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Bioequivalence of a generic medicinal product Tiara Duo (valsartan and hydrochlorothiazide fixed-dose combination) to the reference medicinal product Co-Diovan®: results of a randomized crossover clinical trial in healthy volunteers

September 23, 2019
948
Cardiology, Rheumatology
Therapy, General practice
Kravchuk Zh.
Artysh B.
Doroshenko A.
Sabko V.
Sotnychenko N.M.
Keywords :
bioequivalence,
generic,
healthy volunteers,
hydrochlorothiazide,
reference drug,
tablets,
valsartan
Specialities :
Cardiology, Rheumatology
Therapy, General practice
Resume

The aim is to prove the bioequivalence of the test medicinal product Tiara Duo, 160 mg valsartan/25 mg hydrochlorothiazide film-coated tablets (PrJSC «Pharmaceutical Firm «Darnitsa», Ukraine), and the reference medicinal product Co-Diovan®, 160 mg valsartan/25 mg hydrochlorothiazide film-coated tablets («Novartis Pharmaceuticals UK LTD», United Kingdom) in a comparative randomized four-period two-sequence (TRTR/RTRT) crossover clinical trial in healthy volunteers. Materials and methods. During each period, male volunteers took 1 tabl. of the test or reference medicinal product in the fasting condition. Blood samples were taken within 36 hours. Quantitative determination of valsartan and hydrochlorothiazide in blood plasma was performed using ultra-performance liquid chromatography with tandem mass-selective detection. Results. Data from 34 healthy volunteers were included in the analysis of pharmacokinetics. For Tiara Duo and Co-Diovan®, mean Cmax values were 3460.6±1580.9 and 3293.5±1717.9 ng/mL (for valsartan) and 158.16±92.50 and 162.40±94.09 ng/mL (for hydrochlorothiazide), respectively. Mean valsartan and hydrochlorothiazide AUC0–t values were 19508.75±9079.00 and 1095.55±655.50 ng‧h/mL for the test medicinal product and 18175.84±9537.15 and 1115.35±666.47 ng‧h/mL, for the reference medicinal product, respectively. The ranges of 90% confidence intervals of geometric mean ratio for 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 Tiara Duo and Co-Diovan® meet prespecified acceptance criteria for bioequivalence (80.00–125.00%). Suspected adverse reactions were reported in 2 vo­lunteers and were considered to be non-serious. Conclusions. The bioequivalence of generic medicinal product Tiara Duo, 160 mg valsartan/25 mg hydrochlorothiazide film-coated tablets, and the reference medicinal product Co-Diovan®, 160 mg valsartan/25 mg hydrochlorothiazide film-coated tablets, was proven. Both drugs were reported to have comparable tolerability and safety following a single dose oral administration in the fasting state.

Published: 23.09.2019

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