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

NCT ID: NCT01478490

Last Updated: 2014-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2002-11-30

Brief Summary

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.

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.

Conditions

Pharmacokinetics of Mirabegron; Healthy Subjects

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Treatment Arm 1A

mirabegron, poor metabolizers

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

Treatment Arm 1B

mirabegron, extensive metabolizers

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

Treatment Arm 2

mirabegron/metoprolol

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

metoprolol

Intervention Type: DRUG

oral

Interventions

mirabegron

oral

Intervention Type: DRUG

metoprolol

oral

Intervention Type: DRUG

Other Intervention Names

YM178

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Study Manager

Role: STUDY_CHAIR

Astellas Pharma Europe B.V.

Principal Investigator

Role: PRINCIPAL_INVESTIGATOR

Pharma Bio-Research Group B.V., Zuidlaren, The Netherlands

Locations

PRA International (former Pharma Bio-Research)

Zuidlaren, , Netherlands

Countries

Netherlands

References

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 beta3-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.

Reference Type: BACKGROUND

PMID: 23728524 (View on PubMed)

Other Identifiers

178-CL-005

Identifier Type: -

Identifier Source: org_study_id