A Study to Investigate the Effect of Food With Mirabegron in Healthy Chinese Participants

An open-label, randomized, 2-period, single oral dose crossover design at 2 dose levels in healthy Chinese male and female participants. Each participant took part in 2 periods separated by a washout of at least 10 days between investigational product (IP) administrations in each period.

Participants were screened for up to 21 days prior to IP administration on day 1 of period 1. Eligible participants were admitted to the clinical unit on day -1 of each period and were confined until the last pharmacokinetic sample had been drawn within each period. PK samples were collected predose on day 1 of each period and at multiple time points following each dose.

Inclusion criteria

• Subject has a body mass index range of 19.0 to 24.9 kg/m^2, inclusive and weighs at least 50 kg for male subjects and 45 kg for female subjects at screening.
• Female subject is not pregnant and at least 1 of the following conditions apply:

• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final IP administration
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
• Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.
• Male subject with female partner(s) of childbearing potential (including breastfeeding partner[s]) must agree to use contraception throughout the study period and for 30 days after final IP administration.
• Male subject must not donate sperm during the study period and for 30 days after final IP administration.
• Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration.
• Subject agrees not to participate in another interventional study while participating in the present study, defined as 84 days prior screening until completion of the last study visit.

Exclusion criteria

• Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to mirabegron or any components of the formulation used.
• Subject has had previous exposure with mirabegron.
• Subject has any of the liver function tests (alkaline phosphatase, alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase and total bilirubin [TBL]) ≥ 1.5 × upper limit of normal (ULN) on day -1 of period 1.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to first IP administration.
• 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.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1 of period 1.
• Subject has any of the following concerns with regard to tuberculosis:

• History of active tuberculosis
• Abnormalities detected in a chest X-ray on day -1 of period 1
• Contact with infectious tuberculous patients
• Subject has any clinically significant abnormality following the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1 of period 1.
• Participant has a mean pulse < 45 bpm, > 99 bpm; mean body temperature < 35.0°C, > 37.5°C; mean systolic blood pressure < 90 mmHg, ≥ 140 mmHg; mean diastolic blood pressure < 40 mmHg, ≥ 90 mmHg (measurements taken in triplicate after participant has been resting in the supine position for at least 5 minutes) at screening or on day-1 of period 1. If the mean blood pressure exceeds the limits above, 1 additional triplicate may be taken.
• Participant has a mean corrected QT interval using Fridericia's formula (QTcF) of: ≥ 430 msec (for male subjects) ≥ 450 msec (for female subjects) at screening or on day-1 of period 1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG may be taken.
• Subject has used any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort and traditional Chinese medicine) in the 2 weeks prior to first IP administration, except for occasional use of paracetamol (up to 2 g/day), topical dermatological products, including corticosteroid products, hormonal contraceptives or hormone replacement therapy (HRT).
• Subject has a history of smoking > 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to day -1 of period 1.
• Subject has a history of consuming > 21 units for male subjects or > 14 units for female subjects of alcohol per week within 3 months prior to day -1 of period 1 (note: 1 unit = 10 g pure alcohol, 250 mL of beer [5%], 35 mL of spirits [35%] or 100 mL of wine [12%]) or the subject has a history of alcohol-dependency, drug-dependency, chemical-dependency, or alcohol or drug abuse within 2 years prior to screening or the subject tests positive for alcohol at screening or on day -1 of period 1.
• Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) within 3 months prior to day -1 of period 1 or the subject tests positive for drugs of abuse (amphetamines, benzodiazepines, cannabinoids, cocaine and opiates) at screening or on day -1 of period 1.
• Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1 of period 1.
• Subject has had significant blood loss, donated ≥ 400 mL of whole blood within 90 days, ≥ 200 mL of whole blood within 30 days or donated blood components within 14 days prior to day -1 of period 1 and/or received a transfusion of any blood or blood products within 60 days.
• Subject has a positive serology test for hepatitis A virus antibodies (immunoglobulin M), hepatitis B core antibodies, hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus or syphilis at screening.
• Subject is an employee of Astellas, the study-related contract research organizations or the clinical unit.