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

Healthy Subjects Clinical Trial

Official title:

An Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of YM178 on the Pharmacokinetics of the CYP2D6 Substrate Desipramine in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01478568
• Other study ID #: 178-CL-058
• Secondary ID: 2008-000215-15
• Status: Completed
• Phase: Phase 1
• First received: November 21, 2011
• Last updated: April 8, 2014
• Start date: October 2008
• Est. completion date: January 2009

Study information

• Verified date: July 2013
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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)

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacokinetics of Mirabegron

Intervention

Drug:
• mirabegron
oral
• desipramine
oral

Locations

Country	Name	City	State
France	SGS Aster	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

France, 

References & Publications (1)

Krauwinkel W, Dickinson J, Schaddelee M, Meijer J, Tretter R, van de Wetering J, Strabach G, van Gelderen M. The effect of mirabegron, a potent and selective ß3-adrenoceptor agonist, on the pharmacokinetics of CYP2D6 substrates desipramine and metoprolol. Eur J Drug Metab Pharmacokinet. 2014 Mar;39(1):43-52. doi: 10.1007/s13318-013-0133-1. Epub 2013 Jun 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of desipramine assessed by plasma concentration while at steady state levels of mirabegron		Pre-dose until 72 hours after dosing	No
Secondary	Monitoring of safety and tolerability through assessment of vital signs, ECG, clinical safety laboratory and adverse events		Baseline until End of Study Visit (7 to 14 days after last dose)	Yes
Secondary	Pharmacokinetics of desipramine assessed by plasma concentration after wash-out of mirabegron		Pre-dose until 72 hours after wash-out	No

External Links

•   Link to Results on JAPIC