The Absorption, Metabolism and Excretion of [14C] HQP1351 in Humans

Study Overview
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Brief Summary
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The objective of this study is to determine the mass balance and routes of excretion of total radioactivity after a single oral 30mg (100µCi) dose of [14C] HQP1351 given as a suspension. For further clinical development, human mass balance data are required to elucidate the absorption, metabolism, and excretion of HQP1351.

Official Title
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A Single-center, Open-label, Single-dose Phase I Study to Investigate the Absorption, Metabolism and Excretion of [14C] HQP1351 After a Single Oral 30mg (100µCi) Dose in Healthy Chinese Male Subjects

Conditions
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Chronic Myeloid Leukemia (CML)

Intervention / Treatment
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* Drug: [14C] HQP1351


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A subject will be eligible for study participation if he meets the following criteria: Healthy male volunteers between the ages of 18 to 50 years old, inclusive; Body weight >=50 kg, Body mass index (body weight(kg)/hight2(m2)) between 19 and 26 kg/m2 (inclusive); Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or any abnormality that is non-clinically significant; 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 1 year after discontinuing treatment with the investigational product. Must understand, and voluntarily sign the informed consent, comply with the requirements of the study. Exclusion Criteria: A subject will not be eligible for study participation if he meets any of the exclusion criteria: History of or current clinically significant cardio, pulmonary, endocrine, metabolism, renal, hepatic, gastrointestinal, dermatology, infection, hematology, neurological, mental disease or disorder; Positive test for HBsAg, HBeAg, anti-HCV, anti-HIV or syphilis antibody; Abnormality in blood pressure, including hypertensive BP (SBP>=140 mmHg, or DBP >=90 mmHg), or hypotensive BP (SBP<90 mmHg, or DBP <=55 mmHg), Pulse rate<55 bpm or >100 bpm; Long-QT syndrome or family history of it, or QTcB interval > 450 ms; intraventricular blocks or left/right bundle branch block or QRS>120ms; frequent ventricular ectopic beats (any 10s ECG ventricular premature beat >= 1 in screening period); or abnormal resting heart rate (> 100 bpm) The following abnormal clinical laboratory values HGB < LLN or HGB>ULN, and is judged as clinically significant by the investigator； Abnormal ALB, TP, CRE, ALT, AST, BIL, BUN, GLU value, and is judged as clinically significant by the investigator; Received any drug within 14 days before taking the investigational drug, including any prescription drug, OTC drug, herbal drug or health care product with medicinal effect; Received any other investigating products or participated in any clinical trails three month before screening or within 10 t1/2 after receiving other investigating products; History of or current swallowing disorder, active gastrointestinal diseases, or other diseases that significantly affect absorption, distribution, metabolism and excretion of drugs; Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease or history of gastrointestinal surgery and cholecystectomy; Hemorrhoids or perianal disease with regular/perianal bleeding; Allergies, have allergies to two or more drugs or foods; or have known allergies to the components of the drug (microcrystalline cellulose, stearic acid, croscarmellose sodium); Have donated 400ml or more of blood or plasma 3 months prior to the study drug administration, or more than 50ml within 2 weeks prior to administration; Vaccination was administered within 6 months prior to screening or during screening; History of drug or alcohol abuse; Smoking (> 10 cigarette / day), drinking (> 15 g, pure alcohol / day, equivalent to 450 ml beer, 150 ml wine or 50 ml low-alcohol liquor), or abusing drugs within last 3 months; Subject with mentally ill and could not understand the property, scope and possible consequences of the study; subject in prison or whose freedom is restricted by administrative or legal issues; Failure to comply with clinical study protocols, such as non-cooperation, follow-up visit and completion of entire study; Abnormal coagulation function or known severe bleeding tendency; Subjects who have participated in radiolabeled clinical study prior to drug administration; 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). Investigators think that subjects are not suitable to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [14C] HQP1351<br>To investigate the absorption properties, as well as to evaluate the mass balance and elucidate the pathways of biotransformation after a single oral dose (30mg, 100µCi) of [14C] HQP1351 to healthy Chinese male subjects. | Drug: [14C] HQP1351<br>* Orally, single dose of 30mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radioactivity concentration of each blood and plasma sample | Use liquid scintillation counter to evaluate Radioactivity concentration of each blood and plasma sample | Day 1- Day 15 | 
| Radioactivity concentration of each urine samples | Use liquid scintillation counter to evaluate Radioactivity concentration of each urine sample | Day 1- Day 15 | 
| Radioactivity concentration of each feces samples | Use liquid scintillation counter to evaluate Radioactivity concentration of each feces sample | Day 1- Day 15 | 
| Total recovery of radioactivity in urine and feces | Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample | Day 1- Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma drug concentrations | To determine the plasma concentrations of HQP1351 with validated LC-MS/MS method for obtaining its pharmacokinetics parameters | Day 1- Day 15 | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | According to CTCAE v5.0, the number and frequency of adverse events after a single dose of test drug were assessed. | Day 1- Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Myeloid Leukemia, HQP1351