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

Astellas

Status and phase

Completed

Phase 1

Conditions

Healthy Subjects

Pharmacokinetics of Mirabegron

Treatments

Drug: mirabegron

Drug: metoprolol

Study type

Interventional

Funder types

Industry

Identifiers

NCT01478490

178-CL-005

Details and patient eligibility

About

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.

Full 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.

Enrollment

28 patients

Sex

Male

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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