Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
In long-term oral carcinogenicity studies of emtricitabine, no drug-related increases in tumor incidence were found in mice at doses up to 750 mg/kg/day (26 times the human systemic exposure at the therapeutic dose of 200 mg/day) or in rats at doses up to 600 mg/kg/day (31 times the human systemic exposure at the therapeutic dose).

Emtricitabine was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or mouse micronucleus assays.

Emtricitabine did not affect fertility in male rats at approximately 140-fold or in male and female mice at approximately 60-fold higher exposures (AUC) than in humans given the recommended 200 mg daily dose. Fertility was normal in the offspring of mice exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60-fold higher than human exposures at the recommended 200 mg daily dose.

Clinical Studies
Treatment-Naive Adult Patients
Study 934

Data through 144 weeks are reported for Study 934, a randomized, open-label, active-controlled multicenter clinical trial comparing Emtriva + tenofovir disoproxil fumarate (tenofovir DF) administered in combination with efavirenz versus zidovudine/lamivudine fixed-dose combination administered in combination with efavirenz in 511 antiretroviral-naive subjects. From Weeks 96 to 144 of the trial, subjects received Emtriva/tenofovir DF fixed-dose combination with efavirenz in place of Emtriva + tenofovir DF with efavirenz. Subjects had a mean age of 38 years (range 18–80), 86% were male, 59% were Caucasian and 23% were Black. The mean baseline CD4+ cell count was 245 cells/mm3 (range 2–1191) and median baseline plasma HIV-1 RNA was 5.01 log10 copies/mL (range 3.56–6.54). Subjects were stratified by baseline CD4+ cell count (< or ≥200 cells/mm3); 41% had CD4+ cell counts <200 cells/mm3 and 51% of subjects had baseline viral loads >100,000 copies/mL. Treatment outcomes through 48 and 144 weeks for those subjects who did not have efavirenz resistance at baseline are presented in Table 10.

Table 10 Outcomes of Randomized Treatment at Week 48 and 144 (Study 934) Outcomes Week 48 Week 144
Emtriva
+TDF
+EFV
(N=244) AZT/3TC
+EFV
(N=243) Emtriva
+ TDF
+EFV
(N=227)* AZT/3TC
+EFV
(N=229)*
*
Subjects who were responders at Week 48 or Week 96 (HIV-1 RNA <400 copies/mL) but did not consent to continue in the trial after Week 48 or Week 96 were excluded from analysis.
†
Subjects achieved and maintained confirmed HIV-1 RNA <400 copies/mL through Weeks 48 and 144.
‡
Includes confirmed viral rebound and failure to achieve confirmed <400 copies/mL through Weeks 48 and 144.
§
Includes lost to follow-up, subject withdrawal, noncompliance, prot