An Open-label Study to Evaluate the Pharmacokinetics of YM178 After Single Oral Administration of 14C-labeled YM178 in Healthy Male Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Astellas Pharma Europe B.V.
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- The assessment of pharmacokinetic profile of radioactivity after single-dose administration of 14C-YM178, measured by whole blood and plasma concentration
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
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+
- •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
Arms & Interventions
14C-labeled YM178
Single oral administration of 14C-labeled YM178
Intervention: 14C-labeled YM178 (Drug)
Outcomes
Primary Outcomes
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]
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]
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]
plasma (Cmax, tmax, AUC0-last, AUC0-inf, t1/2 and Vz/F), urine (Ae0-24, Ae0-last, CLR and % dose excreted)
Secondary Outcomes
- Safety assessed through Adverse Events, vital signs, laboratory analyses and ECG (electrocardiogram)(Through to Day 19)