[14C] Study on Mass Balance and Biotransformation of STI-1558 in Healthy Chinese Adult Male Subjects

NCT05754411 | Completed Phase 1

• 1 other identifier: MPR-COV-103CN
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This trial adopts a single-center, single-dose, single-period, non-randomized, open-label study design. It is planned to enroll 6\~8 healthy male subjects, and each subject receives single oral administration of drug solution containing 600mg/approximately 100µCi \[14C\]STI-1558 under fasting conditions on trial D1. The whole blood, plasma, urine and stool samples are collected at specified time points/intervals during the trial. The pharmacokinetic parameters of the total radioactivity in plasma and whole blood, the material concentration ratios of the total radioactivity in plasma and whole blood, and the material balances are obtained by testing the total radioactivity of \[14C\]STI-1558 in plasma, whole blood, urine and feces. Meanwhile, using isotope tracer and mass spectrometry techniques, the main pathways and characteristics of metabolism and elimination of STI-1558 in humans are obtained through the quantification of radioactive metabolite profiles and the structure identification of the main metabolites in plasma, urine and feces of the subjects. The entire duration of trial is expected to be 5 months.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (8)

• Distribution Ratio of the Total Radioactivity in Whole Blood and in Plasma.

  To investigate the distribution ratio of the total radioactivity in whole blood and plasma after oral administration of \[14C\]STI-1558 in healthy subjects。

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Total Radioactivity in Whole Blood and in Plasma:AUC[0-t].

  To investigate the pharmacokinetic profiles of the total radioactivity in whole blood and plasma after oral administration of \[14C\]STI-1558 in healthy subjects.

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Total Radioactivity in Whole Blood and in Plasma:Cmax .

  To investigate the pharmacokinetic profiles of the total radioactivity in whole blood and plasma after oral administration of \[14C\]STI-1558 in healthy subjects。

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Total Radioactivity in Whole Blood and in Plasma:AUC[0-inf].

  To investigate the pharmacokinetic profiles of the total radioactivity in whole blood and plasma after oral administration of \[14C\]STI-1558 in healthy subjects。

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration

• Total Radioactivity in Whole Blood and in Plasma:Tmax.

  To investigate the pharmacokinetic profiles of the total radioactivity in whole blood and plasma after oral administration of \[14C\]STI-1558 in healthy subjects。

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Total Radioactivity in Whole Blood and in Plasma:t1/2.

  To investigate the pharmacokinetic profiles of the total radioactivity in whole blood and plasma after oral administration of \[14C\]STI-1558 in healthy subjects。

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Total Radioactivity in the Excreta(Urine).

  To perform the quantitative analysis of the total radioactivity in urine, and obtain the recovery of radioactivity and the main excretion pathways in humans after oral administration of \[14C\]STI-1558 in healthy subjects.

  Urine samples collected:-24~0 hours before administration of [14C]STI-1558 and 0~8,8~24,24~48,48~72,72~96,96~120,120~144,144~168,168~192,192~216,216~240,240~264,264~288,288~312, 312~336 hours after administration.

• Total Radioactivity in the Excreta(Faeces).

  To perform the quantitative analysis of the total radioactivity in faeces, and obtain the recovery of radioactivity and the main excretion pathways in humans after oral administration of \[14C\]STI-1558 in healthy subjects.

  Faeces samples collected:-48~0 hours before administration of [14C]STI-1558 and 0~24,24~48,48~72, 72~96,96~120,120~144,144~168,168~192,192~216, 216~240,240~264,264~288,288~312 ,312~336 hours after administration.

Secondary Outcomes (11)

• Plasma Concentrations of STI-1558 (active compound AC1115):AUC[0-t].

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Plasma Concentrations of STI-1558 (active compound AC1115):AUC[0-inf].

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Plasma Concentrations of STI-1558 (active compound AC1115):Cmax.

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Plasma Concentrations of STI-1558 (active compound AC1115):Tmax .

  Blood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

• Plasma Concentrations of STI-1558 (active compound AC1115):t1/2 .

  TBlood samples collected:Within 1hour before administration of [14C]STI-1558 and 0.25、0.5、1、1.5、2、 3、4、6、8、12、24、48、72、120 、168 hours after administration.

Study Arms (1)

[14C]STI-1558

EXPERIMENTAL

Drug: [14C]STI-1558

Interventions

[14C]STI-1558 DRUG

Fasting oral administration of 600 mg \[ 14C \] STI-1558 ( about 100 μCi ) solution.

[14C]STI-1558

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing to sign informed consent form;
• Chinese healthy male subjects between 18-45 years of age (inclusive);
• Weight: weight ≥ 50.0kg and body mass index (BMI) between 19.0\~26.0kg/m2 (inclusive);
• Male subjects of childbearing potential who have no birth plans throughout the study period and for 12 months after the end of study, and agree to take contraceptive measures with their sexual partners during this period, such as condoms, contraceptive sponges, contraceptive gels, contraceptive films, intrauterine devices, oral or injected contraceptives (only suitable for the period after end of trial), subcutaneous implants (only suitable for the period after end of trial) or other contraceptive measures;
• Able to communicate well with the investigator and able to complete the trial in accordance with the protocol.

You may not qualify if:

• Laboratory tests:
• Subjects who have clinically significant abnormalities through comprehensive physical examinations, vital signs, routine laboratory tests (blood routine, blood biochemistry, 4-item coagulation function, urine routine, stool routine + occult blood, etc.) and 12-lead ECG;
• Thyroid-stimulating hormone (TSH) \> ULN (upper limit of normal); or free triiodothyronine (FT3) \> ULN; or free thyroxine (FT4) \> ULN;
• Blood amylase or lipase \> ULN;
• Subjects who have any positive tests for hepatitis B surface antigen, hepatitis C antibody, treponema pallidum antibody, or combined HIV antigen/antibody test (primary screening);
• Medication history:
• Subjects who have received any investigational products (including marketed products) or participated in any clinical trials with drugs/devices within 3 months prior to screening;
• Subjects who have used any drugs that inhibit or induce liver drug metabolizing enzymes within 30 days prior to screening (such as: inducers - barbiturates, carbamazepine, phenytoin, rifampicin, dexamethasone, rifabutin, rifapentine, etc.; inhibitors - SSRI antidepressants, cimetidine, diltiazem, macrolides, verapamil, imidazole antifungals, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines, etc.);
• Subjects who have taken any drugs that inhibit gastric acid secretion and gastric antiacids within 14 days prior to screening, such as H2 receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine, roxatidine, etc.); proton pump inhibitors (omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole, etc.); and cholinergic receptor blockers (atropine, pirenzepine, etc.);
• Medical history and surgery history:
• Subjects with any history of clinically significant diseases or diseases or conditions that may affect the trial results in opinion of the investigator, including but not limited to history of motor system, nervous system, endocrine system, circulatory system, respiratory system, digestive system, urinary system and reproductive system diseases;
• Subjects with previous history of organic heart diseases (such as history of heart failure, history of myocardial infarction, history of angina pectoris), history of unexplained arrhythmia (such as history of ventricular tachycardia, history of QT prolongation syndrome) or symptoms or family history (with genetic evidences or close relatives who died suddenly from cardiac causes at a young age) of QT prolongation syndrome;
• Subjects with coagulation disorders, hemorrhagic diseases (such as hemophilia, purpura) or hemorrhagic symptoms (such as hematemesis, melena, hemorrhage of gastrointestinal tract, serious or recurrent epistaxis, hemoptysis, obvious hematuria or intracranial hemorrhage);
• Subjects who have suffered esophageal reflux or peptic ulcer diseases, or have received any previous surgical operations that may affect drug absorption (such as cholecystectomy) within 3 months prior to screening;
• Subjects with significant allergic conditions, including subjects who are clearly allergic to two or more other drugs or food ingredients; or subjects with previous history or family history of allergic skin diseases; or subjects who have special dietary requirements and cannot follow a unified diet;

Sponsors & Collaborators

• Zhejiang ACEA Pharmaceutical Co. Ltd.: lead

Study Sites (1)

Beijing Gaobo Boren Hospital

Beijing, China

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2023
• First Posted: March 3, 2023
• Study Start: May 15, 2023
• Primary Completion: June 22, 2023
• Study Completion: November 9, 2023
• Last Updated: December 7, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)