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

Astellas

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects; Mild and Moderate Hepatic Impairment; Pharmacokinetics

Treatments: Drug: mirabegron

Study type: Interventional

Funder types: Industry

Identifiers

NCT01579461

2008-000210-77 (EudraCT Number)

178-CL-039

Details and patient eligibility

About

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

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 4 patient groups

mild hepatic impairment

Experimental group

Treatment:

Drug: mirabegron

moderate hepatic impairment

Experimental group

Treatment:

Drug: mirabegron

healthy volunteers (matched with mild hepatic)

Experimental group

Treatment:

Drug: mirabegron

healthy volunteers (matched with moderate hepatic)

Experimental group

Treatment:

Drug: mirabegron