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

Phase 1

Completed

• Conditions: Healthy Male Volunteers
• Interventions: Drug: [14C] SH-1028

• Registration Number: NCT04810533
• Lead Sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.

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.

Study Timeline

• Study Start: 2020-05-13
• Status Verified: 2021-03
• Primary Completion: 2021-03-05
• Study Completion: 2021-03-05
• Study First Submitted: 2021-03-17
• Study First Submitted QC: 2021-03-18
• Last Update Submitted: 2021-03-18
• Study First Posted: 2021-03-23
• Last Update Posted: 2021-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[14C] SH-1028	[14C] SH-1028	Volunteers will receive 200 mg \[14C\] SH-1028 containing a nominal 88 μCi activity, administered by mouth, as a solution.

Primary Outcome Measures

Name	Time	Method
The percentage of radioactive dose of [14C] radiolabelled SH-1028 recovered in urine, faeces and in total, up to Day 15.	Day1 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.
The concentrations of SH-1028, Imp2 and Imp3 in plasma up to Day 15	Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs	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.
Types of adverse events	Baseline (Day-2) to Day 15	Types of adverse events assessed by CTCAE v5.0 that occurred during the trial
The percentage of radioactive dose of [14C] radiolabelled SH-1028 recovered in blood and in total, up to Day 15	Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs	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.
Proportion of different metabolites	Blood samples : - 0.5hrs, 1hrs, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs, 168hrs, 216hrs, 264hrs and 336hrs	Proportion of different metabolites in healthy volunteers after oral administration of \[14C\]SH-1028

Trial Locations

Locations (1)

Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine; 🇨🇳 Nanjing, Jiangsu, China