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

Phase 1

Completed

• Conditions: Metabolic Processes
• Interventions: Drug: 14C-labeled YM178

• Registration Number: NCT01651312
• Lead Sponsor: Astellas Pharma Europe B.V.

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.

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.

Study Timeline

• Study Start: 2003-01
• Primary Completion: 2003-02
• Study Completion: 2003-02
• Study First Submitted: 2012-07-23
• Study First Submitted QC: 2012-07-25
• Study First Posted: 2012-07-27
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-04
• Last Update Posted: 2013-09-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
14C-labeled YM178	14C-labeled YM178	Single oral administration of 14C-labeled YM178

Primary Outcome Measures

Name	Time	Method
The assessment of pharmacokinetic profile of radioactivity after single-dose administration of 14C-YM178, measured by whole blood and plasma concentration	Baseline to Day 5 (optional (Day 6-8) [maximum of 19 assessments]	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	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	Baseline to Day 5 (optional (Day 6-8) [maximum of 19 assessments]	plasma (Cmax, tmax, AUC0-last, AUC0-inf, t1/2 and Vz/F), urine (Ae0-24, Ae0-last, CLR and % dose excreted)

Secondary Outcome Measures

Name	Time	Method
Safety assessed through Adverse Events, vital signs, laboratory analyses and ECG (electrocardiogram)	Through to Day 19

Trial Locations

Locations (1)

Pharma Bio-Research Group B.V.; 🇳🇱 Zuidlaren, Netherlands