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

NCT02220777 | Completed Phase 1

• 2 other identifiers: 8477-CL-00012009-017865-42
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 2

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.

Conditions

Pharmacokinetics of ASP8477; Pharmacodynamics of ASP8477

Keywords

MTD (Maximum Tolerated Dose); Food effect; Postmenopausal subjects; Vasectomized subjects; FIH (First In Humans); SAD (Single Ascending Dose); DDI (Drug-Drug Interaction)

Outcome Measures

Primary Outcomes (14)

• Safety as assessed by recording adverse events, physical examination, laboratory assessments, vital signs, electrocardiograms (ECGs), cortisol levels, arterial carbon dioxide and oxygen saturation

  For Part I and II Bond-Lader Visual Analogue Scale (VAS) and Bowdle VAS assessments will also be taken.

  Day1 to End of Study Visit (5-9 days after final discharge)

• The assessment of pharmacokinetic parameter of ASP8477 measured by Maximum concentration (Cmax), in plasma

  Maximum concentration (Cmax)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Time to attain Cmax (tmax) in plasma

  Time to attain Cmax (tmax)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Area Under the Curve (AUC) extrapolated until infinity (AUCinf) in plasma

  Area Under the Curve (AUC) extrapolated until infinity (AUCinf)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by AUC until last sample taken (AUClast) in plasma

  AUC until last sample taken (AUClast), Absorption lag time (tlag), Apparent terminal elimination half-life (t1/2), Apparent volume of distribution (Vz/F), Apparent total body plasma clearance (CL/F)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Absorption lag time (tlag) in plasma

  Absorption lag time (tlag)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent terminal elimination half-life (t1/2) in plasma

  Apparent terminal elimination half-life (t1/2)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent volume of distribution (Vz/F) in plasma

  Apparent volume of distribution (Vz/F)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent total body plasma clearance (CL/F) in plasma

  Apparent total body plasma clearance (CL/F)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Amount excreted in urine until last sample (Aelast) in urine

  Amount excreted in urine until last sample (Aelast)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf) in urine

  Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%) in urine

  Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%) in urine

  Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%)

  Day 1 to Day 3

• The assessment of pharmacokinetic parameter of ASP8477 measured by Renal clearance (CLR) in urine

  Renal clearance (CLR)

  Day 1 to Day 3

Secondary Outcomes (2)

• The assessment of pharmacokinetics of omeprazole measured by plasma concentration

  Day 1 to Day 3

• The assessment of pharmacodynamics of ASP8477 measured by serum concentration

  Day 1 to Day 4

Study Arms (4)

1. ASP8477 and placebo

EXPERIMENTAL

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

Drug: ASP8477; Drug: Placebo

2. ASP8477 alone

EXPERIMENTAL

Part 3, fasted or fed

Drug: ASP8477

3. omeprazole alone

EXPERIMENTAL

Part 4, Drug-Drug Interaction

Drug: omeprazole

4. ASP8477 + omeprazole

EXPERIMENTAL

Part 4: Drug-Drug Interaction

Drug: ASP8477; Drug: omeprazole

Interventions

ASP8477 DRUG

oral

1. ASP8477 and placebo; 2. ASP8477 alone; 4. ASP8477 + omeprazole

omeprazole DRUG

oral

3. omeprazole alone; 4. ASP8477 + omeprazole

Placebo DRUG

oral

1. ASP8477 and placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (2)

SGS Belgium N.V.

Antwerp, B-2060, Belgium

Location

SGS Aster

Paris, 75015, France

Location

MeSH Terms

Conditions

Metatropic dwarfism

Interventions

ASP8477; Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Study Manager

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2014
• First Posted: August 20, 2014
• Study Start: November 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: August 20, 2014

Record last verified: 2014-08

Locations

FR (1); BE (1)