To Compare Blood and Urine Concentrations of Mirabegron (YM178) in Healthy Poor or Extensive Metabolizers for CYP2D6 and to Assess the Effect of Mirabegron on the Metabolism of Metoprolol

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01478490
First received: November 21, 2011
Last updated: April 8, 2014
Last verified: November 2011
  Purpose

The study aims to compare blood and urine concentrations of mirabegron (YM178) in healthy poor or extensive metabolizers for CYP2D6 and to evaluate if blood levels of metoprolol change whilst being dosed at the same time with daily miragebron.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: An Open Label, One-sequence, Parallel Study to Compare the Single Dose Pharmacokinetics of YM178 in Healthy Poor or Extensive Metabolisers for CYP2D6 and to Assess the Effect of Multiple Doses of YM178 on the Metabolism of the Model Substrate Metoprolol

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetics of mirabegron assessed by plasma concentration [ Time Frame: Pre-dose until 72 hours after dosing ] [ Designated as safety issue: No ]
    Primary outcome measure for Part 1


Secondary Outcome Measures:
  • Pharmacokinetics of metoprolol assessed by plasma concentration [ Time Frame: Pre-dose until 48 hours after dosing ] [ Designated as safety issue: No ]
    Primary outcome measure for Part 2


Enrollment: 28
Study Start Date: September 2002
Study Completion Date: November 2002
Primary Completion Date: November 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm 1A
mirabegron, poor metabolizers
Drug: mirabegron
oral
Other Name: YM178
Experimental: Treatment Arm 1B
mirabegron, extensive metabolizers
Drug: mirabegron
oral
Other Name: YM178
Experimental: Treatment Arm 2
mirabegron/metoprolol
Drug: mirabegron
oral
Other Name: YM178
Drug: metoprolol
oral

Detailed Description:

The study is an open label, single center study. All subjects are genotyped for CYP2D6 before the study. Genotype expression is confirmed by dextromethorphan phenotyping.

Part I: The pharmacokinetic profile of a single dose of YM178 is compared in 8 healthy male subjects genotyped and phenotyped as poor metaboliser (PM) for CYP2D6 and in 8 healthy male subjects genotyped and phenotyped as extensive metaboliser (EM) for CYP2D6.

Part II: The effect of YM178 on the model substrate of CYP2D6 metoprolol is evaluated, using a cross-over design, in 12 healthy male subjects genotyped and phenotyped as EM for CYP2D6.

  Eligibility

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

Inclusion Criteria:

For Part I:

  • Subject genotyped and phenotyped for CYP2D6
  • Body weight between 60 and 100 kg and Body Mass Index less than or equal to 30 kg/m2

For Part II:

  • Subject genotyped and phenotyped as extensive metaboliser for CYP2D6
  • Body weight between 60 and 100 kg and Body Mass Index less than or equal to 30 kg/m2

Exclusion Criteria:

  • Known or suspected hypersensitivity to β-adrenergic receptor agonists or constituents of the formulations used
  • Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug
  • Any clinically significant history of upper gastrointestinal symptoms (such as nausea, vomiting, abdominal discomfort or upset, or heartburn) in the 4 weeks prior to admission to the Research Unit
  • Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
  • Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
  • QTc intervals of >430 msec
  • Abnormal pulse rate measurement (<40 or >90 bpm) taken by manual counting at the pre-study visit after subject has been resting in supine position for 5 min
  • Abnormal blood pressure measurements taken at the pre-study visit after subject has been resting in supine position for 5 min as follows: systolic blood pressure <95 or >160 mmHg; diastolic blood pressure <40 or >95 mmHg
  • Positive orthostatic test at screening i.e. any symptoms of dizziness, light-headedness etc. and/or a fall of ≥ 20 mmHg in systolic blood pressure after 2 min standing (preceded by 5 min. supine rest) and/or an increase in pulse rate of ≥ 20 bpm
  • Regular use of any prescribed or OTC drugs except paracetamol up to 3 g/day, in the 4 weeks prior to admission to the Research Unit OR any use of such drugs in the 2 weeks prior to admission to the Research Unit
  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: NCT01478490

Locations
Netherlands
PRA International (former Pharma Bio-Research)
Zuidlaren, Netherlands, 9471 GP
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
Principal Investigator: Principal Investigator Pharma Bio-Research Group B.V., Zuidlaren, The Netherlands
  More Information

Additional Information:
Publications:
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01478490     History of Changes
Other Study ID Numbers: 178-CL-005
Study First Received: November 21, 2011
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Astellas Pharma Inc:
Pharmacokinetics,
Mirabegron
Metoprolol
CYP2D6
Phase 1

Additional relevant MeSH terms:
Metoprolol
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014