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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Additional relevant MeSH terms:
Mirabegron
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014