A Study to Assess the Safety, Tolerability, and Effects in and on the Body of Healthy Young and Elderly Male and Female Subjects of Ascending Multiple Oral Doses of ASP3652

Healthy Subjects Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Multiple Oral Doses of ASP3652 in Healthy Young and Elderly Male and Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02243657
• Other study ID #: 3652-CL-0002
• Secondary ID: 2008-006416-38
• Status: Completed
• Phase: Phase 1
• First received: August 19, 2014
• Last updated: September 16, 2014
• Start date: May 2009
• Est. completion date: May 2010

Study information

• Verified date: September 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: The Netherlands: The Central Committee on Research Involving Human Subjects
• Study type: Interventional

Clinical Trial Summary

The study investigates how safe ASP3652 is and how well it is tolerated when taken as multiple doses. The study also assesses how quickly and to what extent it is absorbed and eliminated from the body. In addition, the effects of age and gender are investigated.

The study consists of two parts. In Part 1 four dose levels are administered to four separate groups initially. Two additional dosages are then investigated. Subjects receive either a once-daily dose (QD) or twice-daily dose (BID) of ASP3652 or placebo.

Part 2 is performed in one group of elderly healthy male or female (post-menopausal) subjects. Subjects receive either a twice daily dose (BID) of ASP3652 or placebo.

For both parts of the study, the subjects stay in the clinic for one period of 18 days.

Description:

This is a Multiple Ascending Dose (MAD) study with two parts. Screening for both parts takes place between Days -28 and -3. Subjects are admitted to the clinic on Day -2, and discharged on Day 16. They return for an End of Study Visit (ESV) between 7 and 14 days after (early) discharge.

Part 1 evaluates the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ASP3652 following ascending multiple oral doses. The initially planned four dose levels or matching placebo are given to four separate groups. Thereafter two additional dosage levels are further investigated. All groups receive a single dose of ASP3652 administered in the morning of Day 1 and Day 14, and twice-daily doses administered from Day 2 to Day 13 under fasted conditions, except the last group which receives all dosages once daily from Day 1 to Day 14.

Part 2 evaluates the safety, tolerability, PK and PD of ASP3652 following ascending multiple oral doses in healthy elderly male and female subjects. This part contains a single, placebo-controlled group. All subjects receive twice daily doses and administration is based on the results of Part 1.

All subjects in both parts receive training for Neurocognitive Test Battery (NTB) and tests for monitoring of psychotropic effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Body Mass Index (BMI) between 18.5-30.0 kg/m2 for both male and female subjects.

• Male subject is non-fertile, i.e. surgically sterilized or practices an adequate contraceptive method to prevent pregnancies.

• Female subject is of non-child bearing potential, i.e. post menopausal, surgically sterilized, hysterectomy in medical history, or practices adequate (double barrier) non-hormonal contraceptive method to prevent pregnancies.

Exclusion Criteria:

• Pregnant or breast feeding within 6 months before screening assessment.

• Presence or history of any clinically significant psychiatric disorder such as mania, depression or schizophrenia.

• Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacodynamics of ASP3652
• Pharmacokinetics of ASP3652

Intervention

Drug:
• ASP3652
oral
• Placebo
oral

Locations

Country	Name	City	State
Netherlands	PRA International	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nature, frequency and severity of adverse events		Screening to 14 days after discharge	No
Primary	Physical examination and vital signs		Screening to 14 days after discharge	No
Primary	Body temperature		Screening to 14 days after discharge	No
Primary	Routine safety laboratory tests		Screening to 14 days after discharge	No
Primary	12 -lead Electrocardiogram (ECG)		Screening to 14 days after discharge	No
Primary	Holter ECG		Day -1 and Day14	No
Primary	Monitoring of psychotropic / cannabinoids-like effects		Screening to 14 days after discharge	No
Primary	Neurocognition Test Battery (NTB)		Screening to 14 days after discharge	No
Primary	Examination for skin lesions		Screening to 14 days after discharge	No
Primary	Pharmacokinetic (PK) profile in plasma for first dose measured by area under the plasma concentration - time curve from time zero to infinity (AUCinf)		Day 1 to Day 2	No
Primary	PK profile in plasma for first dose measured by area under the plasma concentration - time curve from time zero to time of last measurable concentration (AUClast)		Day 1 to Day 2	No
Primary	PK profile in plasma for first dose measured by maximum plasma concentration (Cmax)		Day 1 to Day 2	No
Primary	PK profile in plasma for first dose measured by time to attain Cmax (tmax)		Day 1 to Day 2	No
Primary	PK profile in plasma for first dose measured by elimination half-life (t½)		Day 1 to Day 2	No
Primary	PK profile in plasma for first dose measured by absorption lag time (tlag)		Day 1 to Day 2	No
Primary	PK profile in plasma for first dose measured by apparent volume of distribution during the terminal phase (Vz/F)		Day 1 to Day 2	No
Primary	PK profile in plasma for first dose measured by apparent total clearance of the drug from plasma after oral administration (CL/F)		Day 1 to Day 2	No
Primary	PK profile in urine for first dose measured by cumulative amount of unchanged drug excreted into the urine from time zero to time of last measurable concentration (Aelast)		Day 1 to Day 2	No
Primary	PK profile in urine for first dose measured by cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf)		Day 1 to Day 2	No
Primary	PK profile in urine for first dose measured by percentage of unchanged drug excreted into the urine from time zero to time of last measurable concentration (Aelast%)		Day 1 to Day 2	No
Primary	PK profile in urine for first dose measured by percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%)		Day 1 to Day 2	No
Primary	PK profile in urine for first dose measured by renal clearance of the drug from plasma (CLR)		Day 1 to Day 2	No
Primary	PK profile in plasma for last dose measured by area under the plasma concentration - time curve between consecutive dosing (AUCtau)	Only for Bis in die (twice daily) (BID) dosing	Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by area under the plasma concentration- time curve from the time of dosing up to 24 hours (AUC0-24)	Only for BID dosing	Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by tmax		Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by Cmax		Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by t½		Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by Vz/F		Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by CL/F		Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by accumulation ratio (Rac)		Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by Peak Trough Ratio (PTR)		Day 14 to Day 16	No
Primary	PK profile in plasma for last dose measured by plasma concentration at the end of a dosing interval at steady state (Ctrough)		Day 14 to Day 16	No
Primary	PK profile in urine for last dose measured by cumulative amount of drug excreted into urine over the time interval between consecutive dosing (Aetau)	Only for BID dosing	Day 14 to Day 16	No
Primary	PK profile in urine for last dose measured by fraction of the drug excreted into urine (Aetau) over the time interval between consecutive dosing (Aetau%)	Only for BID dosing	Day 14 to Day 16	No
Primary	PK profile in urine for last dose measured by CLR	Only for BID dosing	Day 14 to Day 16	No
Primary	PK profile in urine for last dose measured by cumulative amount of unchanged drug excreted into the urine from 0 to 24 hours (Ae0-24)	Only for BID dosing	Day 14 to Day 16	No
Primary	PK profile in urine for last dose measured by percentage of unchanged drug excreted into the urine from 0 to 24 hours (Ae0-24%)		Day 14 to Day 16	No
Secondary	Assessment of Pharmacodynamics measured by Ex vivo enzyme activity in mononuclear cells		Day -1 to Day 16	No
Secondary	Pharmacodynamics measured by levels of arachidonoyl-ethanolamide (AEA) in plasma and seminal fluid (exploratory)		Day -2 or -1 and day 11, 12 or 13	No
Secondary	Pharmacodynamics measured by levels of oleoyl-ethanolamide (OEA) in plasma and seminal fluid (exploratory)		Day -2 or -1 and day 11, 12 or 13	No
Secondary	Pharmacodynamics measured by levels of palmitoyl-ethanolamide (PEA) in plasma and seminal fluid (exploratory)		Day -2 or -1 and day 11, 12 or 13	No
Secondary	Assessment of Pharmacodynamics measured by intraocular pressure (IOP) (exploratory)		Day -1 to Day 15	No