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

Phase 1

Completed

• Conditions: Chronic Myeloid Leukemia (CML)
• Interventions: Drug: [14C] HQP1351

• Registration Number: NCT04126707
• Lead Sponsor: Ascentage Pharma Group Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-11
• Study First Submitted QC: 2019-10-11
• Study First Posted: 2019-10-15
• Study Start: 2019-11-19
• Primary Completion: 2020-01-13
• Study Completion: 2020-01-13
• Status Verified: 2020-07
• Last Update Submitted: 2021-09-07
• Last Update Posted: 2021-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

Inclusion Criteria

A subject will be eligible for study participation if he meets the following criteria:

1. Healthy male volunteers between the ages of 18 to 50 years old, inclusive;
2. Body weight >=50 kg, Body mass index (body weight(kg)/hight2(m2)) between 19 and 26 kg/m2 (inclusive);
3. Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or any abnormality that is non-clinically significant;
4. 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.
5. 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:

1. History of or current clinically significant cardio, pulmonary, endocrine, metabolism, renal, hepatic, gastrointestinal, dermatology, infection, hematology, neurological, mental disease or disorder;

2. Positive test for HBsAg, HBeAg, anti-HCV, anti-HIV or syphilis antibody;

3. 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;

4. 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)

5. The following abnormal clinical laboratory values

   1. HGB < LLN or HGB>ULN, and is judged as clinically significant by the investigator；
   2. Abnormal ALB, TP, CRE, ALT, AST, BIL, BUN, GLU value, and is judged as clinically significant by the investigator;

6. 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;

7. 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;

8. History of or current swallowing disorder, active gastrointestinal diseases, or other diseases that significantly affect absorption, distribution, metabolism and excretion of drugs;

9. Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease or history of gastrointestinal surgery and cholecystectomy;

10. Hemorrhoids or perianal disease with regular/perianal bleeding;

11. 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);

12. 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;

13. Vaccination was administered within 6 months prior to screening or during screening;

14. History of drug or alcohol abuse;

15. 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;

16. Subject with mentally ill and could not understand the property, scope and possible consequences of the study;

17. subject in prison or whose freedom is restricted by administrative or legal issues;

18. Failure to comply with clinical study protocols, such as non-cooperation, follow-up visit and completion of entire study;

19. Abnormal coagulation function or known severe bleeding tendency;

20. Subjects who have participated in radiolabeled clinical study prior to drug administration;

21. 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).

22. Investigators think that subjects are not suitable to participate in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[14C] HQP1351	[14C] HQP1351	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital with Nanjing Medical University; 🇨🇳 Nanjing, China