A Study to Compare How Much Solifenacin Succinate and Mirabegron Reach the Blood When Administered Together as Fixed-dose Combination Tablets and With Single Individual Tablets of the Same Medications at Three Dose Levels

Phase 1

Completed

• Conditions: Phase 1; Bioavailability; Healthy Subjects
• Interventions: Drug: solifenacin succinate; Drug: mirabegron; Drug: mirabegron/solifenacin succinate

• Registration Number: NCT02010944
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

This study compares the pharmacokinetics (PK), safety and tolerability of fixed dose combination (FDC) tablets containing solifenacin succinate and mirabegron with the co-administration of single entity tablets (SET), at three dose strengths.

Detailed Description

There are three parallel groups each with 24 healthy male and female subjects (with a minimum of 10 subjects per gender). Each group receives one dose strength.

The study utilizes a partial replicate cross-over design with three periods and each subject receives the same strength of either the FDC or SET formulation twice.

Screening takes place within 21 days before admission and subjects are admitted on Day -1. Dosing takes place on Day 1, after an overnight fast of at least 10 hours. Subjects remain fasted until 4 hours post-dose. There is a wash-out period of at least 14 days between each dose administration.

Subjects are discharged on Day 4 and return to the clinical unit on Days 5, 6, 7, 9 and 11 for outpatient assessments.

An End-of-Study Visit (ESV) takes place on Day 11 of Period 3 or within 7-14 days after discontinuation.

Study Timeline

• Study Start: 2012-09
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2013-10
• Study First Submitted: 2013-10-04
• Study First Submitted QC: 2013-12-10
• Last Update Submitted: 2013-12-10
• Study First Posted: 2013-12-13
• Last Update Posted: 2013-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

• Male subject must agree to not donate semen from the day of first dosing until 3 months after last discharge and practice an effective contraceptive method with female sexual partners to prevent pregnancy.
• Female subject must be of non-child bearing potential, i.e. postmenopausal, surgically sterilized, hysterectomy in medical history, or practicing highly effective non-hormonal birth control.

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 solifenacin succinate, mirabegron or any components of the formulations 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.
• Any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1: FDC-SET-SET	mirabegron/solifenacin succinate	Fixed Dose Combination followed by two periods of the Single Entity Tablets
2: SET-FDC-FDC	mirabegron	Single Entity Tablets followed by two periods of Fixed Dose Combination
2: SET-FDC-FDC	mirabegron/solifenacin succinate	Single Entity Tablets followed by two periods of Fixed Dose Combination
1: FDC-SET-SET	solifenacin succinate	Fixed Dose Combination followed by two periods of the Single Entity Tablets
1: FDC-SET-SET	mirabegron	Fixed Dose Combination followed by two periods of the Single Entity Tablets
2: SET-FDC-FDC	solifenacin succinate	Single Entity Tablets followed by two periods of Fixed Dose Combination

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic parameter of solifenacin in plasma as measured by AUCinf (AUC extrapolated until infinity)	Days 1-11
Pharmacokinetic parameter of solifenacin in plasma as measured by AUClast (AUC until last sample taken)	Days 1-11
Pharmacokinetic parameter of mirabegron in plasma as measured by Cmax (Maximum concentration)	Days 1-11
Pharmacokinetic parameter of solifenacin in plasma as measured by Cmax (Maximum concentration)	Days 1-11
Pharmacokinetic parameter of mirabegron in plasma as measured by AUClast (AUC until last sample taken)	Days 1-11
Pharmacokinetic parameter of mirabegron in plasma as measured by AUCinf (AUC extrapolated until infinity)	Days 1-11

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic profile of Solifenacin in plasma	Days 1-11	AUC0-72h (Area under the plasma concentration-time curve from time zero to 72h), tmax (Time to attain Cmax), tlag (Absorption lag time), t1/2 (Apparent terminal elimination half-life), Vz/F (Apparent volume of distribution), CL/F (Apparent total body plasma clearance)
Pharmacokinetic profile of mirabegron in plasma	Days 1-11	AUC0-72h (Area under the plasma concentration-time curve from time zero to 72h), tmax (Time to attain Cmax), tlag (Absorption lag time), t1/2 (Apparent terminal elimination half-life), Vz/F (Apparent volume of distribution), CL/F (Apparent total body plasma clearance)
Safety and tolerability of solifenacin succinate and mirabegron assessed by adverse events, vital signs, laboratory tests, physical examination and 12-lead electrocardiogram (ECG)	Screening to End of Study Visit (Day 11 Period 3 or within 7 to 14 days after discontinuation)

Trial Locations

Locations (1)

Parexel; 🇩🇪 Berlin, Germany