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

Tracking Information
First Submitted Date ICMJE	April 16, 2012
First Posted Date ICMJE	April 18, 2012
Last Update Posted Date	September 5, 2013
Study Start Date ICMJE	November 2008
Actual Primary Completion Date	April 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 17, 2012)	Assess the single dose pharmacokinetics of Mirabegron in healthy subjects compared to subjects with hepatic impairment [ Time Frame: Day 1 - Day 11 ]; AUCinf and Cmax
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01579461 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 17, 2012)	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) ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study to Investigate the Effect of Mirabegron (YM178) on Subjects With Mild or Moderate Hepatic Impairment Compared to Healthy Subjects
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
Condition ICMJE	Pharmacokinetics; Healthy Subjects; Mild and Moderate Hepatic Impairment
Intervention ICMJE	Drug: mirabegron; oral; Other Name: YM178
Study Arms	Experimental: mild hepatic impairment Intervention: Drug: mirabegron; Experimental: moderate hepatic impairment Intervention: Drug: mirabegron; Experimental: healthy volunteers (matched with mild hepatic) Intervention: Drug: mirabegron; Experimental: healthy volunteers (matched with moderate hepatic) Intervention: Drug: mirabegron
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, Kupčová 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: April 17, 2012)	32
Original Actual Enrollment ICMJE	Same as current
Actual Study Completion Date	April 2009
Actual Primary Completion Date	April 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Slovakia
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01579461
Other Study ID Numbers ICMJE	178-CL-039; 2008-000210-77 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
Study Sponsor ICMJE	Astellas Pharma Europe B.V.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
PRS Account	Astellas Pharma Inc
Verification Date	September 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP