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

Sponsor

Astellas Pharma Europe B.V. (Industry)

Overall Status

Completed

CT.gov ID

NCT01943487

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Drug-Drug Interaction (DDI) Healthy Subjects	Drug: EC905 Drug: verapamil	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Phase 1, Open-label, One-sequence Study to Assess the Effect of Verapamil on the Steady State Pharmacokinetics of Solifenacin and Tamsulosin Administered as a Combination Tablet EC905 in Healthy Male Subjects.

Study Start Date :

Aug 1, 2009

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1: verapamil + EC905	Drug: EC905 Oral Other Names: tamsulosin OCAS and solifenacin Drug: verapamil Oral

Arm

Intervention/Treatment

Experimental: 1: verapamil + EC905

Drug: EC905

Oral

Other Names:

tamsulosin OCAS and solifenacin

Drug: verapamil

Oral

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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