A Study to Investigate the Effect of Mirabegron (YM178) on Subjects With Mild or Moderate Hepatic Impairment Compared to Healthy Subjects
Primary Purpose
Pharmacokinetics, Healthy Subjects, Mild and Moderate Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
Slovakia
Study Type
Interventional
Intervention
mirabegron
Sponsored by

About this trial
This is an interventional basic science trial for Pharmacokinetics focused on measuring Pharmacokinetics, mirabegron, hepatic impairment, Phase 1
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
Sites / Locations
- FNsP Bratislava, nemocnica akad. L. Dérera; Klinika pracovného lekárstva a toxikológie
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
mild hepatic impairment
moderate hepatic impairment
healthy volunteers (matched with mild hepatic)
healthy volunteers (matched with moderate hepatic)
Arm Description
Outcomes
Primary Outcome Measures
Assess the single dose pharmacokinetics of Mirabegron in healthy subjects compared to subjects with hepatic impairment
AUCinf and Cmax
Secondary Outcome Measures
Safety assessed by incidence of adverse events, lab tests, physical exam, ECG and vital signs
Full Information
NCT ID
NCT01579461
First Posted
April 16, 2012
Last Updated
September 4, 2013
Sponsor
Astellas Pharma Europe B.V.
1. Study Identification
Unique Protocol Identification Number
NCT01579461
Brief Title
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
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Europe B.V.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pharmacokinetics, Healthy Subjects, Mild and Moderate Hepatic Impairment
Keywords
Pharmacokinetics, mirabegron, hepatic impairment, Phase 1
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
mild hepatic impairment
Arm Type
Experimental
Arm Title
moderate hepatic impairment
Arm Type
Experimental
Arm Title
healthy volunteers (matched with mild hepatic)
Arm Type
Experimental
Arm Title
healthy volunteers (matched with moderate hepatic)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
mirabegron
Other Intervention Name(s)
YM178
Intervention Description
oral
Primary Outcome Measure Information:
Title
Assess the single dose pharmacokinetics of Mirabegron in healthy subjects compared to subjects with hepatic impairment
Description
AUCinf and Cmax
Time Frame
Day 1 - Day 11
Secondary Outcome Measure Information:
Title
Safety assessed by incidence of adverse events, lab tests, physical exam, ECG and vital signs
Time Frame
Day 1 - End of Study (Up to Day 19)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Study Manager
Organizational Affiliation
Astellas Pharma Europe B.V.
Official's Role
Study Chair
Facility Information:
Facility Name
FNsP Bratislava, nemocnica akad. L. Dérera; Klinika pracovného lekárstva a toxikológie
City
Bratislava
ZIP/Postal Code
83305
Country
Slovakia
12. IPD Sharing Statement
Citations:
PubMed Identifier
23208320
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.
Results Reference
background
Links:
URL
http://www.clinicaltrials.jp/user/ctrDetail_e.jsp?resultId=797
Description
Link to Results on JAPIC
Learn more about this trial
A Study to Investigate the Effect of Mirabegron (YM178) on Subjects With Mild or Moderate Hepatic Impairment Compared to Healthy Subjects
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