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

NCT02243657 | Completed Phase 1

• 2 other identifiers: 3652-CL-00022008-006416-38
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Subjects; Pharmacokinetics of ASP3652; Pharmacodynamics of ASP3652

Keywords

ASP3652; Age; Gender; Pharmacokinetics; Pharmacodynamics; Phase 1; Multiple Ascending Doses (MAD)

Outcome Measures

Primary Outcomes (37)

• Nature, frequency and severity of adverse events

  Screening to 14 days after discharge

• Physical examination and vital signs

  Screening to 14 days after discharge

• Body temperature

  Screening to 14 days after discharge

• Routine safety laboratory tests

  Screening to 14 days after discharge

• 12 -lead Electrocardiogram (ECG)

  Screening to 14 days after discharge

• Holter ECG

  Day -1 and Day14

• Monitoring of psychotropic / cannabinoids-like effects

  Screening to 14 days after discharge

• Neurocognition Test Battery (NTB)

  Screening to 14 days after discharge

• Examination for skin lesions

  Screening to 14 days after discharge

• 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

• 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

• PK profile in plasma for first dose measured by maximum plasma concentration (Cmax)

  Day 1 to Day 2

• PK profile in plasma for first dose measured by time to attain Cmax (tmax)

  Day 1 to Day 2

• PK profile in plasma for first dose measured by elimination half-life (t½)

  Day 1 to Day 2

• PK profile in plasma for first dose measured by absorption lag time (tlag)

  Day 1 to Day 2

• PK profile in plasma for first dose measured by apparent volume of distribution during the terminal phase (Vz/F)

  Day 1 to Day 2

• 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

• 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

• 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

• 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

• 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

• PK profile in urine for first dose measured by renal clearance of the drug from plasma (CLR)

  Day 1 to Day 2

• 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

• 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

• PK profile in plasma for last dose measured by tmax

  Day 14 to Day 16

• PK profile in plasma for last dose measured by Cmax

  Day 14 to Day 16

• PK profile in plasma for last dose measured by t½

  Day 14 to Day 16

• PK profile in plasma for last dose measured by Vz/F

  Day 14 to Day 16

• PK profile in plasma for last dose measured by CL/F

  Day 14 to Day 16

• PK profile in plasma for last dose measured by accumulation ratio (Rac)

  Day 14 to Day 16

• PK profile in plasma for last dose measured by Peak Trough Ratio (PTR)

  Day 14 to Day 16

• 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

• 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

• 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

• PK profile in urine for last dose measured by CLR

  Only for BID dosing

  Day 14 to Day 16

• 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

• 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

Secondary Outcomes (5)

• Assessment of Pharmacodynamics measured by Ex vivo enzyme activity in mononuclear cells

  Day -1 to Day 16

• Pharmacodynamics measured by levels of arachidonoyl-ethanolamide (AEA) in plasma and seminal fluid (exploratory)

  Day -2 or -1 and day 11, 12 or 13

• Pharmacodynamics measured by levels of oleoyl-ethanolamide (OEA) in plasma and seminal fluid (exploratory)

  Day -2 or -1 and day 11, 12 or 13

• Pharmacodynamics measured by levels of palmitoyl-ethanolamide (PEA) in plasma and seminal fluid (exploratory)

  Day -2 or -1 and day 11, 12 or 13

• Assessment of Pharmacodynamics measured by intraocular pressure (IOP) (exploratory)

  Day -1 to Day 15

Study Arms (6)

1: Placebo dose level

PLACEBO COMPARATOR

Drug: Placebo

2: ASP3652 lowest dose level twice daily

EXPERIMENTAL

Drug: ASP3652

3:ASP3652 low dose level twice daily

EXPERIMENTAL

Drug: ASP3652

4: ASP3652 medium dose level twice daily

EXPERIMENTAL

Drug: ASP3652

5: ASP3652 high dose level twice daily

EXPERIMENTAL

Drug: ASP3652

6: ASP3652 highest dose level once daily

EXPERIMENTAL

Drug: ASP3652

Interventions

ASP3652 DRUG

oral

2: ASP3652 lowest dose level twice daily; 3:ASP3652 low dose level twice daily; 4: ASP3652 medium dose level twice daily; 5: ASP3652 high dose level twice daily; 6: ASP3652 highest dose level once daily

Placebo DRUG

oral

1: Placebo dose level

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

PRA International

Groningen, 9713GZ, Netherlands

Location

MeSH Terms

Conditions

Coitus

Interventions

ASP3652

Condition Hierarchy (Ancestors)

Sexual Behavior; Behavior

Study Officials

• Central Contact

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: September 18, 2014
• Study Start: May 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 18, 2014

Record last verified: 2014-09

Locations

NL (1)