Drug-Drug Interaction (DDI), Healthy Subjects
Conditions
Keywords
Phase I, Verapamil, Tamsulosin OCAS, Solifenacin, Pharmacokinetics, EC905
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.
Interventions
DRUGEC905
Oral
DRUGverapamil
Oral
Sponsors
Astellas Pharma Europe B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France
Outcome results
None listed