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.
| Status | Completed |
| Enrollment | 72 |
| Est. completion date | May 2011 |
| Est. primary completion date | May 2011 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years to 65 Years |
| Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| Belgium | SGS Belgium N.V. | Antwerp | |
| France | SGS Aster | Paris |
| Lead Sponsor | Collaborator |
|---|---|
| Astellas Pharma Europe B.V. |
Belgium, France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | No |
| Primary | The assessment of pharmacokinetic parameter of ASP8477 measured by Maximum concentration (Cmax), in plasma | Maximum concentration (Cmax) | Day 1 to Day 3 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | The assessment of pharmacokinetic parameter of ASP8477 measured by Absorption lag time (tlag) in plasma | Absorption lag time (tlag) | Day 1 to Day 3 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | The assessment of pharmacokinetic parameter of ASP8477 measured by Renal clearance (CLR) in urine | Renal clearance (CLR) | Day 1 to Day 3 | No |
| Secondary | The assessment of pharmacokinetics of omeprazole measured by plasma concentration | Cmax, tmax, AUCinf, AUClast, t1/2, Vz/F, CL/F | Day 1 to Day 3 | No |
| Secondary | The assessment of pharmacodynamics of ASP8477 measured by serum concentration | serum concentration of endogenous substrates, volume of urine production, GFR and intra-ocular pressure | Day 1 to Day 4 | No |