1. Comparison of the Pharmacokinetics of RIPK1 Inhibitor GSK2982772 in Healthy Western and Japanese Subjects
- Author
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Ryutaro Shimamura, Debra J. Tompson, Annette S. Gross, Hirofumi Ogura, Takashi Nagakubo, Nicola Scott, Edward P. Cannons, Hiroko Ino, Atsushi Nakano, Michalis Kostapanos, Carwyn Davies, Marcy Powell, Harue Igarashi, Tompson, Debra J [0000-0003-1030-2611], Davies, Carwyn [0000-0003-0363-3375], Cannons, Edward P [0000-0002-7370-6018], Kostapanos, Michalis [0000-0002-7513-5319], Gross, Annette S [0000-0001-9567-0127], Powell, Marcy [0000-0001-6528-4663], Ino, Hiroko [0000-0002-6793-7944], Shimamura, Ryutaro [0000-0002-7460-7513], Ogura, Hirofumi [0000-0002-8042-6495], Nagakubo, Takashi [0000-0002-8353-0968], Igarashi, Harue [0000-0003-0423-128X], Nakano, Atsushi [0000-0002-6030-0182], and Apollo - University of Cambridge Repository
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Adult ,Male ,medicine.medical_specialty ,Clinical chemistry ,Cmax ,Placebo ,030226 pharmacology & pharmacy ,Drug Administration Schedule ,White People ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Pharmacokinetics ,Asian People ,Double-Blind Method ,Japan ,law ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Original Research Article ,Adverse effect ,Pharmacology ,business.industry ,Middle Aged ,Triazoles ,Healthy Volunteers ,United Kingdom ,Clinical trial ,Oxazepines ,Tolerability ,030220 oncology & carcinogenesis ,Receptor-Interacting Protein Serine-Threonine Kinases ,Female ,business - Abstract
Funder: GlaxoSmithKline; doi: http://dx.doi.org/10.13039/100004330, BACKGROUND AND OBJECTIVES: GSK2982772 is an oral small-molecule RIPK1 inhibitor with potential therapeutic efficacy in immune-mediated inflammatory diseases (IMIDs). An inter-ethnic comparison of GSK2982772 pharmacokinetics was conducted based on data from Western (Study 1) and Japanese subjects (Study 2). METHODS: Both studies were single-centre, randomised, double-blind, placebo-controlled studies with objectives to assess the safety and characterise the pharmacokinetics of GSK2982772. Western subjects in Study 1 (NCT03305419), Part A (N = 15), were randomly assigned to receive 120 mg three times daily (TID), 240 mg TID, or 360 mg twice daily (BID) doses of GSK2982772, or placebo (TID or BID) for 1 day. Part B subjects (N = 47) received GSK2982772 120 mg TID, 240 mg TID, or placebo TID for 14 days. Japanese subjects in Study 2 (N = 13) (NCT03590613) were randomly assigned to receive TID doses of GSK2982772 60, 120, 240 mg TID or placebo TID for 1 day. RESULTS: GSK2982772 was well tolerated and adverse events were generally mild. Maximum observed plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma drug concentration versus time curve after the first GSK2982772 dose (AUC(0-7)) of 120 and 240 mg, and (AUC(0-24)) values for the 120 and 240 mg TID doses over a single day were similar in Japanese and Western subjects. CONCLUSIONS: The pharmacokinetics and tolerability of GSK2982772 were similar between Western and Japanese subjects, justifying inclusion of Japanese subjects in future global clinical studies to assess the therapeutic potential of RIPK1 inhibition for the treatment of IMIDs. Clinical Trials: NCT03305419 and NCT03590613 available from http://www.clinicaltrials.gov .
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- 2020