Clinical trial NCT01579461: A Study to Investigate the Effect of Mirabegron (YM178) on Subjects With Mild or Moderate Hepatic Impairment Compared to Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Healthy Subjects
Mild and Moderate Hepatic Impairment
Keywords: Pharmacokinetics
mirabegron
hepatic impairment
Phase 1
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-04-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Assess the single dose pharmacokinetics of Mirabegron in healthy subjects compared to subjects with hepatic impairment
timeFrame: Day 1 - Day 11
Secondary outcomes:
measure: Safety assessed by incidence of adverse events, lab tests, physical exam, ECG and vital signs
timeFrame: Day 1 - End of Study (Up to Day 19)
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: FNsP Bratislava, nemocnica akad. L. Dérera; Klinika pracovného lekárstva a toxikológie
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_CHAIR
References:
citation: 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.