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