Clinical trial NCT02010944: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Phase 1
Bioavailability
Healthy Subjects
Keywords: Solifenacin
Mirabegron
Fixed-dose combination (FDC)
Single Entity Tablet (SET)
Pharmacokinetics
Bioavailability
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2013-12-13
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic parameter of solifenacin in plasma as measured by Cmax (Maximum concentration)
timeFrame: Days 1-11
measure: Pharmacokinetic parameter of solifenacin in plasma as measured by AUClast (AUC until last sample taken)
timeFrame: Days 1-11
measure: Pharmacokinetic parameter of solifenacin in plasma as measured by AUCinf (AUC extrapolated until infinity)
timeFrame: Days 1-11
measure: Pharmacokinetic parameter of mirabegron in plasma as measured by Cmax (Maximum concentration)
timeFrame: Days 1-11
measure: Pharmacokinetic parameter of mirabegron in plasma as measured by AUClast (AUC until last sample taken)
timeFrame: Days 1-11
measure: Pharmacokinetic parameter of mirabegron in plasma as measured by AUCinf (AUC extrapolated until infinity)
timeFrame: Days 1-11
Secondary outcomes:
measure: Pharmacokinetic profile of Solifenacin in plasma
timeFrame: Days 1-11
measure: Pharmacokinetic profile of mirabegron in plasma
timeFrame: Days 1-11
measure: Safety and tolerability of solifenacin succinate and mirabegron assessed by adverse events, vital signs, laboratory tests, physical examination and 12-lead electrocardiogram (ECG)
timeFrame: Screening to End of Study Visit (Day 11 Period 3 or within 7 to 14 days after discontinuation)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Parexel
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Study Manager
role: STUDY_CHAIR
References: