A Study to Assess the Effects of Single Ascending Doses (SAD) of ASP8477, the Effect That Food Has on the Drug, and the Interaction Between ASP8477 and Omeprazole in Healthy Postmenopausal Females and Healthy Young Vasectomized Males
Condition: Pharmacokinetics of ASP8477; Pharmacodynamics of ASP8477
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): ASP8477; omeprazole; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): oral; oral; oral
Intervention MeSH terms: Omeprazole; ASP8477
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: MTD (Maximum Tolerated Dose); Food effect; Postmenopausal subjects; Vasectomized subjects; FIH (First In Humans); SAD (Single Ascending Dose); DDI (Drug-Drug Interaction)