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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01651312
First received: July 23, 2012
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Metabolic Processes
Drug: 14C-labeled YM178
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-label Study to Evaluate the Pharmacokinetics of YM178 After Single Oral Administration of 14C-labeled YM178 in Healthy Male Volunteers

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • The assessment of pharmacokinetic profile of radioactivity after single-dose administration of 14C-YM178, measured by whole blood and plasma concentration [ Time Frame: Baseline to Day 5 (optional (Day 6-8) [maximum of 19 assessments] ] [ Designated as safety issue: No ]
    Cmax, tmax, AUC0-last, AUC0-inf, t1/2 and the blood-to-plasma ratio (Ratio Cb/p)

  • The excretion rate and cumulative excretion of radioactivity in urine, feces and expired air after single-dose administration of 14C-YM178 [ Time Frame: Baseline to Day 5 (optional (Day 6-8) [maximum of 10 assessments] ] [ Designated as safety issue: No ]
  • The assessment of pharmacokinetic profile of parent YM178 after single-dose administration of 14C-YM178, measured plasma and urine concentration [ Time Frame: Baseline to Day 5 (optional (Day 6-8) [maximum of 19 assessments] ] [ Designated as safety issue: No ]
    plasma (Cmax, tmax, AUC0-last, AUC0-inf, t1/2 and Vz/F), urine (Ae0-24, Ae0-last, CLR and % dose excreted)


Secondary Outcome Measures:
  • Safety assessed through Adverse Events, vital signs, laboratory analyses and ECG (electrocardiogram) [ Time Frame: Through to Day 19 ] [ Designated as safety issue: Yes ]

Enrollment: 4
Study Start Date: January 2003
Study Completion Date: February 2003
Primary Completion Date: February 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 14C-labeled YM178
Single oral administration of 14C-labeled YM178
Drug: 14C-labeled YM178
oral solution (1.85 MBq)
Other Names:
  • mirabegron
  • Myrebtriq

Detailed Description:

Four subjects are studied in one group. Each subject stays in the clinic for 6 days, and receives a single oral dose of 14C-labeled YM178. Blood, plasma, urine, feces and expired air are collected for 96h after dosing.

If 14C-radioactivity quick counts show that radioactivity in urine or feces is above acceptable limits (ie. > 50 dpm/ml in urine; >75 dpm in 400 mg feces) on day 5, subjects are requested to stay in the clinic until the levels decrease. If, after 3 days, radioactivity is still > 50 dpm/ml in urine and/or >75 dpm in 400 mg feces, urine and/or feces is collected at home, until the amount of radioactivity decreases.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.
  • 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
  • Subjects having received YM178 previously
  • Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column)), during work or during participation in a clinical trial in the previous year
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01651312

Locations
Netherlands
Pharma Bio-Research Group B.V.
Zuidlaren, Netherlands, 9471 GP
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

Additional Information:
Publications:
Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01651312     History of Changes
Other Study ID Numbers: 178-CL-007
Study First Received: July 23, 2012
Last Updated: September 4, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Astellas Pharma Inc:
Radioactivity
Excretion rate
Human subjects
Pharmacokinetics
YM178
Radio-labeled
Phase 1

ClinicalTrials.gov processed this record on April 17, 2014