A Study to Evaluate How Mirabegron Enters and Leaves the Bloodstream According to Age and Sex

Phase 1

Completed

• Conditions: Healthy Volunteers; Pharmacokinetics of Mirabegron

• Registration Number: NCT01285596
• Lead Sponsor: Astellas Pharma Inc

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03
• Primary Completion: 2009-11
• Study Completion: 2009-11
• Study First Submitted: 2011-01-18
• Study First Submitted QC: 2011-01-27
• Study First Posted: 2011-01-28
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-01
• Last Update Posted: 2013-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Assessment of pharmacokinetics of mirabegron and its metabolites	Days 6 - 14 + Days 21 - 29

Secondary Outcome Measures

Name	Time	Method
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