Emtricitabine clinical studies

# 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 1880), 86% were male, 59% were Caucasian and 23% were Black. The mean baseline CD4+ cell count was 245 cells/mm3 (range 21191) and median baseline plasma HIV-1 RNA was 5.01 log10 copies/mL (range 3.566.54). Subjects were stratified by baseline CD4+ cell count (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.
Through Week 48, 84% and 73% of subjects in the EMTRIVA + tenofovir DF group and the zidovudine/lamivudine group, respectively, achieved and maintained HIV-1 RNA <400 copies/mL (71% and 58% through Week 144). The difference in the proportion of subjects who achieved and maintained HIV-1 RNA <400 copies/mL through 48 weeks largely results from the higher number of discontinuations due to adverse events and other reasons in the zidovudine/lamivudine group in this open-label trial. In addition, 80% and 70% of subjects in the EMTRIVA + tenofovir DF group and the zidovudine/lamivudine group, respectively, achieved and maintained HIV-1 RNA <50 copies/mL through Week 48 (64% and 56% through Week 144). The mean increase from baseline in CD4+ cell count was 190 cells/mm3 in the EMTRIVA + tenofovir DF group and 158 cells/mm3 in the zidovudine/lamivudine group at Week 48 (312 and 271 cells/mm3 at Week 144).
Through 48 weeks, 7 subjects in the EMTRIVA + tenofovir DF group and 5 subjects in the zidovudine/lamivudine group experienced a new CDC Class C event (10 and 6 subjects through 144 weeks).

### Study 301A
Study 301A was a 48 week double-blind, active-controlled multicenter clinical trial comparing EMTRIVA (200 mg once daily) administered in combination with didanosine and efavirenz versus stavudine, didanosine and efavirenz in 571 antiretroviral naive adult subjects. Subjects had a mean age of 36 years (range 1869), 85% were male, 52% Caucasian, 16% African-American and 26% Hispanic. Subjects had a mean baseline CD4+ cell count of 318 cells/mm3 (range 51317) and a median baseline plasma HIV-1 RNA of 4.9 log10 copies/mL (range 2.67.0). Thirty-eight percent of subjects had baseline viral loads >100,000 copies/mL and 31% had CD4+ cell counts <200 cells/mL. Treatment outcomes are presented in Table 11 below.
The mean increase from baseline in CD4+ cell count was 168 cells/mm3 for the EMTRIVA arm and 134 cells/mm3 for the stavudine arm.
Through 48 weeks in the EMTRIVA group, 5 subjects (1.7%) experienced a new CDC Class C event, compared to 7 subjects (2.5%) in the stavudine group.

## Treatment-Experienced Adult Patients

### Study 303
Study 303 was a 48 week, open-label, active-controlled multicenter clinical trial comparing EMTRIVA (200 mg once daily) to lamivudine, in combination with stavudine or zidovudine and a protease inhibitor or NNRTI in 440 adult subjects who were on a lamivudine-containing triple-antiretroviral drug regimen for at least 12 weeks prior to trial entry and had HIV-1 RNA 400 copies/mL.
Subjects were randomized 1:2 to continue therapy with lamivudine (150 mg twice daily) or to switch to EMTRIVA (200 mg once daily). All subjects were maintained on their stable background regimen. Subjects had a mean age of 42 years (range 2280), 86% were male, 64% Caucasian, 21% African-American and 13% Hispanic. Subjects had a mean baseline CD4+ cell count of 527 cells/mm3 (range 371909), and a median baseline plasma HIV-1 RNA of 1.7 log10 copies/mL (range 1.74.0).
The median duration of prior antiretroviral therapy was 27.6 months. Treatment outcomes are presented in Table 12 below.
The mean increase from baseline in CD4+ cell count was 29 cells/mm3 for the EMTRIVA arm and 61 cells/mm3 for the lamivudine arm.
Through 48 weeks, in the EMTRIVA group 2 subjects (0.7%) experienced a new CDC Class C event, compared to 2 subjects (1.4%) in the lamivudine group.

### Pediatric Patients
In three open-label, non-randomized clinical trials, emtricitabine was administered to 169 HIV-1 infected treatment-naive and experienced (defined as virologically suppressed on a lamivudine containing regimen for which emtricitabine was substituted for lamivudine) subjects between 3 months and 21 years of age. Subjects received once-daily EMTRIVA oral solution (6 mg/kg to a maximum of 240 mg/day) or EMTRIVA capsules (a single 200 mg capsule once daily) in combination with at least two other antiretroviral agents.
Subjects had a mean age of 7.9 years (range 0.321), 49% were male, 15% Caucasian, 61% Black and 24% Hispanic. Subjects had a median baseline HIV-1 RNA of 4.6 log10 copies/mL (range 1.76.4) and a mean baseline CD4+ cell count of 745 cells/mm3 (range 22650). Through 48 weeks of therapy, the overall proportion of subjects who achieved and sustained an HIV-1 RNA <400 copies/mL was 86%, and <50 copies/mL was 73%. The mean increase from baseline in CD4+ cell count was 232 cells/mm3 (-945, +1512). The adverse reaction profile observed during these clinical trials was similar to that of adult subjects, with the exception of the occurrence of anemia and higher frequency of hyperpigmentation in children.
The pharmacokinetics of emtricitabine were studied in 20 neonates born to HIV-1-positive mothers. Each mother received prenatal and intrapartum combination antiretroviral therapy. Neonates received up to 6 weeks of zidovudine prophylactically after birth. The neonates were administered two short courses of emtricitabine oral solution (each 3 mg/kg once daily  4 days) during the first 3 months of life. Emtricitabine exposures in neonates were similar to the exposures achieved in subjects ages 3 months to 17 years . During the two short dosing periods on emtricitabine there were no safety issues identified in the treated neonates. All neonates were HIV-1 negative at the end of the trial; the efficacy of emtricitabine in preventing or treating HIV-1 could not be determined.