A Study to Evaluate Whether Verapamil Has an Effect on the Uptake and Elimination of Solifenacin and Tamsulosin When Administered in a Combination Tablet

Phase 1

Completed

• Conditions: Drug-Drug Interaction (DDI); Healthy Subjects
• Interventions: Drug: EC905; Drug: verapamil

• Registration Number: NCT01943487
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

This study investigates the effect of the co-administration of verapamil on the steady-state pharmacokinetics (PK) of solifenacin succinate and tamsulosin given as a combination tablet, EC905.

Detailed Description

The effect of the co-administration of verapamil on the steady state PK of solifenacin succinate and tamsulosin HCl OCAS (Oral Controlled Absorption System) is evaluated in this study.

Verapamil has been chosen to represent the effect of moderate CYP3A4 inhibitors on the combined administration of solifenacin and tamsulosin given as combination tablet EC905.

Subjects are admitted to the clinic on Day -1. From Days 1-10, they receive one daily dose of EC905 to obtain steady state, followed by 20 days (Days 11-30) combined dosing of EC905 and verapamil.

On Day 10 a 24-hour PK profile is obtained for solifenacin/tamsulosin. After the last dosing on Day 30, a post-dose 24-hour PK profile for solifenacin/tamsulosin and verapamil is obtained.

Additionally, vital signs, safety ECG (Electrocardiogram) measurements, safety laboratory assessments, adverse events and concomitant medications are monitored throughout the investigational period.

Subjects return for an ESV (End of Study Visit) 10 days after the last dosing.

Study Timeline

• Study Start: 2009-08
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Study First Submitted: 2013-09-12
• Study First Submitted QC: 2013-09-12
• Study First Posted: 2013-09-17
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-29
• Last Update Posted: 2014-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 36

Inclusion Criteria

• Body Mass Index between 18.5 and 30.0 kg/m2, inclusive

Exclusion Criteria

• Known or suspected hypersensitivity to EC905 or any of the components of the formulation used
• Known or suspected hypersensitivity to verapamil or any of the components of the formulation used
• Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1: verapamil + EC905	EC905	-
1: verapamil + EC905	verapamil	-

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of tamsulosin OCAS in plasma: AUCtau	Predose, Days 1, and 7-10	AUCtau (area under the plasma concentration-time curve during the time interval between consecutive dosing)
Pharmacokinetics of solifenacin in plasma: AUCtau	Predose, Days 1, and 7-10	AUCtau (area under the plasma concentration-time curve during the time interval between consecutive dosing)
Pharmacokinetics of tamsulosin OCAS in plasma: Cmax	Predose, Days 1, and 7-10	Cmax (maximum concentration)
Pharmacokinetics of solifenacin in plasma: Cmax	Predose, Days 1, and 7-10	Cmax (maximum concentration)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of combined doses of tamsulosin OCAS and solifenacin in steady state, and verapamil	Predose, Days 27-30	Plasma: Ctrough (trough concentration), tmax (time to attain Cmax), CL/F (apparent total body clearance), PTR (peak trough ratio) Urine: AUCtau, Cmax, Ctrough, CL/F, tmax
Safety and tolerability of the interaction between combined doses of tamsulosin OCAS and solifenacin, and verapamil	Screening to ESV (10 days after the last dosing)	AE (adverse events), clinical laboratory tests, vital signs, ECG, physical examination

Trial Locations

Locations (1)

SGS Aster; 🇫🇷 Paris, France