To Evaluate the Blood and Urine Concentration and the Safety and Tolerability of Increasing Repeated Doses of Mirabegron (YM178) OCAS in Healthy Young and Elderly Males and Healthy Young and Elderly Females

Double-blind, Randomized, Placebo-controlled, Dose-escalating, Exploratory Study to Investigate the Pharmacokinetics, Safety and Tolerability of Multiple Doses of YM178 OCAS-M in Healthy Young Male and Female Subjects and Healthy Elderly Male and Female Subjects

The study aimed to compare age and gender differences for increasing doses of mirabegron when given to healthy young and elderly males and healthy young and elderly females.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics
• Intervention / Treatment: Drug: Placebo; Drug: mirabegron OCAS

Detailed Description

Each subject will receive a single dose of mirabegron OCAS-M or placebo on Day 2, followed by multiple dosing (qd) for 10 days (Day 5-14).

Young subjects will be divided into 4 groups and elderly subjects into 2 groups. Dosage will be different among groups.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 358 CJ
    • Kendle Nederland
  • Zuidlaren, Netherlands, 9470 AE
    • Pharma Bio Research

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:

• Healthy young subjects aged 18-55 years (inclusive)
• Healthy elderly subjects aged 65-80 years (inclusive)
• Body weight between 60.0 and 100.0 kg (male) or between 50.0 and 90.0 kg (female), and Body Mass Index between 18.0 and 30.0 kg/m2

Exclusion Criteria:

• Known or suspected hypersensitivity to β-adrenergic receptor agonists or any components of the formulation used
• Any of the liver function tests (i.e. ALT, AST and bilirubin) above the upper limit of normal at repeated measures
• Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the medical investigator.
• Any clinically significant abnormality following the investigator's review of the pre-study physical examination, electrocardiogram (ECG) and clinical laboratory tests
• Subjects taking β blockers or β agonists
• Use of any prescribed or Over-the-counter (OTC) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day)
• Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampicin) in the 3 months prior to admission to the Clinical Unit
• Donation of blood or blood products within 3 months prior to admission to the Clinical Unit
• Any use of drugs of abuse, or smoking of more than 10 cigarettes (or equivalent) or more than 21 units of alcohol per week within the 3 months prior to study
• Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Arm A; mirabegron	Drug: mirabegron OCAS; oral; Other Names: YM178 OCAS
PLACEBO_COMPARATOR: Treatment Arm B; matching placebo	Drug: Placebo; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of mirabegron assessed by plasma concentration	Pre-dose until 72 hours after dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events	Baseline until 72 hours after dosing

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• Krauwinkel W, van Dijk J, Schaddelee M, Eltink C, Meijer J, Strabach G, van Marle S, Kerbusch V, van Gelderen M. Pharmacokinetic properties of mirabegron, a beta3-adrenoceptor agonist: results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women. Clin Ther. 2012 Oct;34(10):2144-60. doi: 10.1016/j.clinthera.2012.09.010.

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ACTUAL): October 1, 2005
• Study Completion (ACTUAL): October 1, 2005

Study Registration Dates

• First Submitted: November 21, 2011
• First Submitted That Met QC Criteria: November 21, 2011
• First Posted (ESTIMATE): November 23, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): July 2, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase 1; Mirabegron; Dose-Escalation
• Additional Relevant MeSH Terms: 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-031