Cardiovascular, Healthy Subjects, Pharmacokinetics
Conditions
Keywords
Pharmacokinetics, Mirabegron, Tamsulosin, Phase 1
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.
Interventions
DRUGmirabegron
oral
DRUGtamsulosin
oral
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cardiovascular interactions assessed by blood pressure and pulse rate | Pre-dose until 24 hours after dosing |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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) |
Countries
United Kingdom
Outcome results
None listed