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

NCT01478490 | Completed Phase 1

• 1 other identifier: 178-CL-005
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics of Mirabegron; Healthy Subjects

Keywords

Pharmacokinetics,; Mirabegron; Metoprolol; CYP2D6; Phase 1

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of mirabegron assessed by plasma concentration

  Primary outcome measure for Part 1

  Pre-dose until 72 hours after dosing

Secondary Outcomes (1)

• Pharmacokinetics of metoprolol assessed by plasma concentration

  Pre-dose until 48 hours after dosing

Study Arms (3)

Treatment Arm 1A

EXPERIMENTAL

mirabegron, poor metabolizers

Drug: mirabegron

Treatment Arm 1B

EXPERIMENTAL

mirabegron, extensive metabolizers

Drug: mirabegron

Treatment Arm 2

EXPERIMENTAL

mirabegron/metoprolol

Drug: mirabegron; Drug: metoprolol

Interventions

mirabegron DRUG

oral

Also known as: YM178

Treatment Arm 1A; Treatment Arm 1B; Treatment Arm 2

metoprolol DRUG

oral

Treatment Arm 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (1)

PRA International (former Pharma Bio-Research)

Zuidlaren, 9471 GP, Netherlands

Location

Related 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 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.

  PMID: 23728524 BACKGROUND

MeSH Terms

Interventions

mirabegron; Metoprolol

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Clinical Study Manager

  Astellas Pharma Europe B.V.

  STUDY CHAIR

• Principal Investigator

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2011
• First Posted: November 23, 2011
• Study Start: September 1, 2002
• Primary Completion: November 1, 2002
• Study Completion: November 1, 2002
• Last Updated: April 10, 2014

Record last verified: 2011-11

Locations

NL (1)