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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukemia (CML)
• Intervention / Treatment: Drug: [14C] HQP1351

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

Contacts and Locations

Study Locations

• China
  • Nanjing, China
    • The First Affiliated Hospital with Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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] 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.	Drug: [14C] HQP1351; Orally, single dose of 30mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.
• Collaborators: HealthQuest Pharma Inc.
• Investigators: Principal Investigator: Feng Shao, Doctor, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2019
• Primary Completion (Actual): January 13, 2020
• Study Completion (Actual): January 13, 2020

Study Registration Dates

• First Submitted: October 11, 2019
• First Submitted That Met QC Criteria: October 11, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Chronic Myeloid Leukemia; HQP1351
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: HQP1351XC105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No