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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Drug-Drug Interaction (DDI)
• Intervention / Treatment: Drug: EC905; Drug: verapamil

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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • SGS Aster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of combined doses of tamsulosin OCAS and solifenacin in steady state, and verapamil	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	Predose, Days 27-30
Safety and tolerability of the interaction between combined doses of tamsulosin OCAS and solifenacin, and verapamil	AE (adverse events), clinical laboratory tests, vital signs, ECG, physical examination	Screening to ESV (10 days after the last dosing)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Publications and helpful links

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 12, 2013
• First Submitted That Met QC Criteria: September 12, 2013
• First Posted (Estimate): September 17, 2013

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase I; Verapamil; Solifenacin; Tamsulosin OCAS; EC905
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tamsulosin; Verapamil; Solifenacin Succinate
• Other Study ID Numbers: 905-CL-078; 2009-010841-29 (EudraCT Number)