Study on Mass Balance of [14C]HMPL-306（Isocitrate Dehydrogenase Inhibitor） in Healthy Chinese Adult Male Subjects

A Single-center, Open-label, Single-dose Phase I Clinical Study to Investigate the Human Mass Balance in Healthy Chinese Adult Male Subjects Following a Single Oral Dose of 250 mg/100 µCi [14C] HMPL-306

To evaluate the absorption, metabolism and excretion in healthy Chinese male subjects after a single oral dose of [14C]HMPL-306

Study Overview

• Status: Completed
• Conditions: Mass Balance Study
• Intervention / Treatment: Drug: 100 µCi [14C] HMPL-306

Detailed Description

• To quantitatively analyze the total radioactivity in excreta after oral administration of [14C]HMPL-306 in healthy subjects, obtain the data on human radioactivity excretion rate and determine the main excretion pathways;
• To obtain the radioactive metabolite profile in plasma, urine, and feces after oral administration of [14C]HMPL-306 in healthy subjects, to identify the main metabolites and to determine the metabolism and elimination pathways;
• To quantitatively analyze the total radioactivity in whole blood and plasma in healthy subjects after oral administration of [14C]HMPL-306, to obtain the pharmacokinetics of total radioactivity in plasma and to investigate the distribution of total radioactivity in whole blood and plasma;

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jinan, China
    • The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects are fully informed about the contents, procedures and possible adverse reactions of the study, voluntarily sign the informed consent form, and are able to communicate well with investigators and to complete all study procedures specified in the protocol;
2. Healthy male subjects who are 18 to 45 years (inclusive) at the time of signing the informed consent form.;
3. Weight ≥50 kg, and body mass index (BMI) between 19 - 26 kg/m2 (inclusive);
4. Subjects must promise to have no pregnancy plan or sperm donation plan and to use condoms during sexual intercourse from signing the informed consent form until 180 days after end of the study treatment. If the sexual partner is a female of childbearing potential, a highly effective method of contraception should be also used (see Appendix 1 for more information).

Exclusion Criteria:

1. History of serious allergy (e.g., drug allergy) and acute allergic rhinitis or food allergy within two weeks prior to screening;
2. Subjects with a history or clinical manifestation of clinically significant metabolic/endocrine, hepatic, renal, hematologic, pulmonary, immunologic, cardiovascular, gastrointestinal, genitourinary, neurologic, or psychiatric diseases within 3 months prior to and during the screening period (judged by investigators);
3. Previous history of hypertension;
4. Subjects who are positive for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibody, anti-human immunodeficiency virus (HIV) antibody, or anti-treponema pallidum antibody;
5. Smoking more than 10 cigarettes daily within 3 months prior to the screening and inability to refrain from smoking completely during the study period;
6. Regular alcohol consumption within 6 months prior to the study, i.e., drinking more than 14 units of alcohol per week (1 unit =360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine), or positive alcohol breath at screening;
7. Presence of drug abuse or dependence, or positive urine screen for drugs of abuse;
8. Subjects who have poor venous access, and have a fear of needles, hemophobia or difficulty in blood collection;
9. Having participated in clinical trials for other drugs within 3 months prior to the screening;
10. Workers who need to be exposed to radioactive condition for a long term; or those who have significant radiation exposure (≥2 times of chest/abdominal computerised tomography (CT), or ≥3 times of other kinds of X-ray examinations) within 1 year prior to administration, or have participated in the radiopharmaceutical labeling study;
11. Subjects who have been vaccinated within 30 days prior to administration and who have a plan for vaccination within 2 weeks after administration;
12. According to the investigator's judgment, the subjects have any other disease or status that may affect the normal completion of the study or the evaluation of the study data, or have any other condition that is not suitable for the study.

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: 100 µCi [14C] HMPL-306; After an overnight fasting of at least 10 hours, subjects will receive [14C] HMPL-306 containing 250 mg HMPL-306 (approximately 100 μCi radioactivity) 30 minutes after start of breakfast (must be completed within 30 minutes) and ensure that all of the drug is taken within 10 minutes.	Drug: 100 µCi [14C] HMPL-306; D1: 250 mg/100 µCi [14C] HMPL-306 Single dose; Other Names: 100 µCi [14C] HMPL-306 suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Human Mass Balance	Recovery and cumulative recovery of total radioactivity in excreta (urine and feces).	Day1~Day29
Human Mass Balance	Percentage of the unchanged drug and its metabolites in plasma to total radioactivity exposure levels in plasma;	Day-1~Day29
Human Mass Balance	Percentage of the unchanged drug and its metabolites in urine and feces to the administered dose;	Day-1~Day29
Human Mass Balance	Identification of major metabolites in plasma, urine and feces.	Day-1~Day29
Human Mass Balance	PK parameters of total radioactivity in the plasma; Ratio of total radioactivity concentration in whole blood/plasma at different time points.	Day-1~Day29

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Principal Investigator: Wei Zhao, offices director, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital)

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2024
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): July 2, 2025

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2024-306-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

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