Drug-Drug Interaction (DDI), Healthy Subjects
Conditions
Keywords
Phase I, ASP3652, Gemfibrozil, Repaglinide, Pharmacokinetics
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.
Interventions
Sponsors
Astellas Pharma Europe B.V.
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United Kingdom
Outcome results
None listed