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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

Phase 1
Completed
Conditions
Drug-Drug Interaction (DDI)
Healthy Subjects
Interventions
Registration Number
NCT01797198
Lead Sponsor
Astellas Pharma Europe B.V.
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
48
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
gemfibrozil + ASP3652ASP3652Multiple doses of gemfibrozil and single dose of ASP3652
ASP3652 + repaglinideASP3652Multiple doses of ASP3652 and the single dose of repaglinide
gemfibrozil + ASP3652GemfibrozilMultiple doses of gemfibrozil and single dose of ASP3652
ASP3652 + repaglinideRepaglinideMultiple doses of ASP3652 and the single dose of repaglinide
Primary Outcome Measures
NameTimeMethod
Effect of multiple doses of gemfibrozil on the Pharmacokinetics (PK) of a single dose of ASP3652 (plasma) and metabolites H1/H2/H3Days 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 repaglinideScreening - 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
NameTimeMethod
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 repaglinideDays 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 ASP3652Days 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

Trial Locations

Locations (1)

PAREXEL Early Phase Clinical Unit

🇬🇧

Harrow, United Kingdom

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