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Semagacestat pharmacokinetics are not significantly affected by formulation, food, or time of dosing in healthy participants.

Abstract：

:Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first study (n = 14) compared tablet to capsules. For all formulations, the median time to maximum plasma concentration (t(max)) was generally 1.0 hour. Plasma elimination was rapid, with a half-life of approximately 2.5 hours. Tablet form II bioavailability (F) relative to capsule was approximately 100% (F = 1.03 [90% confidence interval (CI), 0.96-1.10]). In the second study, participants (n = 27) received semagacestat either fed or fasting in the morning or fasting in the evening. No significant change in exposure (AUC(0-∞) [area under the concentration-time curve from 0 to infinity] ratio = 1.02, [90% CI, 0.990-1.05]) occurred with food, whereas maximum plasma concentration (C(max)) declined approximately 15%, and median t(max) was delayed to 1.5 hours. Time of dosing made no significant difference in AUC(0-∞), C(max), or t(max) (AUC(0-∞) ratio 1.01, [90% CI, 0.975-1.04]). No clinically significant safety concerns occurred in either study. Accordingly, semagacestat may be dosed without regard to formulation, food, or time of administration.

journal_name

J Clin Pharmacol

journal_title

Journal of clinical pharmacology

authors

Willis BA,Zhang W,Ayan-Oshodi M,Lowe SL,Annes WF,Sirois PJ,Friedrich S,de la Peña A

doi

10.1177/0091270011407195

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

904-13

issue

6

eissn

0091-2700

issn

1552-4604

pii

0091270011407195

journal_volume

52

pub_type

临床试验,杂志文章,随机对照试验

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