Pharmacodynamics of ASP8477 Clinical Trial
Official title:
A Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of ASP8477 in Healthy Postmenopausal Females and Healthy Young Vasectomized Males, Including a Food Effect Part and a Part to Investigate the Interaction Between ASP8477 and Omeprazole
This is a 4-part study. Part I assesses the safety and tolerability of single ascending
doses of ASP8477 or a placebo under fasted conditions in postmenopausal subjects. Part II is
similar to part I except that the study is conducted in young, vasectomized males.
Part III assesses the effect of food (fed or fasted conditions) on ASP8477 in postmenopausal
subjects.
Part IV assesses the drug-drug interaction between ASP8477 and omeprazole in postmenopausal
subjects.
Part I (SAD) in healthy postmenopausal females evaluates the safety, and tolerability, and
defines Maximum Tolerated Dose = MTD, pharmacokinetics, and pharmacodynamics of single
ascending oral doses (SAD) of ASP8477. It is anticipated that around 7 doses are required to
cover the range from the safe starting dose until the MTD. Study medication is administered
under fasted conditions. Based on the safety, PK, and clinical observation of the subjects,
the dose escalation scheme may be adapted. Escalation to the next dose only proceeds after
review of the safety, tolerability, and PK from the previous treatment period.
Part II (SAD in young, healthy, vasectomized males) is similar to Part I, one cohort of 12
subjects are treated with two doses of ASP8477 plus placebo. The doses tested depend on the
safety data and pharmacodynamic profiles obtained in Part I, but is not expected to exceed
MTD. The rationale for this part is to bridge the data obtained in female subjects to male
subjects.
Part III (food effect) postmenopausal females receive ASP8477 once under fasted and once
under fed conditions in two separate periods in random order. The dose does not exceed 1/3
of the MTD or, if that has not been reached, 1/3 of the highest tested dose in Part I.
Subjects stay in the clinic for 2 periods of 5 to 7 days (depending on the terminal half
life, resulting from Part I). Subjects are admitted on Day -2 per treatment period.
Subjects' feeding status is the same as on Day 1 of the same treatment period. Subjects are
given a single dose of ASP8477 under fed or fasting conditions on Day 1. After final
discharge, subjects return for an End of Study Visit (ESV) 5-9 days later.
Part IV (ASP8477-omeprazole drug-drug interaction) postmenopausal subjects are randomized to
receive omeprazole once alone and once with ASP8477 in two separate periods (in random
order). The dose of ASP8477 is the MTD or, if that is not been reached, the highest tested
dose in Part I. Omeprazole is chosen as target drug as it is a model substrate for CYP2C19
(accepted by FDA) and ASP8477 is known to have the strongest inhibitory effect on CYP2C19.
Subjects are admitted on Day -1 and stay for 2 periods of 4 days. Subjects are given a
single dose of omeprazole alone or with ASP8477 (in randomized order) on Day 1. Study
medication is administered under fasted conditions. Subjects are discharged on Day 3 and
return for an ESV 5-9 days later.
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Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science