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

Healthy Subjects Clinical Trial

Official title:

An Open-label, Parallel Group, Randomized, Two-sequence, Three-way Crossover Study to Assess the Relative Bioavailability of Solifenacin Succinate and Mirabegron Fixed-dose Combination Tablets Compared to Co-administration of Single Entity Tablets at Three Dose Strengths in Healthy Male and Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02010944
• Other study ID #: 178-CL-103
• Secondary ID: 2012-002650-23
• Status: Completed
• Phase: Phase 1
• First received: October 4, 2013
• Last updated: December 10, 2013
• Start date: September 2012
• Est. completion date: November 2012

Study information

• Verified date: October 2013
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bioavailability
• Healthy Subjects
• Phase 1

Intervention

Drug:
• solifenacin succinate
oral
• mirabegron
oral
• mirabegron/solifenacin succinate
oral

Locations

Country	Name	City	State
Germany	Parexel	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameter of solifenacin in plasma as measured by Cmax (Maximum concentration)		Days 1-11	No
Primary	Pharmacokinetic parameter of solifenacin in plasma as measured by AUClast (AUC until last sample taken)		Days 1-11	No
Primary	Pharmacokinetic parameter of solifenacin in plasma as measured by AUCinf (AUC extrapolated until infinity)		Days 1-11	No
Primary	Pharmacokinetic parameter of mirabegron in plasma as measured by Cmax (Maximum concentration)		Days 1-11	No
Primary	Pharmacokinetic parameter of mirabegron in plasma as measured by AUClast (AUC until last sample taken)		Days 1-11	No
Primary	Pharmacokinetic parameter of mirabegron in plasma as measured by AUCinf (AUC extrapolated until infinity)		Days 1-11	No
Secondary	Pharmacokinetic profile of Solifenacin in plasma	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)	Days 1-11	No
Secondary	Pharmacokinetic profile of mirabegron in plasma	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)	Days 1-11	No
Secondary	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)	No