A study to see how [14C]-S-033188 is taken up, broken down and removed from the body
- Conditions
- Influenza virus infectionRespiratoryInfluenza, virus not identified
- Registration Number
- ISRCTN74587134
- Lead Sponsor
- Shionogi Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 6
1. Male subjects who are able to understand the study and comply with all study procedures, and willing to provide written informed consent before screening
2. Male subjects aged from 30 years to 65 years inclusive at the time of signing informed consent
3. Male subjects who are considered healthy by the investigator (or subinvestigator) based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs measurements and ECG. If any clinical abnormality is identified and/or a laboratory test value exceeds the site's standard value, subjects will be considered appropriate for the study only if the investigator judges the abnormality to be not clinically significant and not to increase the risk to the subject by participation in the study nor to compromise study endpoints
4. Male subjects whose body weight is = 50 kg and body mass index (BMI) is = 18.0 to = 32.0 kg/m2
5. Male subjects must agree to use appropriate contraception methods from the admission day (Day -1) until 3 months after discharge and agree not to donate sperm during this period
1. Subjects who regularly have < 1 bowel movement every 2 days
2. Subjects who have abnormal bowel habits such as diarrhoea, loose stools, or constipation within 2 weeks prior to the screening visit or prior to Day -1
3. Female subjects
4. Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionizing Radiation Regulations 1999, shall participate in the study
5. Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator at screening
6. Subjects with a history of any diseases of metabolism, liver, kidney, blood, lung, heart, stomach and intestines, urinary organs, endocrine system, nervous system, and mental illness, who have been judged to be ineligible for participation in this study by the investigator (or subinvestigator)
7. Subjects who need constant medication or have used any medication (including non-prescription drugs, vitamins, and dietary or herbal supplements) within 14 days before admission; exceptions may be permitted on a case by case basis if considered not to interfere with the aims of the study and agreed by the investigator and sponsor’s medical advisor
8. Subjects who have received strong CYP inducers (rifampicin, carbamazepine, phenytoin, enzalutamide, mitotane, and St John’s wort) and/or P-gp inducers (rifampicin, carbamazepine, phenytoin, tipranavir/ritonavir, and St John’s wort) within 28 days before admission
9. Subjects with the following laboratory abnormalities at screening:
9.1. Total bilirubin >1.2 × upper limit of normal (ULN)
9.2. Alanine aminotransferase (ALT) > 1.2 × ULN
9.3. Aspartate aminotransferase (AST) > 1.2 × ULN
9.4. Creatinine clearance < 60 mL/min/1.73m2
10. Subjects who have QTcF interval of > 450 msec at screening
11. Subjects whose resting systolic pressure is outside the range of 90-140 mmHg (aged 30-45 years) or 90-160 mmHg (aged 46 to 65 years), resting diastolic pressure is outside the range of 40-90 mmHg, or a pulse rate is outside the range of 40-90 beats per minute at screening
12. Subjects with a history of surgical resection of the stomach, vagus nerve, intestines, etc (excluding appendectomy)
13. Subjects with a history of clinically significant allergic symptoms, including food allergies (excluding allergic rhinitis presenting no symptoms at the time of screening)
14. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
15. Subjects who have a history or regular use of tobacco- or nicotine-containing products within 6 months before screening
16. Subjects with a history of drug and/or alcohol addiction within the past 2 years before screening or a positive test for drugs or alcohol at screening or admission visit
17. Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
18. Subjects with a positive result on any of the tests for the serologic detection of HI
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 1. Mass balance recovery after administration of a single 40-mg dose of carbon 14 labelled S-033188 ([14C] S 033188) as an oral suspension in the fasted state<br> 2. Whole blood and plasma concentrations of total radioactivity<br> 3. Metabolite profiling and structural identification from plasma, urine and faecal samples<br>
- Secondary Outcome Measures
Name Time Method <br> 1. Pharmacokinetics (PK) of the drug after administration of a single 40 mg dose of [14C]-S-033188 as an oral suspension in the fasted state<br> 2. Metabolites of S-033188 identified in plasma, urine, and faeces<br> 3. Safety and tolerability of S-033188 and S-033447 after administration of a single 40-mg dose of ([14C]-S-033188)<br>