Metabolic Processes
Conditions
Keywords
Radioactivity, Excretion rate, Human subjects, Pharmacokinetics, YM178, Radio-labeled, Phase 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.
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.
Interventions
DRUG14C-labeled YM178
oral solution (1.85 MBq)
Sponsors
Astellas Pharma Europe B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
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+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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Safety assessed through Adverse Events, vital signs, laboratory analyses and ECG (electrocardiogram) | Through to Day 19 |
Countries
Netherlands
Outcome results
None listed