The safety and efficacy of emtri-citabine and tenofovir as combination therapy have not been extensively covered in the literature. As monotherapy, however, each agent has been shown to be effective in the treatment of HIV infection.
GS-0172 was a randomized, open-label, crossover study conducted to evaluate the pharmacokinetics, bioequivalence, and safety of the investigational fixed-dose combination of emtricitabine 200 mg plus tenofovir 300 mg compared with the coadministration of the individual 200-mg emtricitabine capsule and a 300-mg tenofovir tablet in healthy subjects. Forty-four healthy volunteers were enrolled, and 39 completed the study. Blood samples were obtained over 48 hours after each participant received a dose of the study drug following an overnight fast on two occasions, separated by a one-week washout period.
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Results showed that the fixed-dose combination tablet was bioequivalent to the coadministration of the emtricitabine capsule and the tenofovir tablet. Formulation bioequivalence was confirmed if the 90% confidence interval (CI) for the ratio of geometric means for the Cmax and the AUC concentration fell within the range of 80% to 125%. Pharmaco kinetic parameters of emtricitabine and tenofovir were also similar as the fixed-combination tablet and as the emtri-citabine capsule plus tenofovir tablet.
Both regimens were well tolerated, and no serious adverse drug events (ADEs) were reported. Eight subjects (18%) experienced a total of 13 treatment-emergent ADEs, with grade 1 headache being most common (n = 3). Two subjects discontinued the study; one withdrew because of a treatment-related mild rash, and another withdrew because of grade 2 hypertension that was present at baseline but was not considered to be related to the study drug.
FTC-303 was a phase 3, 48-week, randomized, open-label, multicenter study comparing emtricitabine 200 mg once daily with the NRTI lamivudine (3TC, Epivir®, GlaxoSmithKline) 150 mg twice daily, in combination with the NRTI (d4T, Bristol-Myers Squibb Immunology) 40 mg twice daily or the NRTI zidovudine (ZDV, AZT, Retrovir®, GlaxoSmithKline) 300 mg twice daily plus a PI or an NNRTI in 440 patients. The patients were following a lamivudine-containing triple-antiretro-viral regimen for at least 12 weeks before entry into the study, and their HIV RNA levels were below 400 copies/ml. The patients were randomly selected, in a 1:2 ratio, to either continue therapy with lamivudine or to switch to emtricitabine.
At the time of enrollment into the study, the median duration of prior anti-retroviral and lamivudine therapies had been 27.6 and 18 months, respectively. The median HIV RNA level was 1.7 log10 copies/ml, and the mean CD4 cell count was 527 cells/mm3. There were no statistically significant differences between the treatment arms.
GS-99-903 is an ongoing, phase 3, three-year, randomized, double-blind, active-controlled, multicenter clinical trial designed to compare the efficacy and safety of tenofovir 300 mg once daily with stavudine canadian (d4T) 40 mg twice daily with a background regimen of emtricitabine (150 mg twice daily) and the NNRTI (Bristol-Myers Squibb Virology) 600 mg once daily in 600 treatment-naive HIV-infected individuals. At the baseline evaluation, the mean HIV RNA level for the intention-to-treat population was 4.9 log10 copies/ml, and the mean CD4 cell count was 279 cells/mm3. At 48 weeks, similar numbers of patients in both regimens experienced reductions in HIV RNA levels to below 50 and below 400 copies/ml, respectively.