A Study in Healthy Young Men to Look at What Drives the Cardiovascular Effects After Dosing With Mirabegron.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01284868
Recruitment Status : Completed
First Posted : January 27, 2011
Last Update Posted : July 3, 2013
Information provided by:
Astellas Pharma Inc

Brief Summary:
To explore what is driving heart-rate increases after dosing with mirabegron. Subjects will be given a beta-blocker at the same time as mirabegron.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Pharmacodynamics of Mirabegron Drug: mirabegron Drug: Bisoprolol Drug: propranolol Drug: placebo Phase 1

Detailed Description:
Impedance cardiography parameters will be assessed and compared when mirabegron (or placebo), is taken in combination with a selective beta-blocker, a non-selective beta-blocker or placebo.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: An Exploratory Study Into the Mechanism of Mirabegron-induced Cardiovascular Effects in Healthy Male Subjects.
Study Start Date : July 2009
Actual Primary Completion Date : November 2009
Actual Study Completion Date : November 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Mirabegron
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Mirabegron Drug: mirabegron
Other Name: YM178
Drug: Bisoprolol
Drug: propranolol
Drug: placebo

Primary Outcome Measures :
  1. Plasma renin activity [ Time Frame: 12 hours ]
  2. Impedance cardiography [ Time Frame: 12 hours ]

Secondary Outcome Measures :
  1. Pharmacokinetic assessment of mirabegron by analysis of plasma samples [ Time Frame: 12 hours ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Body Mass Index between 20.0 and 28.5 kg/m2, inclusive
  • Subject is genotyped as an extensive metabolizer for CYP2D6
  • Subject agrees to sexual abstinence and/or use of a highly effective method of birth control from screening until 3 months after last dose of study medication. Examples of effective methods:

    • subject's sexual partner has been surgically sterilized (for at least 3 months prior to screening), or
    • subject/subject's sexual partner is using standard oral contraception or is practicing two (2) of the following contraceptive methods:
    • diaphragm with spermicide
    • intrauterine device
    • condoms in combination with a spermicidal cream

Exclusion Criteria:

  • Known or suspected hypersensitivity to mirabegron, propranolol or bisoprolol, or any components of the formulations used
  • Any of the liver function tests (i.e. ALT, AST) above the upper limit of normal at repeated measures
  • Any clinically significant history of bronchospasm, asthma, eczema, allergic rhinitis during the pollen season, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active hay fever)
  • Any clinically significant history of sinus bradycardia, first and second degree atrioventricular block, metabolic acidosis, Raynaud's disease, cardiogenic shock, right ventricular failure secondary to pulmonary hypertension, bronchospasms, angina, peripheral arterial occlusive disease, overt cardiac failure, congestive heart failure, sick sinus syndrome or any other cardiovascular or ECG abnormalities
  • Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the medical investigator
  • Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
  • Abnormal heart rate and/or blood pressure measurements at the pre-study visit as follows: Heart rate <50 or >90 bpm; mean systolic blood pressure <90 or >140 mmHg; mean diastolic blood pressure <40 or >90 mmHg (blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 minutes; heart rate will be measured automatically)
  • A marked baseline prolongation of QT/QTc interval after repeated measurements of > 430 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
  • PR interval > 200 ms or < 120 ms
  • Evidence of second- or third-degree atrioventricular block
  • Electrocardiographic evidence of complete left bundle branch block (LBBB), right bundle branch block or incomplete LBBB
  • Intraventricular conduction delay with QRS duration > 120 ms
  • Pathological Q-waves (defined as Q-wave > 40 ms or depth greater than 0.4 - 0.5 mV)
  • Evidence of ventricular pre-excitation
  • Use of any prescribed or OTC 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 smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the Clinical Unit
  • History of drinking more than 21 units of alcohol per week (1 unit = 200 ml of beer or 25 ml of spirits or 75 ml of wine) within 3 months prior to admission to the Clinical Unit
  • 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
  • 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, provided that the clinical study did not entail a biological compound with a long terminal half life
  • Any clinical condition, which, in the opinion of the investigator would not allow safe completion of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01284868

Paris, France, 75015
Sponsors and Collaborators
Astellas Pharma Inc
Study Director: Use Central Contact Astellas Pharma Europe B.V.

Additional Information:
Responsible Party: Disclosure Office Europe, Astellas Pharma Europe BV Identifier: NCT01284868     History of Changes
Other Study ID Numbers: 178-CL-053
2006-004653-14 ( EudraCT Number )
First Posted: January 27, 2011    Key Record Dates
Last Update Posted: July 3, 2013
Last Verified: January 2011

Keywords provided by Astellas Pharma Inc:
Mechanisms of Pharmacological Action

Additional relevant MeSH terms:
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Urological Agents
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists