A Study to Assess the Effect of Race on How a Single Dose of ASP3652 is Taken up, Metabolized and Distributed Through the Bodies of Young, Healthy Male and Female Subjects, and Its Safety and Tolerability

A Phase 1 Open-label Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of a Single Dose of ASP3652 in Caucasian, Japanese, Black/African and Chinese Healthy Male and Female Subjects

This study investigates how ASP3652 is taken up, broken down, and distributed through the body and excreted in individuals of different races. The study also investigates levels of biochemical markers in the bloodstream, and determines how safe the study drug is and how well it is tolerated after dosing. A further aim is to look at how the processes of metabolism, distribution and excretion of the study drug are possibly altered by the daily diet of the volunteers taking part.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics; Pharmacodynamics; Effect of Race
• Intervention / Treatment: Drug: ASP3652

Detailed Description

This is an open label study to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of a single dose of ASP3652 in healthy male and female subjects from Caucasian, Japanese, Black/African and Chinese origin.

A total of 64 healthy male and female subjects are included in this study (16 subjects per race group). Each race group comprises 8 female subjects and 8 male subjects.

Screening assessments are performed from Day -22 to Day -2, and subjects are admitted to the clinic on Day -1, where they remain until Day 4. On Day 1, the subjects receive a single oral dose of ASP3652, and are discharged on Day 4 when all assessments have been performed and if there are no medical reasons to stay longer. An end of study visit (ESV) is performed 7-14 days after discharge.

For each race group, plasma samples for PK and PD analysis are collected. Vital signs, safety electrocardiogram (ECG) measurements, safety laboratory assessments, physical examination, adverse events (AEs) and concomitant medications are monitored throughout study.

In order to identify potential relationships between dietary intake and the PK of a single dose of ASP3652, all subjects record their diet for 3 days during the screening period in order to assess daily dietary intake (including total daily caloric intake; daily cholesterol intake; and total fat, saturated fat, carbohydrate and protein as a percentage of total calories).

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, H1 3UJ
    • PAREXEL Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subject is a healthy male or female subject from Caucasian, Japanese, Black/African or Chinese origin. Both parents and all 4 grandparents should be of the same race.
• Subjects of Japanese or Chinese origin should be born in their respective countries and should not have lived outside of their countries for more than 5 years and 10 years, respectively.
• The subject has a Body Mass Index (BMI) in the range 18.5 - 30.0 kg/m2, inclusive (subject from Caucasian or Black/African origin) or in the range 17.5 - 29.0 kg/m2, inclusive (subject from Japanese or Chinese origin). The subject weighs at least 50 kg (subject from Caucasian or Black/African origin) or at least 45 kg (subject from Japanese or Chinese origin).

Exclusion Criteria:

• Female subject who is pregnant, has been pregnant within 6 months before screening, or breast feeding within 3 months before screening.
• Known or suspected hypersensitivity to ASP3652 or any components of the formulation used.
• The subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to admission to the Clinical Unit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ASP3652; One single dose	Drug: ASP3652; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of ASP3652 in plasma measured by Cmax	maximum observed plasma concentration (Cmax)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by AUClast	area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by AUCinf	area under the plasma concentration-time curve from time zero extrapolated to the infinite time (AUCinf)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by tmax	time to attain Cmax (tmax)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by tlag	PK lag time (tlag)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by t1/2	apparent terminal elimination half-life (t1/2)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by Vz/F	apparent volume of terminal phase distribution at steady state (Vz/F)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by CL/F	apparent clearance after oral administration at steady state (CL/F)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by Vz/F/kg	body weight-adjusted apparent volume of terminal phase distribution at steady state (Vz/F/kg)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 in plasma measured by CL/F/kg	body weight-adjusted apparent clearance after oral administration at steady state (CL/F/kg)	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 metabolites in plasma measured by Cmax		Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 metabolites in plasma measured by AUClast		Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 metabolites in plasma measured by AUCinf		Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 metabolites in plasma measured by tmax		Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 metabolites in plasma measured by tlag	tlag	Day 1 to Day 4 (16 blood samples taken)
Pharmacokinetics of ASP3652 metabolites in plasma measured by t1/2		Day 1 to Day 4 (16 blood samples taken)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of arachidonoyl-ethanolamide (AEA, or anandamide), oleoyl-ethanolamide (OEA) and palmitoyl-ethanolamide (PEA) after a single dose of ASP3652	maximum response (Rmax), time of the maximum response (tmax R), area under the response curve (AUR)	Day 1 to Day 4 (12 blood samples taken)
Safety and tolerability of a single dose of ASP3652	vital signs, safety electrocardiogram measurements, safety laboratory assessments, physical examination and adverse events (AEs)	Screening to ESV (at least 39 safety assessments)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: October 4, 2013
• First Submitted That Met QC Criteria: October 4, 2013
• First Posted (ESTIMATE): October 8, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 8, 2013
• Last Update Submitted That Met QC Criteria: October 4, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Phase I; Single dose; Dietary intake; ASP3652
• Other Study ID Numbers: 3652-CL-0054; 2012-001476-11 (EUDRACT_NUMBER)