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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Drug-Drug Interaction (DDI)
• Intervention / Treatment: Drug: Gemfibrozil; Drug: ASP3652; Drug: Repaglinide

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3U
    • PAREXEL Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of multiple doses of gemfibrozil on the Pharmacokinetics (PK) of a single dose of ASP3652 (plasma) and metabolites H1/H2/H3	Part 1: Maximum concentration (Cmax), AUClast and AUCinf	Days 1 - 11
Effect of multiple doses of ASP3652 on the PK of a single dose of repaglinide and metabolite M4 (plasma)	Part 2: Cmax, AUClast, AUCinf, and the ratio AUC(M4) / AUC(repaglinide)	Days 1 - 10
Assess the safety of single and multiple doses of ASP3652 alone and in combination with gemfibrozil or repaglinide	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)	Screening - End of Study Visit (7-14 days after (early) discharge)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Part 1: tmax, tlag, t1/2, Vz/F, CL/F, Cmax, morning and evening Ctrough, tmax, AUCtau and CL/F	Days 1-11
Effect of multiple doses of ASP3652 on the PK of a single dose of repaglinide	Part 2: tmax, tlag, t1/2, Vz/F, CL/F, Cmax, morning and evening Ctrough, tmax, AUCtau and CL/F	Days 1-10
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	Part 2: Baseline blood glucose concentration, minimum blood glucose concentration, and mean blood glucose concentration from 0 to 9h after dosing of repaglinide	Days 1-10

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: February 20, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (ESTIMATE): February 22, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): February 22, 2013
• Last Update Submitted That Met QC Criteria: February 20, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase I; Gemfibrozil; ASP3652; Repaglinide
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP2C8 Inhibitors; Gemfibrozil; Repaglinide
• Other Study ID Numbers: 3652-CL-0006; 2011-002874-21 (EUDRACT_NUMBER)