GENVOYA(elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)tablets(七)
actions* (All Grades) Reported in ≥ 5% of HIV-1 Infected Treatment-Naïve Adults Receiving GENVOYA in Studies 104 and 111 (Week 96 analysis)
GENVOYA
N=866 STRIBILD
N=867
* Frequencies of adverse reactions are based on all adverse events attributed to study drugs by the investigator.
GASTROINTESTINAL DISORDERS
Diarrhea 7% 9%
Nausea 10% 13%
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Fatigue 5% 4%
NERVOUS SYSTEM DISORDERS
Headache 6% 5%
The majority of events presented in Table 2 occurred at severity Grade 1.
Clinical Trials in Virologically Suppressed Adults
The safety of GENVOYA in virologically-suppressed adults was based on Week 96 data from 959 subjects in a randomized, open-label, active-controlled trial (Study 109) in which virologically-suppressed subjects were switched from a TDF-containing combination regimen to GENVOYA. Overall, the safety profile of GENVOYA in subjects in this study was similar to that of treatment-naïve subjects [see CLINICAL STUDIES (14.3)]. Additional adverse reactions observed with GENVOYA in Study 109 included suicidal ideation, suicidal behavior, and suicide attempt (<1% combined); all of these events were serious and all occurred in subjects with a preexisting history of depression or psychiatric illness.
Clinical Trials in Adult Subjects with Renal Impairment
In an open-label trial (Study 112), 248 HIV-1 infected subjects with eGFR of 30 to 69 mL per minute (by Cockcroft-Gault method) were treated with GENVOYA for a median duration of 108 weeks. Of these subjects, 65% had previously been on a stable TDF-containing regimen. A total of 5 subjects permanently discontinued GENVOYA due to the development of renal adverse events. Three of these five were among the 80 subjects with baseline eGFRs of < 50mL/min and two subjects were among the 162 subjects with baseline eGFRs of ≥ 50mL/min. One additional subject with baseline eGFR of ≥ 50mL/min developed acute renal failure. Following a brief interruption, GENVOYA was resumed and this subject's renal function returned to baseline. Overall, renally impaired subjects receiving GENVOYA in this study had a mean serum creatinine of 1.5 mg/dL at baseline and 1.4 mg/dL at Week 96. Otherwise, the safety profile of GENVOYA in subjects in this study was similar to that of subjects with normal renal function [see CLINICAL STUDIES (14.4)].
Renal Laboratory Tests and Renal Safety
Treatment-Naïve Adults:
Cobicistat (a component of GENVOYA) has been shown to increase serum creatinine due to inhibition of tubular secretion of creatinine without affecting glomerular filtration [see CLINICAL PHARMACOLOGY (12.2)]. Increases in serum creatinine occurred by Week 2 of treatment and remained stable through 96 weeks.
In two 96-week randomized, controlled trials in a total of 1,733 treatment-naïve adults with a median baseline eGFR of 115 mL per minute, mean serum creatinine increased by less than 0.1 mg per dL in the GENVOYA group and by 0.1 mg per dL in the STRIBILD group from baseline to Week 96.
Virologically Suppressed Adults:
In a study of 1,436 virologically-suppressed TDF-treated adults with a mean baseline eGFR of 112 mL per minute who were randomized to continue their treatment regimen or switch to GENVOYA, at Week 96 mean serum creatinine was similar to base |