Bioequivalence of the generic product TiaraDuo (fixed combination of valsartan and hydrochlorothiazide) to the reference medicinal product Co-Diovan®28 September 2019
Purpose. to prove the bioequivalence of the test medicinal product Tiara Duo, film-coated tablets, 160 mg valsartan/ 25 mg hydrochlorothiazide, manufactured by PrJSC “Pharmaceutical Firm “Darnitsa” (Ukraine), to the reference medicinal product Co-Diovan®, film-coated tablets, 160 mg valsartan/ 25 mg hydrochlorothiazide, manufactured by Novartis Pharmaceuticals UK LTD (United Kingdom) in a comparative randomized crossover, two-sequence, four-period study (according to the TRTR/RTRT scheme) in healthy volunteers.
Object and methods of the study. Male volunteers administered one tablet of the test and reference medicinal products once on an empty stomach during each period. Blood samples were collected within 36 hours. The plasma concentrations of valsartan and hydrochlorothiazide in volunteers were measured using ultra-performance liquid chromatography with tandem mass-spectrometric detection (UPLC-MS/MS). Results. Pharmacokinetic analysis included data from 34 healthy volunteers. The mean Сmax values for the test medicinal product Tiara Duo® and the reference product Co-Diovan® were 3460.6±1580.9 ng/ml and 3293.5±1717.9 ng/ml (for valsartan) and 158.16±92.50 ng/ml and 162.40±94.09 ng/ml (for hydrochlorothiazide), respectively. The mean AUC0–t values of valsartan and hydrochlorothiazide were respectively 19508.75 ± 9079.00 ng h/ml and 1095.55 ± 655.50 ng‧h/ml for the test medicinal product and 18175.84 ± 9537.15 ng‧h/ml and 1115.35 ± 666.47 ng h/ml for the reference medicinal product, respectively. 90% confidence interval limits for ratios of geometric means of Cmax (97.33–123.22% for valsartan and 91.78–104.74% for hydrochlorothiazide) and AUC0–t (100.25–122.52% for valsartan and 92.68–103.83% for hydrochlorothiazide) for the medicinal product Tiara Duo and Co-Diovan® meet the predefined acceptance criterion for bioequivalence (80.00%–125.00%). The suspected adverse reactions were observed in 2 volunteers and were considered non-serious.
Conclusions. The study proved the bioequivalence of the generic medicinal product Tiara Duo, film-coated tablets, 160 mg valsartan/ 25 mg hydrochlorothiazide to the reference medicinal product Co-Diovan®, film-coated tablets, 160 mg valsartan/ 25 mg hydrochlorothiazide. Both medicinal products were characterized with comparable tolerability and safety with single oral dosage on an empty stomach.The sponsor of the study, PrJSC “Pharmaceutical Firm “Darnitsa” expresses its gratitude to the employees of INNOPHAR – Ukraine Innovative Pharma Research Clinic Ltd (Ukraine) and the bioanalytical laboratory of Clinfarm LLC (Ukraine) for conducting the research and processing its results.