Relative Bioavailability of Omecamtiv Mecarbil Pediatric Minitablet Formulations in Healthy Adult Subjects.
Administration, Oral
Adolescent
Adult
Biological Availability
Cross-Over Studies
Delayed-Action Preparations
/ chemistry
Drug Compounding
Female
Half-Life
Healthy Volunteers
Heart Failure
/ drug therapy
Humans
Male
Middle Aged
Myalgia
/ etiology
Tablets
/ chemistry
Urea
/ adverse effects
Young Adult
Journal
Clinical drug investigation
ISSN: 1179-1918
Titre abrégé: Clin Drug Investig
Pays: New Zealand
ID NLM: 9504817
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
accepted:
28
05
2021
pubmed:
11
6
2021
medline:
11
8
2021
entrez:
10
6
2021
Statut:
ppublish
Résumé
Omecamtiv mecarbil (OM) is a cardiac myosin activator under clinical development for the treatment of heart failure. Two modified-release (MR) novel OM minitablet formulations were developed to support the planned investigation of chronic heart failure in pediatric patients. The primary objective of this study was to determine the bioavailability of the minitablets relative to the adult matrix MR formulation tablets. In a randomized, 5-period, crossover study, 20 healthy subjects received each of the following treatments orally: one 25-mg adult matrix MR tablet, 25 1-mg slow-release minitablets, 25 1-mg fast-release minitablets, six 1-mg slow-release minitablets, or six 1-mg fast-release minitablets after an overnight fast of at least 10 h with a minimum washout of 7 days between treatments. Blood samples were collected for up to 168 h. OM pharmacokinetic parameters were estimated using non-compartmental methods. When OM was administered as 25 1-mg OM slow-release minitablets, AUC Relative bioavailability of slow-release minitablets was demonstrated to be similar to the adult matrix MR formulation.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
Omecamtiv mecarbil (OM) is a cardiac myosin activator under clinical development for the treatment of heart failure. Two modified-release (MR) novel OM minitablet formulations were developed to support the planned investigation of chronic heart failure in pediatric patients. The primary objective of this study was to determine the bioavailability of the minitablets relative to the adult matrix MR formulation tablets.
METHODS
METHODS
In a randomized, 5-period, crossover study, 20 healthy subjects received each of the following treatments orally: one 25-mg adult matrix MR tablet, 25 1-mg slow-release minitablets, 25 1-mg fast-release minitablets, six 1-mg slow-release minitablets, or six 1-mg fast-release minitablets after an overnight fast of at least 10 h with a minimum washout of 7 days between treatments. Blood samples were collected for up to 168 h. OM pharmacokinetic parameters were estimated using non-compartmental methods.
RESULTS
RESULTS
When OM was administered as 25 1-mg OM slow-release minitablets, AUC
CONCLUSIONS
CONCLUSIONS
Relative bioavailability of slow-release minitablets was demonstrated to be similar to the adult matrix MR formulation.
Identifiants
pubmed: 34110614
doi: 10.1007/s40261-021-01052-3
pii: 10.1007/s40261-021-01052-3
doi:
Substances chimiques
Delayed-Action Preparations
0
Tablets
0
omecamtiv mecarbil
2M19539ERK
Urea
8W8T17847W
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
639-645Références
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