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Semagacestat Pharmacokinetics Are Not Significantly Affected by Formulation, Food, or Time of Dosing in Healthy Participants
Author(s) -
Willis Brian A.,
Zhang Wei,
AyanOshodi Mosun,
Lowe Stephen L.,
Annes William F.,
Sirois Paul J.,
Friedrich Stuart,
Peña Amparo
Publication year - 2012
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 - 10.1177/0091270011407195
Subject(s) - pharmacokinetics , bioavailability , dosing , confidence interval , morning , medicine , evening , crossover study , pharmacodynamics , bioequivalence , cmax , half life , area under the curve , pharmacology , zoology , placebo , physics , alternative medicine , pathology , astronomy , biology
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.