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

NCT ID: NCT02220777

Last Updated: 2014-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2011-05-31

Brief 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.

Conditions

Pharmacokinetics of ASP8477; Pharmacodynamics of ASP8477

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

1. ASP8477 and placebo

Part 1: SAD in postmenopausal females and Part 2: SAD in vasectomized male

Group Type: EXPERIMENTAL

ASP8477

Intervention Type: DRUG

oral

Placebo

Intervention Type: DRUG

oral

2. ASP8477 alone

Part 3, fasted or fed

Group Type: EXPERIMENTAL

ASP8477

Intervention Type: DRUG

oral

3. omeprazole alone

Part 4, Drug-Drug Interaction

Group Type: EXPERIMENTAL

omeprazole

Intervention Type: DRUG

oral

4. ASP8477 + omeprazole

Part 4: Drug-Drug Interaction

Group Type: EXPERIMENTAL

ASP8477

Intervention Type: DRUG

oral

omeprazole

Intervention Type: DRUG

oral

Interventions

ASP8477

oral

Intervention Type: DRUG

omeprazole

oral

Intervention Type: DRUG

Placebo

oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy young (<65 years of age at first planned dose) postmenopausal female (Parts I, III, and IV).
• Healthy young vasectomized male subject aged 18-55 years inclusive (Part II).
• Body Mass index between 18.5 and 30.0 kg/m2 inclusive.

Exclusion Criteria

• Known or suspected hypersensitivity to ASP8477 or any of the components of the formulations used.
• Any of the liver function tests above the upper limit of normal.
• A family history of psychiatric disorders.
• Use of grapefruit (more than 3 x 200 ml) or marmalade (more than three times) in the week prior to admission to the Clinical Unit, as reported by the subject.
• Use of xanthine-containing beverages within 48 hours before admission.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Manager

Role: STUDY_CHAIR

Astellas Pharma Europe B.V.

Locations

SGS Belgium N.V.

Antwerp, , Belgium

SGS Aster

Paris, , France

Countries

Belgium; France

Other Identifiers

2009-017865-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8477-CL-0001

Identifier Type: -

Identifier Source: org_study_id