A Phase 4 Open-label, Randomized, Single Oral Dose, Two-way Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of Mirabegron in Healthy Chinese Subjects
A Phase 4 Open-label, Randomized, Single Oral Dose, Two-way Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of Mirabegron in Healthy Chinese Subjects
This study determined the effect of food on the pharmacokinetics (PK) of single oral doses of mirabegron in healthy Chinese male and female participants.
This study also evaluated the safety and tolerability of single oral doses of mirabegron in healthy Chinese male and female 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:
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:
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.