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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01579461
• Other study ID #: 178-CL-039
• Secondary ID: 2008-000210-77
• Status: Completed
• Phase: Phase 1
• First received: April 16, 2012
• Last updated: September 4, 2013
• Start date: November 2008
• Est. completion date: April 2009

Study information

• Verified date: September 2013
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSlovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects
• Liver Diseases
• Mild and Moderate Hepatic Impairment
• Pharmacokinetics

Intervention

Drug:
• mirabegron
oral

Locations

Country	Name	City	State
Slovakia	FNsP Bratislava, nemocnica akad. L. Dérera; Klinika pracovného lekárstva a toxikológie	Bratislava

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Country where clinical trial is conducted

Slovakia, 

References & Publications (1)

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, Kupcová 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the single dose pharmacokinetics of Mirabegron in healthy subjects compared to subjects with hepatic impairment	AUCinf and Cmax	Day 1 - Day 11	No
Secondary	Safety assessed by incidence of adverse events, lab tests, physical exam, ECG and vital signs		Day 1 - End of Study (Up to Day 19)	No

External Links

•   Link to Results on JAPIC