Healthy Volunteers, Pharmacokinetics of Mirabegron
Conditions
Keywords
Pharmacokinetics, Cardiography, Impedance, Age groups, Gender Identity
Brief summary
Young and elderly, male and female subjects are each given 2 different doses of mirabegron for 7 days each. Levels of mirabegron in the blood are assessed.
Interventions
DRUGMirabegron
oral
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy elderly subject aged 55 years or more OR Healthy young subject aged 18 to 45 years, inclusive * Male must agree to sexual abstinence and/or use a highly effective method of birth control from screening until 3 months after last dose of study medication * Female subject must be of non-child bearing potential, i.e. post menopausal, surgically sterilized (e.g. tubal ligation), hysterectomy in medical history, or must practice an adequate non-hormonal contraceptive method to prevent pregnancies. Non-hormonal contraceptive methods are defined as: * Sexual abstinence from 1 month before admission until 3 months after discharge, OR * Subject's sexual partner has been surgically sterilized (since at least 3 months prior to the screening), OR * Subject is under two (2) of the following contraceptive methods: A) Diaphragm with spermicide; B)Intrauterine device; C)Sexual partner is using condoms in combination with a spermicidal creamDuring the study the subject is willing to use 1 of the 3 following contraceptive methods: diaphragm with spermicide, intrauterine device or partner is using condoms in combination with a spermicidal cream * Body Mass Index between 18.5 and 30.0 kg/m2, inclusive
Exclusion criteria
* Known or suspected hypersensitivity to Mirabegron or any components of the formulation used * Pregnant or breast feeding within 6 months before screening assessment * Any of the liver function tests (i.e. ALT, AST and Alkaline phosphatase) above the upper limit of normal at repeated measurements * Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active Hay-fever) * Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the investigator * Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests * A hemoglobin value \<13 g/dl (8.1 mmol/l) for males or \<12 g/dl (7.5 mmol/l) for females OR a hematocrit value \<40.0% for males or \<37% for females OR a Red Blood Cell count \<4.5 T/l (4500 mm3) for males or \<3.8 T/l (3800 mm3) for females at screening and/or on the day of admission into the clinical unit * Abnormal pulse and/or blood pressure measurements at the pre-study visit as follows: Pulse \<40 or \>90 bpm; mean systolic blood pressure \>160 mmHg (elderly) or \>140 mmHg (young); mean diastolic blood pressure \>100 mmHg (elderly) or \>90 mmHg (young), blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically * A marked baseline prolongation of QT/QTc interval after repeated measurements of \>450 ms, a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS) * Use of any prescribed or OTC (over-the-counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day) * Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit * Any use of drugs of abuse within 3 months prior to admission to the Clinical Unit * History of drinking more than 21 units of alcohol for males or more than 14 units of alcohol per week for females (1 unit = 270 cc of beer or 40 cc of spirits or 1 glass of wine) within 3 months prior to admission to the Clinical Unit * Positive test for drugs of abuse or positive alcohol test at screening and/or on the day of admission into the clinical unit * History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the Clinical Unit * Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study * Donation of blood or blood products within 3 months prior to admission to the Clinical Unit * Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2 * Subjects who, in the opinion of the investigator, are not likely to complete the trial for any reason * Any clinical condition, which, in the opinion of the investigator would not allow safe completion of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessment of pharmacokinetics of mirabegron and its metabolites | Days 6 - 14 + Days 21 - 29 |
Secondary
| Measure | Time frame |
|---|---|
| Impedance cardiography assessed through evaluation of cardiac outputs, stroke volume, systemic vascular resistance index, mean arterial blood pressure and heart rate | Days -1, 1, 6 and 7 |
Countries
France
Outcome results
None listed