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

An Open Label Single Dose Study to Investigate the Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of YM178 Compared With Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics; Mild and Moderate Hepatic Impairment
• Intervention / Treatment: Drug: mirabegron

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Slovakia
  • Bratislava, Slovakia, 83305
    • FNsP Bratislava, nemocnica akad. L. Dérera; Klinika pracovného lekárstva a toxikológie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mild hepatic impairment	Drug: mirabegron; oral; Other Names: YM178
Experimental: moderate hepatic impairment	Drug: mirabegron; oral; Other Names: YM178
Experimental: healthy volunteers (matched with mild hepatic)	Drug: mirabegron; oral; Other Names: YM178
Experimental: healthy volunteers (matched with moderate hepatic)	Drug: mirabegron; oral; Other Names: YM178

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the single dose pharmacokinetics of Mirabegron in healthy subjects compared to subjects with hepatic impairment	AUCinf and Cmax	Day 1 - Day 11

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety assessed by incidence of adverse events, lab tests, physical exam, ECG and vital signs	Day 1 - End of Study (Up to Day 19)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: April 16, 2012
• First Submitted That Met QC Criteria: April 17, 2012
• First Posted (Estimate): April 18, 2012

Study Record Updates

• Last Update Posted (Estimate): September 5, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase 1; mirabegron; hepatic impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron
• Other Study ID Numbers: 178-CL-039; 2008-000210-77 (EudraCT Number)