A Study to Investigate the Effect of Mirabegron (YM178) on Subjects With Mild or Moderate Hepatic Impairment Compared to Healthy Subjects

NCT ID: NCT01579461

Last Updated: 2013-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2009-04-30

Brief Summary

The study aims to investigate and compare the effect of Mirabegron (YM178) on subjects with mild and moderate hepatic impairment compared to healthy subjects.

Detailed Description

Healthy subjects and subjects with mild and moderate hepatic impairment are admitted on Day 1. Subjects receive a single oral dose of Mirabegron in the morning of Day 1 and will remain in the unit till Day 5 with outpatient visits on Days 6 and 7 for healthy subjects and Days 6, 7, 9 and 11 for subjects with hepatic impairment. Blood sampling for PK assessment will be up to 144 hrs post dose for healthy subjects and up to 240 hrs post dose for subjects with hepatic impairment. An additional blood sample was obtained for all subjects 4 hrs post dose for protein binding.

Conditions

Pharmacokinetics; Healthy Subjects; Mild and Moderate Hepatic Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

mild hepatic impairment

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

moderate hepatic impairment

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

healthy volunteers (matched with mild hepatic)

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

healthy volunteers (matched with moderate hepatic)

Group Type: EXPERIMENTAL

mirabegron

Intervention Type: DRUG

oral

Interventions

mirabegron

oral

Intervention Type: DRUG

Other Intervention Names

YM178

Eligibility Criteria

Inclusion Criteria

• Body Mass Index more than or equal to 18.0 and less than 32.0 kg/m2 (men and women)
• Subject is genotyped as an extensive metabolizer for CYP2D6
• For subjects with mild/moderate hepatic impairment: Hepatic dysfunction scored as mild impairment ((between 5-6 in the Child-Pugh's classification) and moderate impairment (between 7-9 in the Child-Pugh's classification)
• Healthy subject with normal hepatic function

Exclusion Criteria

• Known or suspected hypersensitivity to mirabegron or any components of the formulations used
• A marked prolongation at screening of QT/QTC interval demonstrated by a mean QTcF interval >450 ms for male subjects and a mean QTcF interval >470 ms for female subjects (based on 3 ECGs)
• Abnormal pulse rate and/or blood pressure measurements at the pre-study visit taken in triplicate by means of an automatic device, after subject has been resting in supine position for 5 min: •Pulse rate <40 or >90 bpm; Mean systolic blood pressure <90 or >160 mmHg; Mean diastolic blood pressure <40 or >95 mmHg
• Healthy subjects: use of any prescribed or OTC drugs (except paracetamol, with a maximum of 3g/day) in the 2 weeks prior to admission to the clinical unit

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Study Manager

Role: STUDY_CHAIR

Astellas Pharma Europe B.V.

Locations

FNsP Bratislava, nemocnica akad. L. Dérera; Klinika pracovného lekárstva a toxikológie

Bratislava, , Slovakia

Countries

Slovakia

References

Dickinson J, Lewand M, Sawamoto T, Krauwinkel W, Schaddelee M, Keirns J, Kerbusch V, Moy S, Meijer J, Kowalski D, Morton R, Lasseter K, Riff D, Kupcova V, van Gelderen M. Effect of renal or hepatic impairment on the pharmacokinetics of mirabegron. Clin Drug Investig. 2013 Jan;33(1):11-23. doi: 10.1007/s40261-012-0031-3.

Reference Type: BACKGROUND

PMID: 23208320 (View on PubMed)

Other Identifiers

2008-000210-77

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

178-CL-039

Identifier Type: -

Identifier Source: org_study_id