Premium
Safety, Tolerability, QTc Evaluation, and Pharmacokinetics of Single and Multiple Doses of Enzastaurin HCl (LY317615), a Protein Kinase C‐β Inhibitor, in Healthy Subjects
Author(s) -
Welch Pamela A.,
Sinha Vikram P.,
Cleverly Ann L.,
Darstein Christelle,
Flanagan Shawn D.,
Musib Luna C.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007304775
Subject(s) - tolerability , pharmacokinetics , dosing , medicine , adverse effect , nausea , pharmacology , active metabolite , placebo , qt interval , anesthesia , alternative medicine , pathology
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.