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

NCT ID: NCT01284868

Last Updated: 2013-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2009-11-30

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.

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.

Conditions

Healthy Volunteers; Pharmacodynamics of Mirabegron

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Mirabegron

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

Bisoprolol

Intervention Type: DRUG

oral

propranolol

Intervention Type: DRUG

oral

placebo

Intervention Type: DRUG

oral

Interventions

mirabegron

oral

Intervention Type: DRUG

Bisoprolol

oral

Intervention Type: DRUG

propranolol

oral

Intervention Type: DRUG

placebo

oral

Intervention Type: DRUG

Other Intervention Names

YM178

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Astellas Pharma Europe BV

Principal Investigators

Use Central Contact

Role: STUDY_DIRECTOR

Astellas Pharma Europe B.V.

Locations

Paris, , France

Countries

France

Other Identifiers

2006-004653-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

178-CL-053

Identifier Type: -

Identifier Source: org_study_id