A Study to Assess the Effect of Multiple Doses of Gemfribozil on a Single Dose of ASP3652, and to Assess the Effects of Multiple Doses of ASP3652 on a Single Dose of Repaglinide in the Body of Healthy Subjects

Sponsor

Astellas Pharma Europe B.V. (Industry)

Overall Status

Completed

CT.gov ID

NCT01797198

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

ASP3652 is being investigated as a novel treatment for chronic pelvic pain. This is a two-part study to investigate the drug-drug potential of ASP3652.

Part I of the study evaluates the effect of gemfibrozil twice daily on the single dose of ASP3652.

Part 2 evaluates the effect of multiple doses of ASP3652 twice daily on the single dose of repaglinide.

Subjects participating in one part of the study may not participate in the other part.

Condition or Disease	Intervention/Treatment	Phase
Drug-Drug Interaction (DDI) Healthy Subjects	Drug: ASP3652 Drug: Gemfibrozil Drug: Repaglinide	Phase 1

Detailed Description

Part 1:

On Day 1, a single dose of ASP3652 is administered. After a wash-out period of 3 days, bid (twice daily) dosing of gemfibrozil starts on Day 4 and continues for 7 days until Day 10. On Day 8 (the 5th day of gemfibrozil administration), a single dose of ASP3652 is administered one hour after the morning dose of gemfibrozil.

Part 2:

On Day 1, a single dose of repaglinide is administered. After a wash-out period of 3 days, bid dosing of ASP3652 starts on Day 4 and continues for 7 days until Day 10. On Day 8 (the 5th day of ASP3652 administration), a single dose of repaglinide is administered one hour after the morning dose of ASP3652.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

An Open Label, Drug-drug Interaction Study to Assess the Effect of Multiple Doses of Gemfibrozil on the Single Dose Pharmacokinetics of ASP3652 and to Assess the Effect of Multiple Doses of ASP3652 on the Single Dose Pharmacokinetics of Repaglinide

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: gemfibrozil + ASP3652 Multiple doses of gemfibrozil and single dose of ASP3652	Drug: ASP3652 Oral Drug: Gemfibrozil Oral
Experimental: ASP3652 + repaglinide Multiple doses of ASP3652 and the single dose of repaglinide	Drug: ASP3652 Oral Drug: Repaglinide Oral

Arm

Intervention/Treatment

Experimental: gemfibrozil + ASP3652

Multiple doses of gemfibrozil and single dose of ASP3652

Drug: ASP3652

Oral

Drug: Gemfibrozil

Oral

Experimental: ASP3652 + repaglinide

Multiple doses of ASP3652 and the single dose of repaglinide

Drug: ASP3652

Oral

Drug: Repaglinide

Oral

Outcome Measures

Primary Outcome Measures

Effect of multiple doses of gemfibrozil on the Pharmacokinetics (PK) of a single dose of ASP3652 (plasma) and metabolites H1/H2/H3 [Days 1 - 11]
Part 1: Maximum concentration (Cmax), AUClast and AUCinf
Effect of multiple doses of ASP3652 on the PK of a single dose of repaglinide and metabolite M4 (plasma) [Days 1 - 10]
Part 2: Cmax, AUClast, AUCinf, and the ratio AUC(M4) / AUC(repaglinide)
Assess the safety of single and multiple doses of ASP3652 alone and in combination with gemfibrozil or repaglinide [Screening - End of Study Visit (7-14 days after (early) discharge)]
Both Parts: Vital signs, physical examination, adverse events, electrocardiogram, clinical laboratory assessments, body temperature, Bond and Lader Visual Analogue Scale (VAS) questionnaire, Physician's Withdrawal Checklist (PWC)

Secondary Outcome Measures

Effect of multiple doses of gemfibrozil on the PK of a single dose of ASP3652 (plasma), metabolites H1/H2/H3 and Parent gemfibrozil and gemfibrozil-1-O-ß-glucuronide (plasma) [Days 1-11]
Part 1: tmax, tlag, t1/2, Vz/F, CL/F, Cmax, morning and evening Ctrough, tmax, AUCtau and CL/F
Effect of multiple doses of ASP3652 on the PK of a single dose of repaglinide [Days 1-10]
Part 2: tmax, tlag, t1/2, Vz/F, CL/F, Cmax, morning and evening Ctrough, tmax, AUCtau and CL/F
Effect of ASP3652 on the Pharmacodynamics (PD) of repaglinide by comparing the effect of repaglinide on blood glucose levels in the presence and absence of ASP3652 [Days 1-10]
Part 2: Baseline blood glucose concentration, minimum blood glucose concentration, and mean blood glucose concentration from 0 to 9h after dosing of repaglinide

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subject is white and of Caucasian origin.
Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m2.
Male subjects must agree to practice an effective contraceptive method with female sexual partners to prevent pregnancy.

Exclusion Criteria:

Known or suspected hypersensitivity to ASP3652, repaglinide and/or gemfibrozil, or any components of the formulation used.
Any of the liver function tests (ALT, AST, γ-GT, TBL and ALP) above the upper limit of normal. In such case the sample may be repeated once.
Regular use of any inducer of metabolism (e.g. barbiturates, Rifampicin) in the 3 months prior to admission to the Clinical Unit.