Comparison of the Pharmacokinetics of RIPK1 Inhibitor GSK2982772 in Healthy Western and Japanese Subjects.
Adult
Asian People
/ ethnology
Double-Blind Method
Drug Administration Schedule
Female
Healthy Volunteers
Humans
Japan
/ ethnology
Male
Middle Aged
Oxazepines
/ administration & dosage
Receptor-Interacting Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Triazoles
/ administration & dosage
United Kingdom
/ ethnology
White People
/ ethnology
Journal
European journal of drug metabolism and pharmacokinetics
ISSN: 2107-0180
Titre abrégé: Eur J Drug Metab Pharmacokinet
Pays: France
ID NLM: 7608491
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
pubmed:
10
11
2020
medline:
24
9
2021
entrez:
9
11
2020
Statut:
ppublish
Résumé
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). 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. GSK2982772 was well tolerated and adverse events were generally mild. Maximum observed plasma drug concentration (C 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 .
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
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
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
RESULTS
GSK2982772 was well tolerated and adverse events were generally mild. Maximum observed plasma drug concentration (C
CONCLUSIONS
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 .
Identifiants
pubmed: 33165774
doi: 10.1007/s13318-020-00652-2
pii: 10.1007/s13318-020-00652-2
pmc: PMC7811991
doi:
Substances chimiques
GSK2982772
0
Oxazepines
0
Triazoles
0
RIPK1 protein, human
EC 2.7.11.1
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Banques de données
ClinicalTrials.gov
['NCT03590613', 'NCT03305419']
Types de publication
Comparative Study
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-83Références
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