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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Pharmacokinetics of Mirabegron, Bioavailability, Healthy Subjects

Intervention / Treatment
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* Drug: mirabegron OCAS
* Drug: mirabegron


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A<br>low dose of mirabegron | Drug: mirabegron OCAS<br>* oral administration<br>* Other names: YM178 OCAS;Drug: mirabegron<br>* iv administration<br>* Other names: YM178;|
| Experimental: Treatment Arm B<br>high dose of mirabegron | Drug: mirabegron OCAS<br>* oral administration<br>* Other names: YM178 OCAS;Drug: mirabegron<br>* iv administration<br>* Other names: YM178;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of pharmacokinetics of mirabegron assessed by plasma concentration |  | Pre-dose until 72 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Mirabegron, Phase 1