Comparison of Two Manufacturing Processes of Daprodustat for Bioequivalence and Dissolution in Healthy Volunteers: A Randomized Crossover Study.

Autor: Shaddinger B; GSK, Collegeville, Pennsylvania, USA., Mahar KM; GSK, Collegeville, Pennsylvania, USA., Sprys M; GSK, Collegeville, Pennsylvania, USA., Andrews SM; Global Clinical Operations Development R&D, GSK, Research Triangle Park, Durham, North Carolina, USA., Chattoraj S; GSK, Collegeville, Pennsylvania, USA., Israni R; GSK, Collegeville, Pennsylvania, USA., Cobitz A; GSK, Collegeville, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2023 Jul; Vol. 12 (7), pp. 739-748. Date of Electronic Publication: 2023 May 01.
DOI: 10.1002/cpdd.1257
Abstrakt: Daprodustat, an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase enzyme inhibitor, has recently completed phase 3 clinical development for treating anemia of chronic kidney disease. Part A of this 2-part, randomized, double-blind, single-dose, cross-over study (NCT04640311) compared pharmacokinetic properties of a single oral dose of daprodustat 4 mg tablets manufactured via twin-screw wet granulation (process 1) to 2 sets of 4 mg tablets manufactured via high-shear wet granulation (process 2), to assess the impact of different dissolution profiles on pharmacokinetics. Part B assessed the bioequivalence of daprodustat tablets manufactured via process 1 with tablets manufactured via process 2 at 5 different dose strengths (1, 2, 4, 6, and 8 mg). In part A, mean plasma concentrations of daprodustat were comparable over a 24-hour period despite differences in manufacturing processes and dissolution profiles. In part B, the 90% confidence intervals of the ratios of the least squared means for area under the concentration-time curve and maximum observed plasma concentration fell within the 0.8-1.25 bioequivalence range for all doses, except for maximum observed plasma concentration at 8 mg. A prespecified sensitivity analysis jointly assessing all doses showed bioequivalence for all doses tested. No new safety concerns for daprodustat were identified.
(© 2023 GSK. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
Databáze: MEDLINE
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