A Mass Balance Study of [14C]ABSK021

NCT06186583 | Completed Phase 1

• 1 other identifier: ABSK021-104
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-site, open-label, single-cohort, single-dose study to assess the absorption, metabolism, and excretion profile of \[14C\] ABSK021 in healthy adult male subjects. The study plans to enroll 6 to 10 healthy male subjects to ensure at least 6 evaluable subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (5)

• Cumulative excretion rate of radioactivity in excreta (urine, feces) and total radioactivity (urine and feces)

  To assess the routes and rates of elimination of ABSK021 and its metabolites after single oral administration of \[14C\]ABSK021 in healthy adult male subjects

  All excreted urine and feces samples at specified time points during 0-504 hours after dosing will be collected.

• Percentage of each metabolite in urine and feces relative to the administered dose (% administered dose), or percentage of metabolites in plasma relative to total exposure AUC (% AUC);

  To determine the metabolism and elimination pathways of ABSK021 after single oral administration of \[14C\] ABSK021 in healthy adult male subjects, and identify major metabolites.All excreted urine and feces samples at specified time points during 0-504 hours after dosing will be collected.

  Conduct testing within 1 month after all subjects collect plasma, urine, and fecal samplesat all time points required by the protocol

• Identification of major metabolites in plasma, urine, and fecal samples

  To determine the metabolism and elimination pathways of ABSK021 after single oral administration of \[14C\] ABSK021 in healthy adult male subjects, and identify major metabolites.All excreted urine and feces and plasma samples at specified time points during 0-504 hours after dosing will be collected.

  Conduct testing within 1 month after all subjects collect plasma, urine, and fecal samplesat all time points required by the protocol

• AUC 0-∞

  To evaluate the pharmacokinetics of ABSK021 and its major metabolites in the urine of healthy adult male subjects after a single oral administration \[14C\] of ABSK021.

  Conduct testing within 1 month after all subjects collect all samples at all time points required by the protocol

• Tmax

  To evaluate the pharmacokinetics of ABSK021 and its major metabolites in the fecal of healthy adult male subjects after a single oral administration \[14C\] of ABSK021

  Conduct testing within 1 month after all subjects collect PK samples at all time points required by the protocol

Secondary Outcomes (1)

• Frequency, type and severity of adverse events/serious adverse events; changes in vital signs, 12-lead ECGs, laboratory tests, etc.

  From signing the ICF until 22 days after the first dosing

Study Arms (1)

[14C]ABSK021 Suspension

EXPERIMENTAL

On Day 1, subjects will receive a single oral dose of approximately 50 mg ABSK021 containing approximately 100 μCi of \[14C\] ABSK021 in the fasted state.

Drug: Pimicotinib（ABSK021）

Interventions

Pimicotinib（ABSK021） DRUG

A standard meal should be given to the subjects in the evening before dosing. Then, the subjects should fast for at least 10 hours. Water is not prohibited overnight. The next morning, the subjects should administer study drug in fasted state with warm water. The total volume of warm water and suspension is approximately 240 mL. Water is prohibited from 1 hour before dosing to 1 hour after dosing. No food is allowed within 4 hours after dosing. During the study, subjects will receive standardized meals at approximately the same time each day.

[14C]ABSK021 Suspension

Eligibility Criteria

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

You may qualify if:

• Subjects who fully understand the content, procedures and possible adverse reactions before the study, and voluntarily sign the informed consent form, and can complete the study in accordance with the requirements in the protocol;
• Healthy male subjects aged 18 to 45 years (including 18 and 45 years) at screening;
• Weight ≥ 50 kg, body mass index (BMI) between 19 and 28 (including 19 and 28), BMI = weight (kg)/height (m) 2;
• Subjects must have regular defecation in the past three months;
• Male subjects of childbearing potential must agree to use effective contraceptive methods during the study and within 12 months after administration of study drug . Male subjects must agree to not donate sperm during this period.

You may not qualify if:

• Abnormal and clinically significant complete physical examination, vital signs, digital rectal examination, laboratory tests (hematology, blood biochemistry, urinalysis, coagulation function, stool routine + occult blood, thyroid function, etc.), 12-lead electrocardiogram, chest X-ray (anteroposterior position), abdominal B ultrasound (hepatobiliary, pancreas, spleen and kidney);
• Abnormal and clinically significant ophthalmic examination (slit lamp, intraocular pressure and fundus photography);
• Tested positive for any one of the following: serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen/antibody, treponema pallidum antibody (Syphilis) screening;
• The baseline of heart rate corrected QT, QTcF interval prolongs \> 450ms; family history of long QT syndrome (Note: QTc interval is corrected by Fridericia formula);
• Creatinine clearance (CrCL) ≤ 60 mL/min, calculated using the Cockcroft-Gault formula ;
• Subjects with a history of cardiovascular, respiratory, blood, liver, kidney, gastrointestinal, endocrine or nervous system diseases, for whom the absorption, metabolism or elimination of the drug are significantly affected, or for whom the investigator judges that the disease(s) may pose a risk when taking the test drug, interfere with the interpretation of the data, or affect the ability of the subjects to participate in the study;
• Known or persistent mental disorders that may interfere with the subject's participation in the study, as judged by the investigator;
• Known history of allergy to any drug or food;
• Subjects who have participated in drug trials within 3 months before dosing.
• Subjects who have participated in this study or any other study related to ABSK021, and have previously exposed to ABSK021;
• Subjects who have used OATP1B1 inhibitors or strong CYP3A4 inhibitors or inducers (including grapefruit juice, grapefruit hybrids, pomegranates, carambola, grapefruit, Seville oranges and juice or other processed products) within 14 days prior to dosing;
• Subjects with factors that significantly affect drug absorption, distribution, metabolism and excretion, such as inability to take the test drug orally, obvious nausea and vomiting and malabsorption; Subjects with history of gastric or intestinal surgery or resection (appendectomy and hernia repair surgery is allowed);
• Subjects who are unwilling to comply with the dietary requirements/restrictions during the study. The specific dietary requirements are: (i) only eat the meals provided by the study sites during hospitalization, (ii) avoid consumption of OATP1B1 inhibitors or strong CYP3A4 inhibitors or inducers during this study;
• Subject whose weekly alcohol consumption is greater than 14 units (1 unit of alcohol is equivalent to approximately 360 mL beer, 45 mL of spirits with 40% alcohol or 150 mL wine) within 3 months before dosing, or whose alcohol breath test result is ≥ 20 mg/dl;
• Subjects who smoke more than 5 cigarettes per day (or an equivalent amount of tobacco or nicotine) within 3 months prior to dosing;

Sponsors & Collaborators

• Abbisko Therapeutics Co, Ltd: lead

Study Sites (1)

The First Affiliated Hospital of SOOCHOW UNIVERSITY

Suzhou, Jiangsu, 215000, China

Location

Study Officials

• Liyan Miao, Professor

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: On Day 1, subjects will receive a single oral dose of approximately 50 mg ABSK021 containing approximately 100 μCi of \[14C\] ABSK021 in the fasted state.

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: January 2, 2024
• Study Start: December 13, 2023
• Primary Completion: May 30, 2024
• Study Completion: July 30, 2024
• Last Updated: August 12, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)