoint.

Results from this study are the first comparative data presented by Bristol-Myers Squibb Company regarding the use of REYATAZ with ritonavir in this patient population.

About The Study

Study BMS089 is a 96-week, randomized, prospective, open-label, multicenter study. Ninety-five patients were randomized to the REYATAZ 300 mg/ritonavir 100 mg treatment group, and 105 patients to the REYATAZ 400 mg treatment group (the approved dose for this patient population), each combined with lamivudine (3TC; Epivir) and the investigational compound stavudine (d4T; Zerit) extended release as a once-daily regimen.

Study entry criteria included patients who were naive to antiretroviral treatment and had plasma HIV-RNA levels of greater than or equal to 2000 copies per milliliter at the time of screening. There were no CD4+ cell count entry restrictions.

Randomization was stratified by HIV-RNA levels greater than or equal to or less than 100,000 copies per milliliter at screening.

The primary efficacy endpoint was the proportion of patients who achieved HIV-RNA levels of less than 400 copies per milliliter through week 48. Secondary efficacy analyses examined the proportion of patients who responded to treatment with HIV-RNA levels of less than 50 copies per milliliter through week 48, CD4+ count changes from baseline through week 48, and safety parameters.

The proportions of patients with HIV-RNA levels of less than 50 copies per milliliter were 75% in the REYATAZ/ritonavir treatment group and 70% in the REYATAZ treatment group. CD4+ cell improvements were observed in both arms (mean changes of +189 and +224 cells per cubic millimeter at week 48 in the REYATAZ/ritonavir and REYATAZ arms, respectively).

Adverse events leading to discontinuations were 8% in the REYATAZ/ritonavir arm and less than 1% in the REYATAZ arm. Serious adverse events occurred in 15% of the patients in the REYATAZ/ritonavir arm and 16% of the patients in the REYATAZ arm.

Grade 2-4 treatment-related adverse events were reported in 43% of patients in the REYATAZ/ritonavir arm and 34% of the patients in the REYATAZ arm with the following being reported in greater than or equal to 3% of patients in either of the arms, respectively: hyperbilirubinemia reported as a clinical adverse event (13% vs. 5%), headache (2% vs. 4%), rash (2% vs. 4%), and jaundice (3% vs. less than 1%).

Selected Grade 3-4 laboratory abnormalities occurred in the REYATAZ/ritonavir and REYATAZ arms, respectively, as follows: total bilirubin elevation (59% vs. 20%), alanine aminotransaminase elevation (6% vs. 3%), aspartate aminotransferase elevation (3% in both arms), total cholesterol elevation (1% vs. less than 1%), triglyceride elevation (2% vs. less than 1%), and hyperglycemia (1% vs. less than 1%).

At week 48, mean changes in lipid parameters from baseline for patients in the REYATAZ/ritonavir arm versus the REYATAZ arm were as follows, respectively: total cholesterol (15% vs. 6%), fasting LDL cholesterol (23% vs. 16%), HDL cholesterol (30% vs. 29%), and fasting triglycerides (26% vs. -3%).

The primary analysis was based on the data available 48 weeks after the last patient was randomized. A final analysis will be conducted 96 weeks after the last patient is randomized to assess long-term safety and virologic response.

02/10/06

Source
Bristol-Myers Squibb. New 48 Week Clinical Trial Data Reported Comparing Reyataz (Atazanavir sulfate), with or without ritonavir, in treatment-naïve Patients. Press Release. February 9, 2006.