Study to Evaluate the Effect of Solifenacin and Mirabegron on the Digoxin Concentrations in Blood in Healthy Subjects

Exclusion Criteria

• •Female subject who has been pregnant within 6 months prior to screening assessment or breast feeding within 3 months prior to screening.
• •Subject has a known or suspected hypersensitivity to solifenacin succinate, mirabegron, digoxin or any components of the formulations used.
• •Subject has any of the liver function tests (LFTs) (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], GGT, total bilirubin \[TBL\]) above the upper limit of normal (ULN). In such a case the assessment may be repeated once \[day -1\].
• •Subject has any clinically significant history of allergic conditions.
• •Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to day -1.
• •Subject has any clinically significant abnormality following the Investigator's review of the physical examination, ECG (e.g., any level of sinus node disease or atrioventricular defect) and protocol defined clinical laboratory tests (e.g., electrolyte abnormalities such as hypokalemia) at screening or day -1.
• •Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the medical Investigator.
• •Subject has a mean heart rate (HR) of \< 50 or \> 90 beats per minute (bpm); mean systolic BP \>140 mmHg; mean diastolic BP \> 90 mmHg at day-1 (vital sign measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically).
• •Subject has a mean QTc(F) interval of \> 430 ms (for males) and \> 450 ms (for females) at day-1. If the mean QTc(F) exceeds the limits above, 1 additional triplicate ECG can be taken. If this triplicate also gives abnormal result the subject should be excluded.
• •Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease, or a family history of Long QT Syndrome.
• •Subject has any clinically significant history of or risk of urinary retention, severe gastrointestinal condition (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma.
• •Subject uses any prescribed or non-prescribed drugs (including vitamins, hormone replacement therapy or natural and herbal remedies \[e.g., St. John's Wort\]) in the 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g/day).
• •Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit.
• •Subject has a history of drinking more than 21 units (14 units for females) of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer \[5\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) within 3 months prior to admission to the clinical unit.
• •Subject consumes grapefruit juice (more than 3 x 200 mL) or marmalade (more than 3 times) star fruit, Seville oranges or Seville orange juice containing products in the week prior to admission to the clinical unit until end of study visit (ESV), as reported by the subject.
• •Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit.
• •Subject regularly uses of any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the clinical unit.
• •Subject has significant blood loss, donated 1 unit (500 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on day -1.
• •Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibodies, hepatitis A virus (HAV) antibodies (Immunoglobulin M \[IgM\]), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) 1+2 antibodies.
• •Subject participated in any clinical study or has been treated with any investigational drugs within 28 days prior to screening.
• •Subject is a vulnerable subject (e.g., subject kept in detention).
• •Subject is an employee of the Astellas Group or Contract Research Organization (CRO) involved in the clinical study.