A Study to Evaluate Cardiovascular Interactions Between Mirabegron and Tamsulosin

Phase 1

Completed

• Conditions: Healthy Subjects; Pharmacokinetics; Cardiovascular
• Interventions: Drug: mirabegron; Drug: tamsulosin

• Registration Number: NCT01489696
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

The study aims to compare blood pressure and pulse in male healthy subjects taking mirabegron and tamsulosin both alone and in combination.

Detailed Description

Treatment arm 1 (effect of mirabegron on tamsulosin): Subjects are randomized into one of two sequences.

Subjects receive 2 singles doses of tamsulosin, once in the absence of mirabegron and once in the presence of mirabegron.

24-hour Cardiovascular (CV) profiles are taken at both baseline days and after the single dose of tamsulosin /combination dose in each sequence. Regular blood samples are also taken to check for a potential Pharmacokinetic (PK) interaction.

Treatment arm 2 (effect of tamsulosin on mirabegron): Subjects are randomized into one of two sequences.

Subjects receive 2 singles doses of mirabegron, once in the absence of tamsulosin and once in the presence of tamsulosin.

24-hour CV profiles are taken at both baseline days and after the single dose of mirabegron/combination dose in each sequence. Regular blood samples are also taken to check for a potential PK interaction.

Study Timeline

• Study Start: 2010-08
• Primary Completion: 2011-02
• Study Completion: 2011-02
• Study First Submitted: 2011-11-21
• Status Verified: 2011-12
• Study First Submitted QC: 2011-12-08
• Study First Posted: 2011-12-12
• Last Update Submitted: 2013-12-06
• Last Update Posted: 2013-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 48

Inclusion Criteria

• Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m2

Exclusion Criteria

• Known or suspected hypersensitivity to mirabegron and/or tamsulosin HCl, or any components of the formulations used
• Any of the liver function tests (i.e. Alanine Aminotransferase (ALT) and Asparate Aminotransferase (AST) above the upper limit of normal at repeated measures (at least one more time)
• Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active hay fever)
• Any prior clinically significant psychiatric history including hospitalization for mental health management
• Subject is at risk of urinary retention based on medical history
• Any clinically significant abnormality following the investigator's review of the pre-study physical examination, Electrocardiogram (ECG) and clinical laboratory tests
• Heart rate and/or blood pressure measurements at the screening and admission visits as follows: Heart rate <50 or >90 bpm; mean systolic blood pressure <90 mm Hg or >140 mmHg (>160 mmHg for subjects 65 years or older); mean diastolic blood pressure <60 mm Hg or >90 mmHg (>100 mmHg for subjects 65 years or older) (blood pressure measurements to be taken after subject has been resting in supine position for 5 min; heart rate will be measured automatically; both to be taken in triplicate)
• A QTc interval of > 430 ms after repeated measurements (at least two more times), a history of syncope, orthostatic hypotension, vertigo, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS)
• A hemoglobin value <12.5 g/dl (7.8 mmol/l) and/or a hematocrit value <37.9% and/or a Red Blood Cell count <4.08 T/l (4080 mm3)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Arm 1	tamsulosin	tamsulosin singles doses; mirabegron multiple dose
Treatment Arm 2	mirabegron	mirabegron single doses; tamsulosin multiple dose
Treatment Arm 2	tamsulosin	mirabegron single doses; tamsulosin multiple dose
Treatment Arm 1	mirabegron	tamsulosin singles doses; mirabegron multiple dose

Primary Outcome Measures

Name	Time	Method
Cardiovascular interactions assessed by blood pressure and pulse rate	Pre-dose until 24 hours after dosing

Secondary Outcome Measures

Name	Time	Method
Potential PK interaction of the combination dosing assessed by serial plasma sampling	Arm 1: From time of combination dose until 4 days after combination dose (10 time points) / Arm 2: From time of combination dose until 8 days after combination dose (14 time points)
Monitoring of safety and tolerability through assessment of vital signs, ECG, clinical safety laboratory and adverse events	Arm 1: From time of combination dose until 4 days after combination dose / Arm 2: From time of combination dose until 8 days after combination dose

Trial Locations

Locations (1)

Covance CRU Ltd; 🇬🇧 Leeds, United Kingdom