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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Drug-Drug Interaction (DDI), Healthy Subjects

Intervention / Treatment
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* Drug: EC905
* Drug: verapamil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: verapamil + EC905<br> | Drug: EC905<br>* Oral<br>* Other names: tamsulosin OCAS and solifenacin;Drug: verapamil<br>* Oral<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Verapamil, Tamsulosin OCAS, Solifenacin, Pharmacokinetics, EC905