A Study to Assess the Systemic Pharmacokinetics, Metabolism and Excretion Routes of YM178 in Man, After Administration of Radio-labeled YM178

NCT01651312 | Completed Phase 1

• 1 other identifier: 178-CL-007
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to assess the routes and the extent of metabolism and excretion of YM178 after a single dose of 14C-radiolabeled YM178 administered as a drinking solution in healthy male volunteers.

Conditions

Metabolic Processes

Keywords

Radioactivity; Excretion rate; Human subjects; Pharmacokinetics; YM178; Radio-labeled; Phase 1

Outcome Measures

Primary Outcomes (3)

• The assessment of pharmacokinetic profile of radioactivity after single-dose administration of 14C-YM178, measured by whole blood and plasma concentration

  Cmax, tmax, AUC0-last, AUC0-inf, t1/2 and the blood-to-plasma ratio (Ratio Cb/p)

  Baseline to Day 5 (optional (Day 6-8) [maximum of 19 assessments]

• The excretion rate and cumulative excretion of radioactivity in urine, feces and expired air after single-dose administration of 14C-YM178

  Baseline to Day 5 (optional (Day 6-8) [maximum of 10 assessments]

• The assessment of pharmacokinetic profile of parent YM178 after single-dose administration of 14C-YM178, measured plasma and urine concentration

  plasma (Cmax, tmax, AUC0-last, AUC0-inf, t1/2 and Vz/F), urine (Ae0-24, Ae0-last, CLR and % dose excreted)

  Baseline to Day 5 (optional (Day 6-8) [maximum of 19 assessments]

Secondary Outcomes (1)

• Safety assessed through Adverse Events, vital signs, laboratory analyses and ECG (electrocardiogram)

  Through to Day 19

Study Arms (1)

14C-labeled YM178

EXPERIMENTAL

Single oral administration of 14C-labeled YM178

Drug: 14C-labeled YM178

Interventions

14C-labeled YM178 DRUG

oral solution (1.85 MBq)

Also known as: mirabegron, Myrebtriq

14C-labeled YM178

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body weight between 60 and 100 kg, and BMI ≤30 kg/m2

You may not qualify if:

• Known or suspected hypersensitivity to β-adrenergic receptor agonists or constituents of the formulations used
• Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug
• Any clinically significant history of upper gastrointestinal symptoms (such as nausea, vomiting, abdominal discomfort or upset, or heartburn) in the 4 weeks prior to admission to the Research Unit
• Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
• Abnormal pulse rate measurement (\<40 or \>90 bpm) taken by manual counting 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 \>95 mmHg.
• Positive orthostatic test at screening i.e. any symptoms of dizziness, light-headedness etc. and/or a fall of ≥ 20 mmHg in systolic blood pressure after 2 min standing (preceded by 5 min. supine rest) and/or an increase in pulse rate of ≥ 20 bpm
• Regular use of any prescribed or OTC (over the counter) 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 admission to the Research Unit
• History of drug abuse at any time, OR any use of drugs of abuse within 3 months prior to admission to the Research Unit
• History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the Research Unit
• History of drinking more than 21 units of alcohol per week (1 unit = 270 cc of beer or 40 cc of spirits or 1 glass of wine) within 3 months prior to admission to the Research Unit
• Donation of blood or blood products within 3 months prior to admission to the Research Unit
• Positive serology test for HBsAg, HAV IgM, anti-HCV or anti-HIV 1+2.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Pharma Bio-Research Group B.V.

Zuidlaren, 9471 GP, Netherlands

Location

Related Publications (1)

• Takusagawa S, van Lier JJ, Suzuki K, Nagata M, Meijer J, Krauwinkel W, Schaddelee M, Sekiguchi M, Miyashita A, Iwatsubo T, van Gelderen M, Usui T. Absorption, metabolism and excretion of [(14)C]mirabegron (YM178), a potent and selective beta(3)-adrenoceptor agonist, after oral administration to healthy male volunteers. Drug Metab Dispos. 2012 Apr;40(4):815-24. doi: 10.1124/dmd.111.043588. Epub 2012 Jan 23.

  PMID: 22269146 BACKGROUND

MeSH Terms

Interventions

mirabegron

Study Officials

• Clinical Study Manager

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 27, 2012
• Study Start: January 1, 2003
• Primary Completion: February 1, 2003
• Study Completion: February 1, 2003
• Last Updated: September 5, 2013

Record last verified: 2013-09

Locations

NL (1)