Summary of bioequivalence study for TIARA SOLO®, 80 mg valsartan film-coated tablets; 160 mg valsartan film-coated tablets
24 January 2023Purpose. To prove the bioequivalence (BE) of the test investigational medicinal product (IMP) TIARA SOLO®, 160 mg valsartan film-coated tablets, manufactured by PrJSC “Pharmaceutical Firm “Darnitsa” (Ukraine) to the reference IMP DIOVAN®, 160 mg valsartan film-coated tablets, manufactured by Novartis Farmaceutica S.A. (Spain) in a randomized, open-label, crossover, comparative single-dose, four-period, two-sequence oral bioequivalence study in 40 healthy male and female volunteers under fasting conditions.
Objects and methods of the study. Healthy male and female volunteers took a single oral dose of test or reference IMPs, i.e., 160 mg of valsartan, in each period (i.e., 640 mg of valsartan throughout the study) under fasting conditions. Data of 39 healthy volunteers fully completed the study according to the protocol and taken IMP in all four periods (two times Test and two times Reference IMPs) were included in pharmacokinetic and statistical analysis.
Results. Pharmacokinetic results demonstrated that geometric least squares means ratios and corresponding 90% confidence intervals (CIs) of valsartan maximum plasma concentration (Cmax), area under the plasma concentration curve from administration to last observed concentration at time t (AUC0-t) and area under the plasma concentration curve extrapolated to infinite time (AUC0-∞) were 100.27% (92.52 – 108.67%), 101.77% (94.43 – 109.69%) and 101.76% (94.55 – 109.51%), respectively. The criteria used to assess bioequivalence between Test and Reference IMPs were all fulfilled since Test to Reference ratio of geometric least squares means and corresponding 90% CIs for Cmax, AUC0-t and AUC0-∞ were all within acceptance range of 80.00 to 125.00%.
During the study, only non-serious adverse events (AEs) of mild and moderate severity were recorded. Overall, an oral single dose of 160 mg valsartan (Reference and Test) administered to healthy volunteers in the fasted state was well tolerated. No serious adverse events (SAEs) were reported for any of the subjects enrolled in the study.
Conclusions. The bioequivalence of the test IMP (TIARA SOLO®, 160 mg valsartan film-coated tablets) to the reference IMP (DIOVAN®, 160 mg valsartan film-coated tablets) was demonstrated in this study. Both IMPs were characterized to have good tolerability with single (within each period) oral administration under fasting conditions.
The Sponsor of the study, PrJSC “Pharmaceutical Firm “Darnitsa”, expresses its gratitude to the employees of Clinical Diagnostic Center “Pharmbiotest” LLC (Rubizhne, Ukraine) for conducting the research and processing its results.
For more details about study design, please see Annex 30 published on the official site of the State Expert Center of the Ministry of Health of Ukraine: https://www.dec.gov.ua/wp-content/uploads/2021/reportClinical/11/8.pdf.