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

An Open-label, Randomized, 2-way Crossover Study to Evaluate the Pharmacokinetics of Mirabegron and Its Metabolites in Healthy Young and Elderly Male and Female Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of Mirabegron
• Intervention / Treatment: Drug: Mirabegron

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of pharmacokinetics of mirabegron and its metabolites	Days 6 - 14 + Days 21 - 29

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• Krauwinkel W, van Dijk J, Schaddelee M, Eltink C, Meijer J, Strabach G, van Marle S, Kerbusch V, van Gelderen M. Pharmacokinetic properties of mirabegron, a beta3-adrenoceptor agonist: results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women. Clin Ther. 2012 Oct;34(10):2144-60. doi: 10.1016/j.clinthera.2012.09.010.

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 27, 2011
• First Posted (Estimate): January 28, 2011

Study Record Updates

• Last Update Posted (Estimate): July 3, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Impedance; Age groups; Cardiography; Gender Identity
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron
• Other Study ID Numbers: 178-CL-072; 2008-006005-16 (EudraCT Number)