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

Sponsor

Astellas Pharma Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT01284868

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Jul 1, 2009

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirabegron	Drug: mirabegron oral Other Names: YM178 Drug: Bisoprolol oral Drug: propranolol oral Drug: placebo oral

Arm

Intervention/Treatment

Experimental: Mirabegron

Drug: mirabegron

oral

Other Names:

YM178

Drug: Bisoprolol

oral

Drug: propranolol

oral

Drug: placebo

oral

Outcome Measures

Primary Outcome Measures

Plasma renin activity [12 hours]
Impedance cardiography [12 hours]

Secondary Outcome Measures

Pharmacokinetic assessment of mirabegron by analysis of plasma samples [12 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

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