A Study to Find Out How Much Mirabegron Gets Into the Body After Dosing With a Tablet Formulation

A Single Dose, Open Label, Randomized, Two-period Cross Over Study in Healthy Male Subjects to Assess the Absolute Bioavailability of YM178 OCAS-M Formulation

A study to evaluate how much of the active compound of mirabegron comes into the blood circulation when given as a controlled-release pill as compared to given intravenously.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Bioavailability; Pharmacokinetics of Mirabegron
• Intervention / Treatment: Drug: mirabegron OCAS; Drug: mirabegron

Detailed Description

All participants will receive both oral and iv formulations, separated by a washout period. Treatment arm A will receive a lower dose of mirabegron; Treatment arm B will receive a higher dose of mirabegron.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands, 9470 AE
    • Pharma Bio Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body weight between 60.0 and 100.0 kg and Body Mass Index between 18.0 and 30.0 kg/m2

Exclusion Criteria:

• Known or suspected hypersensitivity to β-adrenergic receptor agonists or constituents of the formulations used
• Clinically significant elevation of serum creatinine or liver enzymes as evidenced by creatinine >150 ųmol/L; ASAT, ALAT or LDH> 2x ULN; ɣ-GT > 3x ULN and/or abnormal serum bilirubin
• Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug
• Subjects taking β blockers or β agonists (eye drops allowed)
• Any clinically significant history of upper gastrointestinal symptoms (such as nausea, vomiting, abdominal discomfort or upset, or heartburn) in the 4 weeks prior to the first admission to the Research Unit
• Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, ophthalmologic, renal, hepatic, neurological, dermatological, psychiatric or metabolic
• Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
• QTcB interval of > 430 (mean QTcB of two measurements > 430msec)
• Abnormal pulse rate measurement (<40 or >90 bpm) at the pre-study visit after subject has been resting in supine position for 5 min.

• Abnormal blood pressure measurements taken at the pre-study visit after subject has been resting in supine position for 5 min as follows:

  • Systolic blood pressure <95 or >160 mmHg
  • Diastolic blood pressure <40 or >90 mmHg
• Positive orthostatic test at screening i.e. any symptoms of dizziness, light-headedness etc. and a fall of > 20 mmHg in systolic blood pressure after 2 min standing and an increase in pulse rate of ≥ 20 bpm
• Regular use of any prescribed or OTC drugs except paracetamol up to 3 g/day, in the 4 weeks prior to admission to the Research Unit OR any use of such drugs in the 2 weeks prior to first admission to the Research Unit

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm A; low dose of mirabegron	Drug: mirabegron OCAS; oral administration; Other Names: YM178 OCAS; Drug: mirabegron; iv administration; Other Names: YM178
Experimental: Treatment Arm B; high dose of mirabegron	Drug: mirabegron OCAS; oral administration; Other Names: YM178 OCAS; Drug: mirabegron; iv administration; Other Names: YM178

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of 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

• Eltink C, Lee J, Schaddelee M, Zhang W, Kerbusch V, Meijer J, van Marle S, Grunenberg N, Kowalski D, Drogendijk T, Moy S, Iitsuka H, van Gelderen M, Matsushima H, Sawamoto T. Single dose pharmacokinetics and absolute bioavailability of mirabegron, a beta(3)-adrenoceptor agonist for treatment of overactive bladder. Int J Clin Pharmacol Ther. 2012 Nov;50(11):838-50. doi: 10.5414/CP201782.

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2006

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): June 27, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase 1; Mirabegron
• 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-033