A Study to Evaluate Cardiovascular Interactions Between Mirabegron and Tamsulosin

• Monitoring of safety and tolerability through assessment of vital signs, ECG, clinical safety laboratory and adverse events [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
• Potential PK interaction of the combination dosing assessed by serial plasma sampling [ Time Frame: 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) ] [ Designated as safety issue: No ]

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

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.

• Cardiovascular
• Healthy Subjects
• Pharmacokinetics

• Drug: mirabegron
  oral
  Other Name: YM178
• Drug: tamsulosin
  oral
  Other Names:

  • Flomax
  • Harnal
  • Omnic

• Experimental: Treatment Arm 1
  tamsulosin singles doses; mirabegron multiple dose
  Interventions:

  • Drug: mirabegron
  • Drug: tamsulosin
• Experimental: Treatment Arm 2
  mirabegron single doses; tamsulosin multiple dose
  Interventions:

  • Drug: mirabegron
  • Drug: tamsulosin

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)