On January 7, 2010, FDA approved an updated Atripla label including new efficacy, safety and resistance data in treatment experienced patients from a trial (Study 073: A Phase IV, Open-Label, Randomized, Multicenter Study Evaluating Efficacy and Tolerability of single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir DF Compared to Unmodified HAART in HIV-1 Infected Subjects Who Have Achieved Virological Suppression on their HAART Regimen) in which HIV-1 infected adults on a stable antiretroviral regimen were either switched to Atripla or remained on their background regimen to compare the effectiveness (efficacy, safety, and tolerability)of Atripla to that of subjects continuing unmodified HAART as measured by the proportion of subjects who maintain HIV-1 RNA <200 copies/mL on their original assigned regimen at Week 48 based on the time-to-loss of virologic response (TLOVR) analysis.
The following additions were made to the package insert with respect to Study 073.
6.1 Adverse Reactions from Clinical Trials Experience
In Study 073, subjects with stable, virologic suppression on antiretroviral therapy and no history of virologic failure were randomized to receive ATRIPLA or to stay on their baseline regimen. The adverse reactions observed in Study 073 were generally consistent with those seen in Study 934* and those seen with the individual components of ATRIPLA when each was administered in combination with other antiretroviral agents
6.2 Laboratory Abnormalities
Laboratory abnormalities observed in Study 073 were generally consistent with those in Study 934
14 CLINICAL STUDIES
Clinical Study 073 provides clinical experience in subjects with stable, virologic suppression and no history of virologic failure who switched from their current regimen to ATRIPLA.
Study 073: Study 073 was a 48-week open-label, randomized clinical trial in subjects with stable, virologic suppression on combination antiretroviral therapy consisting of at least two nucleoside reverse transcriptase inhibitors (NRTIs) administered in combination with a protease inhibitor (with or without ritonavir) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). To be enrolled, subjects were to have HIV-1 RNA <200 copies/mL for at least 12 weeks on their current regimen prior to study entry with no known HIV-1 substitutions conferring resistance to the components of ATRIPLA and no history of virologic failure.
The study compared the efficacy of switching to ATRIPLA or staying on the baseline antiretroviral regimen (SBR). Subjects were randomized in a 2:1 ratio to switch to ATRIPLA (N=203) or stay on SBR (N=97). Subjects had a mean age of 43 years (range 22 to 73 years), 88% were male, 68% were white, 29% were black or African-American, and 3% were of other races. At baseline, median CD4+ cell count was 516 cells/mm3 and 96% had HIV-1 RNA <50 copies/mL. The median time since onset of antiretroviral therapy was 3 years and 88% of subjects were receiving their first antiretroviral regimen at study enrollment.
At Week 48, 89% and 87% of subjects who switched to ATRIPLA maintained HIV RNA <200 copies/mL and <50 copies/mL, respectively, compared to 88% and 85% who remained on SBR; this difference was not statistically significant. No changes in CD4+ cell counts from baseline to Week 48 were observed in either treatment arm.
Other revisions were made to the label for consistency between Sustiva, Viread, Truvada and Emtriva labels.
* Study 934 was an open-label active-controlled study in which 511 antiretroviral-naive patients received either emtricitabine + tenofovir DF administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254).
The complete revised label will be available shortly at Drugs@FDA.