The Absorption, Metabolism and Excretion of [14C]SH-1028 in Chinese Healthy Male Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a single-center, open-label, single-dose phase I study to investigate the absorption, metabolism and excretion of [14C] SH-1028 in healthy Chinese male subjects. The study will be conducted into two steps：Firstly, 2 subjects are enrolled in to participate in the pilot study to grope for the collection time of plasma, urine and feces sampling post-dose. Then, the collection time of blood and excreta samples (urine and feces) from the subsequent 2-4 subjects will be adjusted according to the pilot study.

Detailed Description
-----------------
Subjects who had signed informed consent and meet inclusion criteria and no exclusion criteria are admitted to Phase I Clinical Unit two days prior to dosing (D-2). On the morning of Day 1 before dosing, subjects will be transferred to nuclear medical ward. And after an overnight fast of at least 10 h, subjects will receive a single oral dose of 200 mg (88 μCi) of [14C]SH-1028 as an oral suspension. Then, after two days of the dosing, subjects will be transferred back to Phase I Clinical Unit ward and confined to this unit until blood or excreta sampling and safety monitoring at the designated time points or intervals are complete.

Official Title
-----------------
A Single-center, Open-label, Single-dose Phase I Study to Investigate the Absorption, Metabolism and Excretion of [14C]SH-1028 in Chinese Healthy Male Subjects

Conditions
-----------------
Healthy Male Volunteers

Intervention / Treatment
-----------------
* Drug: [14C] SH-1028


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male volunteers between the age of 18 to 50 years old； Body weight >=50 kg, Body mass index between 19 and 26 kg/m2 (including 19 and 26 kg/m2); Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or any abnormality that is non-clinically significant; Male subjects of reproductive potential with partners will be instructed to, and must be willing to practice a highly effective method of birth control for the duration of the study and continuing 6 months after discontinuing treatment with the investigational product.; Signing the informed consent forms by oneself; Be able to communicate well with the researcher and be able to complete the trial in accordance with the program. Exclusion Criteria: History of or current clinically significant cardio, pulmonary, endocrine, metabolism, renal, hepatic, gastrointestinal, dermatology, infection, hematology, neurological, mental disease or disorder; Positive test for HBs-Ag, HCV-Ab, HIV-Ab, or syphilis antibody; Long-QT syndrome or family history of it, or QTcF interval > 450 mses; Allergies, have allergies to drugs or foods; or have known allergies to the components of the drug; Those who smoked daily >5 sticks of cigarette 3 months prior to first dose or cannot give up smoking during study； The weekly alcohol consumption was higher than 14 units of alcohol (1 unit=10ml or 8g absolute alcohol. 25 ml 40% liquor, 330ml 5% beers, 175ml 12% grape wine are equal to 1.0, 1.5 and 2.0 units of alcohol respectively) 3 months prior to screening period, or positive test for the alcohol breath test results during screening period； Those have history of drug abuse or taking soft drug (i.e., marihuana); or the results of urine test in drugs were positive; Participated in other clinical trials within 3 months before screening; Received any drug within 14 days before taking the investigational drug; Received any drugs that inhibit or induce the CYP450 enzyme (i.e., inducers- barbiturates, tegretol, phenytoin, rifampicin, hexadecadrol, rifabutin, rifapentini; inhibitors- SSRI-antidepressant, cimetidine, diltiazem, macrolides, verapamil, imidazoles- antifungal drugs) 30 days prior to screening period； History of syncope / needle syncope and intolerable intravenous indwelling needle; Those who have undergone major surgery within the first 6 months of the screening period; Those who have habitual constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease； Hemorrhoids or perianal disease with regular/perianal bleeding; Significant radiation exposure within one year prior to drug administration (more than one exposure from chest X-ray, CT scan, or barium meal examination and radiation-related occupations); Those who cannot complete this study because of other reasons, or any factors judged by investigator that the participants cannot meet.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [14C] SH-1028<br>Volunteers will receive 200 mg [14C] SH-1028 containing a nominal 88 μCi activity, administered by mouth, as a solution. | Drug: [14C] SH-1028<br>* Volunteer will receive a single oral dose of 200 mg/88 uCi [14C]SH-1028 as a solution on Day 1<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of radioactive dose of [14C] radiolabelled SH-1028 recovered in blood and in total, up to Day 15 | The distribution of [14C]SH-1028 in the whole blood and plasma and whole radioactive pharmacokinetics following the single orally administered [14C]SH-1028 in healthy male volunteers. | Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs | 
| The percentage of radioactive dose of [14C] radiolabelled SH-1028 recovered in urine, faeces and in total, up to Day 15. | Quantitive analysis of whole radioactivity of excrement of orally administered [14C]SH-1028 in healthy volunteers to obtain the mass balance data and the main excretion pathway in human body. | Day1 to Day 15 | 
| The concentrations of SH-1028, Imp2 and Imp3 in plasma up to Day 15 | Quantitive analysis of the concentrations of SH-1028 and Imp2,Imp3 (Metabolites of SH-1028) in plasma using the validated LC-MS/MS to obtain pharmacokinetic data. | Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs | 
| Proportion of different metabolites | Proportion of different metabolites in healthy volunteers after oral administration of [14C]SH-1028 | Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs | 
| Types of adverse events | Types of adverse events assessed by CTCAE v5.0 that occurred during the trial | Baseline (Day-2) to Day 15 |