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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01478568
First received: November 21, 2011
Last updated: April 8, 2014
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Pharmacokinetics of Mirabegron
Healthy Subjects
Drug: mirabegron
Drug: desipramine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetics of desipramine assessed by plasma concentration while at steady state levels of mirabegron [ Time Frame: Pre-dose until 72 hours after dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Monitoring of safety and tolerability through assessment of vital signs, ECG, clinical safety laboratory and adverse events [ Time Frame: Baseline until End of Study Visit (7 to 14 days after last dose) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of desipramine assessed by plasma concentration after wash-out of mirabegron [ Time Frame: Pre-dose until 72 hours after wash-out ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: October 2008
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mirabegron / desipramine Drug: mirabegron
oral
Other Name: YM178
Drug: desipramine
oral
Other Names:
  • pertofrane
  • norpramin

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478568

Locations
France
SGS Aster
Paris, France, 75015
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

Additional Information:
Publications:
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01478568     History of Changes
Other Study ID Numbers: 178-CL-058, 2008-000215-15
Study First Received: November 21, 2011
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Astellas Pharma Inc:
Pharmacokinetics
Mirabegron
Phase 1

Additional relevant MeSH terms:
Mirabegron
Desipramine
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Enzyme Inhibitors
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014