Clinical trial NCT01489696: A Study to Evaluate Cardiovascular Interactions Between Mirabegron and Tamsulosin
Official title: A Study to Evaluate Cardiovascular Interactions Between Mirabegron and Tamsulosin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiovascular
Healthy Subjects
Pharmacokinetics
Keywords: Pharmacokinetics
Mirabegron
Tamsulosin
Phase 1
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-12-12
Enrollment: 48
Sex: MALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Cardiovascular interactions assessed by blood pressure and pulse rate
timeFrame: Pre-dose until 24 hours after dosing
Secondary outcomes:
measure: Monitoring of safety and tolerability through assessment of vital signs, ECG, clinical safety laboratory and adverse events
timeFrame: 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
measure: Potential PK interaction of the combination dosing assessed by serial plasma sampling
timeFrame: 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)
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance CRU Ltd
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_CHAIR
References: