Clinical trial NCT04810533: The Absorption, Metabolism and Excretion of [14C]SH-1028 in Chinese Healthy Male Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Male Volunteers
Lead sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-03-23
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria:

1. Healthy male volunteers between the age of 18 to 50 years old；
2. Body weight \>=50 kg, Body mass index between 19 and 26 kg/m2 (including 19 and 26 kg/m2);
3. Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or any abnormality that is non-clinically significant;
4. 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.;
5. Signing the informed consent forms by oneself;
6. Be able to communicate well with the researcher and be able to complete the trial in accordance with the program.

Exclusion Criteria:

1. History of or current clinically significant cardio, pulmonary, endocrine, metabolism, renal, hepatic, gastrointestinal, dermatology, infection, hematology, neurological, mental disease or disorder;
2. Positive test for HBs-Ag, HCV-Ab, HIV-Ab, or syphilis antibody;
3. Long-QT syndrome or family history of it, or QTcF interval \> 450 mses;
4. Allergies, have allergies to drugs or foods; or have known allergies to the components of the drug;
5. Those who smoked daily \>5 sticks of cigarette 3 months prior to first dose or cannot give up smoking during study；
6. 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；
7. Those have history of drug abuse or taking soft drug (i.e., marihuana); or the results of urine test in drugs were positive;
8. Participated in other clinical trials within 3 months before screening;
9. Received any drug within 14 days before taking the investigational drug;
10. 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；
11. History of syncope / needle syncope and intolerable intravenous indwelling needle;
12. Those who have undergone major surgery within the first 6 months of the screening period;
13. Those who have habitual constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease；
14. Hemorrhoids or perianal disease with regular/perianal bleeding;
15. 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);
16. Those who cannot complete this study because of other reasons, or any factors judged by investigator that the participants cannot meet.

Primary outcomes:
measure: The percentage of radioactive dose of [14C] radiolabelled SH-1028 recovered in blood and in total, up to Day 15
timeFrame: Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs
measure: The percentage of radioactive dose of [14C] radiolabelled SH-1028 recovered in urine, faeces and in total, up to Day 15.
timeFrame: Day1 to Day 15
measure: The concentrations of SH-1028, Imp2 and Imp3 in plasma up to Day 15
timeFrame: Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs
measure: Proportion of different metabolites
timeFrame: Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs
measure: Types of adverse events
timeFrame: Baseline (Day-2) to Day 15
Secondary outcomes:
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
state: Jiangsu
Study officials:
affiliation: Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
name: Feng Shao, Ph D
role: PRINCIPAL_INVESTIGATOR
affiliation: Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
name: Wei Liu, M.A
role: PRINCIPAL_INVESTIGATOR
References: