GENVOYA(elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)tablets(二十九)
atment. At the high dose in female mice, liver adenomas were increased at tenofovir exposures 10 times (300 mg TDF) and 167 times (10 mg TAF in GENVOYA) that in humans. In rats, the study was negative for carcinogenic findings.
TAF was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or rat micronucleus assays.
There were no effects on fertility, mating performance or early embryonic development when TAF was administered to male rats at a dose equivalent to 155 times the human dose based on body surface area comparisons for 28 days prior to mating and to female rats for 14 days prior to mating through Day 7 of gestation.
13.2 Animal Toxicology and/or Pharmacology
Minimal to slight infiltration of mononuclear cells in the posterior uvea was observed in dogs with similar severity after three and nine month administration of TAF; reversibility was seen after a three month recovery period. At the NOAEL for eye toxicity, the systemic exposure in dogs was 5 (TAF) and 15 (tenofovir) times the exposure seen in humans at the recommended daily GENVOYA dosage.
14 CLINICAL STUDIES
14.1 Description of Clinical Trials
The efficacy and safety of GENVOYA were eva luated in the studies summarized in Table 12.
Table 12 Trials Conducted with GENVOYA in Subjects with HIV-1 Infection
Trial Population Study Arms (N) Timepoint (Week)
* Randomized, double blind, active controlled trial. † Randomized, open label, active controlled trial. ‡ HIV-1 RNA less than 50 copies per mL. § Open label trial. ¶ eGFR of 30 to 69 mL per minute by Cockcroft-Gault method.
Study 104*
Study 111* Treatment-naïve adults GENVOYA (866)
STRIBILD (867) 96
Study 109† Virologically-suppressed‡ adults GENVOYA (959)
ATRIPLA® or TRUVADA®+atazanavir+cobicistat or ritonavir or STRIBILD (477) 96
Study 112§ Virologically-suppressed‡ adults with renal impairment¶ GENVOYA (242) 96
Study 106§ Treatment-naïve adolescents between the ages of 12 to less than 18 years GENVOYA (50) 48
14.2 Clinical Trial Results in HIV-1 Treatment-Naïve Subjects
In both Study 104 and Study 111, subjects were randomized in a 1:1 ratio to receive either GENVOYA (N=866) once daily or STRIBILD (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, TDF 300 mg) (N=867) once daily. The mean age was 36 years (range 18–76), 85% were male, 57% were White, 25% were Black, and 10% were Asian. Nineteen percent of subjects identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.5 log10 copies per mL (range 1.3–7.0) and 23% of subjects had baseline viral loads greater than 100,000 copies per mL. The mean baseline CD4+ cell count was 427 cells per mm3 (range 0–1360) and 13% had CD4+ cell counts less than 200 cells per mm3.
Pooled treatment outcomes of Studies 104 and 111 through Week 96 are presented in Table 13.
Table 13 Pooled Virologic Outcomes of Randomized Treatment in Studies 104 and 111 at Week 96* in Treatment-Naïve Subjects
GENVOYA
(N=866) STRIBILD
(N=867)
* Week 96 window was between Day 630 and 713 (inclusive). † Included subjects who had ≥50 copies/mL in the Week 96 window; subjects who discontinued early due to lack or loss of efficacy; subjects who discontinued for reasons other than an adverse event (AE), death |
