Safety, tolerability, QTc evaluation, and pharmacokinetics of single and multiple doses of enzastaurin HCl (LY317615), a protein kinase C-beta inhibitor, in healthy subjects.

Abstract:

:The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and its metabolites ranged from approximately 12 to 40 hours. The longer half-life of the major circulating and pharmacologically active metabolite allowed once-a-day dosing and predicted that steady state would be achieved within 2 weeks of daily oral dosing in all subjects. In the multiple-dose study, daily doses (25-400 mg) were examined, with 24 subjects receiving at least 1 dose. The most common adverse events related to enzastaurin were headache, sleepiness, diarrhea, and nausea. No clinically significant changes in QTc intervals were observed. Overall, enzastaurin was well tolerated in healthy subjects, and the planned maximum dose was achieved in both studies.

journal_name

J Clin Pharmacol

authors

Welch PA,Sinha VP,Cleverly AL,Darstein C,Flanagan SD,Musib LC

doi

10.1177/0091270007304775

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

1138-51

issue

9

eissn

0091-2700

issn

1552-4604

pii

47/9/1138

journal_volume

47

pub_type

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