To Evaluate the Effect of Mirabegron (YM178) on Blood Levels of Desipramine When They Are Taken Together

Astellas

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects; Pharmacokinetics of Mirabegron

Treatments: Drug: desipramine; Drug: mirabegron

Study type: Interventional

Funder types: Industry

Identifiers

NCT01478568

178-CL-058

2008-000215-15 (EudraCT Number)

Details and patient eligibility

About

The study aims to evaluate if blood levels of desipramine change whilst being dosed at the same time with daily mirabegron.

Full description

This is an open-label, one-sequence crossover design study to evaluate the drug-drug interaction between mirabegron and desipramine. The effect of mirabegron on the plasma concentration of desipramine will be evaluated after 13 day repeated administration. The recovery of CYP2D6 activity is also being explored by comparing the pharmacokinetic profiles of desipramine after a 2 week wash-out period.

Enrollment: 28 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Body Mass Index between 18.5 and 30.0 kg/m2 inclusive
• Subject is genotyped and phenotyped as an extensive metabolizer for CYP2D6

Exclusion criteria

• Known or suspected hypersensitivity to YM178 or any of the components of the formulation used
• Known or suspected hypersensitivity to desipramine or any of the components of the formulation used
• Pregnant or breast feeding within 6 months before screening assessment
• Any clinical history of major depressive disorder, cardiovascular disease, urinary retention, glaucoma, thyroid disease and/or seizure disorder
• Any of the liver function tests (i.e. Alanine Aminotransferase (ALT), Asparate Aminotransferase (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 abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
• Abnormal pulse rate and/or blood pressure measurements at the pre-study visit as follows: pulse rate <40 or >90 bpm; mean systolic blood pressure >140 mmHg; mean diastolic blood pressure >90 mmHg (blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse rate 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)

Trial design

28 participants in 1 patient group

mirabegron / desipramine

Experimental group

Treatment:

Drug: desipramine

Drug: mirabegron