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

NCT01284868 | Completed Phase 1

• 2 other identifiers: 178-CL-0532006-004653-14
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers; Pharmacodynamics of Mirabegron

Keywords

Mechanisms of Pharmacological Action; Pharmacodynamics; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Plasma renin activity

  12 hours

• Impedance cardiography

  12 hours

Secondary Outcomes (1)

• Pharmacokinetic assessment of mirabegron by analysis of plasma samples

  12 hours

Study Arms (1)

Mirabegron

EXPERIMENTAL

Drug: mirabegron; Drug: Bisoprolol; Drug: propranolol; Drug: placebo

Interventions

mirabegron DRUG

oral

Also known as: YM178

Mirabegron

Bisoprolol DRUG

oral

Mirabegron

propranolol DRUG

oral

Mirabegron

placebo DRUG

oral

Mirabegron

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (1)

Unknown Facility

Paris, 75015, France

Location

MeSH Terms

Interventions

mirabegron; Bisoprolol; Propranolol

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Use Central Contact

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 23, 2011
• First Posted: January 27, 2011
• Study Start: July 1, 2009
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: July 3, 2013

Record last verified: 2011-01

Locations

FR (1)