Study on Mass Balance of [14C]HSK39297 in Healthy Chinese Adult Male Subjects

To evaluate the absorption, metabolism and excretion in healthy Chinese male subjects after a single oral dose of [14C]HSK39297

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: Carbon-14 labeled HSK39297

Detailed Description

1. To quantitatively analyze the total radioactivity in excreta after oral administration of [14C]HHSK39297 in healthy subjects, obtain the data on human radioactivity excretion rate and determine the main excretion pathways
2. To quantitatively analyze the total radioactivity in whole blood and plasma in healthy subjects after oral administration of [14C]HSK39297, to obtain the pharmacokinetics of total radioactivity in plasma and to investigate the distribution of total radioactivity in whole blood and plasma
3. To obtain the radioactive metabolite profile in plasma, urine, and feces after oral administration of [14C]HSK39297 in healthy subjects, to identify the main metabolites and to determine the metabolism and elimination pathways

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China
      • The Second Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Chinese healthy male subjects aged between 18 and 45 years old (inclusive, at the time of signing the informed consent form);
2. Body weight ≥ 50 kg and body mass index (BMI) within the range of 19 - 26 kg/m² (inclusive);
3. Capable of comprehending the procedures and methodologies of this study, disposed to strictly adhere to the related requirements of the protocol, and capable of signing the informed consent form.

Exclusion Criteria:

1. Abnormal and clinically significant findings in physical examination, vital signs, laboratory tests (blood routine, biochemistry, coagulation function, urine routine, stool routine + fecal occult blood, thyroid function), ophthalmic examination (slit lamp, intraocular pressure, fundus photography), 12 - lead electrocardiogram [QT interval corrected by Fridericia method (QTcF), 350 - 450 ms (inclusive) for men], X - ray chest film (anterior - posterior and lateral views), abdominal B - ultrasound (liver, gallbladder, pancreas, spleen), urinary system B - ultrasound (kidneys, ureters, bladder, prostate), etc.
2. Positive for hepatitis B surface antigen, hepatitis C virus IgG antibody, human immunodeficiency virus antibody and antigen p24, and Treponema pallidum antibody.
3. Use of prescription drugs, over - the - counter drugs, or health care products, including Chinese patent medicine, within 14 days before the screening period or within 5 half - lives of the drug (whichever is longer).
4. Participated in a clinical trial and received investigational drugs or devices within 3 months before screening.
5. Use of any drugs that inhibit or induce the activity of liver drug - metabolizing enzymes or P - gp inhibitors within 30 days before screening.
6. Dysphagia or any conditions that may affect drug absorption (e.g., gastrectomy, cholecystectomy, gastric bypass, duodenotomy, colectomy).
7. Habitual constipation/diarrhea (feces collection required), history of malabsorption syndrome, or severe GI symptoms within 1 week before screening.
8. History of serious diseases in cardiovascular, digestive, etc. systems or other diseases/physiological conditions interfering with trial results.
9. History of organic heart disease, heart failure, myocardial infarction, angina pectoris, unexplained arrhythmia, torsades de pointes, ventricular tachycardia, atrioventricular block, QT prolongation syndrome, or having symptoms of QT prolongation syndrome and a family history (indicated by genetic evidence or sudden cardiac death of close relatives at a young age).
10. History of capsular bacterial infection (e.g., Neisseria meningitidis, etc.) within 6 months before screening.
11. History of tuberculosis infection or currently suffering from tuberculosis.
12. Underwent major surgery within 6 months before screening or surgical incision not healed (excluding healed appendicitis and rectal prolapse surgeries).
13. Severely allergic, allergic to trial drugs/excipients, two or more other drugs/foods, or having special diet requirements and unable to follow a unified diet.
14. Having hemorrhoids or perianal diseases with regular/ongoing rectal bleeding, irritable bowel syndrome, or inflammatory bowel disease.
15. Alcoholism or regular drinking (> 14 alcohol units/week) within 6 months before screening, or positive alcohol breath test.
16. Smoking more than 5 cigarettes per day or habitually using nicotine - containing products within 3 months before the screening period and being unable to quit during the trial.
17. Having drug abuse or dependence, with a positive urine drug abuse screening.
18. Habitually drinking grapefruit juice or excessive tea (more than 8 cups a day, 1 cup = 250 mL), or excessive caffeine intake (more than 3 cups of coffee a day, etc.) and being unable to quit during the trial.
19. Long - term exposure to radiation at work, or significant radiation exposure (≥ 2 chest/abd CT or ≥ 3 other X - rays) within 1 year before the trial, or participated in a radiopharmaceutical trial within 1 year.
20. Received a live vaccine within 1 month before screening or planned to during the trial.
21. History of fainting at the sight of needles/blood, difficult blood collection, or intolerance to venipuncture.
22. Fertility plan during the trial and within 1 year after the last dose, or disagreed to take strict contraceptive measures.
23. Blood loss or donation ≥ 400 mL within 3 months before screening, or received a blood transfusion within 1 month.
24. For any reason subject is considered by the investigator to be an unsuitable candidate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]HSK39297	Drug: Carbon-14 labeled HSK39297; Dose A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of total radioactivity in urine and fecal samples	Mass balance recovery of total radioactivity in urine and fecal samples	Up to 312 hours post dose
Total radioactivity in plasma PK	PK parameters of total radioactivity in the plasma; Ratio of total radioactivity concentration in whole blood/plasma at different time points.	Up to 312 hours post dose.
Percentage of radioactivity and identification of metabolites in plasma, urine and fecal samples	Percentage of prototype drugs and its metabolites in plasma, urine and fecal samples. Identification of the major metabolites	Up to 312 hours post dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	All subjects will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms and ophthalmological assessments	Up to 312 hours post dose.

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2024
• Primary Completion (Actual): September 27, 2024
• Study Completion (Actual): December 10, 2024

Study Registration Dates

• First Submitted: February 24, 2025
• First Submitted That Met QC Criteria: February 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Urological Manifestations; Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Proteinuria; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: HSK39297-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No