Results of Two Studies of Pharmacokinetics, Safety, and Bioequivalence of Russian Generic Valsartan / Sacubitril Compared to the Original Valsartan / Sacubitril in Healthy Volunteers

Aim To study the pharmacokinetics and safety and to prove the bioequivalence of Akrivario* (valsartan + sacubitril) film-coated tablets, at two dosages, 200 mg and 100 mg, compared to Uperio** (valsartan + sacubitril) film-coated tablets, at similar dosages, 200 mg and 100 mg (Studies 1 and 2, respectively), after oral administration to fasted healthy volunteers. Material and methods Two four-period, crossover-design bioequivalence studies were conducted. In each study, fasted healthy volunteers (Study 1: n=60; Study 2: n=59) received a single dose of the drugs. The interval between drug administrations was 7 days. Analyte concentrations in blood samples were measured by validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic parameters were determined for both valsartan and sacubitril in both studies. Results The 90% confidence intervals for the Ln-transformed ratios of all assessed pharmacokinetic parameters (Cmax and AUC0-t for valsartan and sacubitril) were in the range of 80-125%. Both study drugs were well tolerated; all adverse events (AEs) were mild and did not require additional therapy. No clinically significant AEs were observed during the study. Conclusion : The study demonstrated bioequivalence of Akrivario (valsartan + sacubitril) to the reference drug Uperio (valsartan + sacubitril).