Bioequivalence study of a new fixed-dose combination of valsartan and indapamide (modified-release tablets) versus concomitant administration of the respective reference single-ingredient products

Le résumé fourni par la source

Aim . Тo evaluate the bioequivalence of Valsartan + Indapamide 160 mg + 1.5 mg modified release tablets developed by Gedeon Richter Polska Sp. z o. o. (Poland) compared to the reference products Diovan® (Siegfried Barbera S.L. (formerly Novartis Farmaceutica S.A.), Spain) coadministered with Arifon® Retard (Servier RUS LLC, Russia). Material and methods. Three randomised, single-centre, open-label, crossover studies with two sequences were conducted in a population of healthy adult volunteers of both sexes aged 18–45 years who met the inclusion criteria and had no exclusion criteria. Study A included four periods assessing single-dose administration under fasting conditions (n=56), Study B included two periods assessing single-dose administration under fed conditions (n=52), and Study C included two periods assessing multiple-dose administration under fasting conditions (n=52). The washout period was at least 14 days between all periods. Plasma concentrations were determined using validated analytical methods of high-performance liquid chromatography and tandem mass spectrometry. However, as valsartan was not modified release its exposure was not measured in all studies. Pharmacokinetic parameters including AUC0-inf, Cmax and AUC0-t in study A and B, and AUC0-τ, Cmax,ss and Cτ,ss in study C were determined using non-compartmental analysis. Bioequivalence was concluded if the 90% confidence intervals for the test/reference ratios of given parameters fell within the 80.00-125.00% range, except for Study A valsartan Cmax parameter, where the range was widened to 78.05-128.13%. Results . In Study A, the GMRs for AUC0-t and Cmax were 105.97% and 108.15% for indapamide and 104.07% and 104.15% for valsartan, respectively.In Study B, GMRs for the specified parameters for indapamide were 101.03% and 96.47%. In Study C, the GMR values for AUC0-τ and Cmax,ss were 109.69% and 111.75% for indapamide. All 90% confidence intervals were within the predefined bioequivalence limits. The drug was well tolerated. Only mild and well-known treatment-emergent adverse events were reported, without any treatment discontinuation. Conclusions . The fixed dose combination of valsartan and indapamide 160 mg + 1.5 mg, modified released tablets manufactured by Gedeon Richter Polska Sp. z o. o. is bioequivalent to Diovan® co-administered with Arifon® Retard, and is safe and well tolerated. The results support the use of this fixed dose combination as an effective alternative to the concurrent administration of the reference products for the treatment of hypertension

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.