Material Balance of [14C]Zorifertinib in Healthy Adult Male Participants in China
Phase I Clinical Study on Material Balance of [14C]Zorifertinib in Healthy Adult Male Participants in China
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: John Ge, M.D.
- Phone Number: +86 (0)21-63862197
- Email: john.ge@alphabiopharma.com.cn
Study Locations
-
-
Jiangsu
-
Suzhou, Jiangsu, China, 215000
- The First Affiliated Hospital of Soochow University
-
Contact:
- Liyan Miao, Ph.D.
- Phone Number: 18915505252
- Email: miaolysuzhou@163.com
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Healthy Chinese males;
- Age at the time of signing the informed consent form: 18-45 years (inclusive);
- Body mass index (BMI) ranging from 19-26 kg/m2 (inclusive), with a body weight of no less than 50 kg;
- Fully understand the purpose and requirements of this study and voluntarily sign the informed consent form;
- Be able to communicate well with the investigators and complete the trial according to the protocol.
- The 14C content in plasma and urine samples obtained during screening are within general environmental 14C background levels. Directly analyzed plasma samples must have values ≤150 pMC, and urine samples containing petroleum-based carbon carriers must have values ≤50 pMC.
Exclusion Criteria:
Ancillary Examinations:
- Abnormal findings from comprehensive physical examination, vital signs, laboratory tests (hematology, blood biochemistry, coagulation function, urinalysis, routine stool + occult blood, thyroid function), 12-lead ECG, chest X-ray (posteroanterior view), abdominal ultrasound, digital rectal examination, etc., that are judged by the investigator as clinically significant.
- Resting corrected QT interval (Fridericia correction, QTcF = QT/RR1/3) obtained from 12-lead ECG >450 ms in males, or other abnormalities judged by the investigator as clinically significant.
- Positive result for any of the following: hepatitis B surface antigen or hepatitis B e antigen, hepatitis C virus antibody, Treponema pallidum antibody, or human immunodeficiency virus antigen/antibody combination test (HIV-Ag/Ab).
Abnormal findings from ophthalmic examination (slit lamp, intraocular pressure, fundus photography) that are clinically significant.
Medication History:
- Use of any drugs that inhibit or induce the drug-metabolizing enzyme CYP3A4 within 30 days prior to the screening period.
Use of any prescription drugs, over-the-counter drugs, herbal medicines, or food supplements (e.g., vitamins, calcium supplements) within 14 days prior to the screening period.
Medical and Surgical History:
- History of any clinically serious disease or condition that the investigator believes may affect the trial results, including but not limited to circulatory, respiratory, endocrine, nervous, digestive, urinary, hematologic, immune, psychiatric, or metabolic diseases;
- History of dysphagia or any condition that may affect drug absorption, e.g., gastrectomy, cholecystectomy, gastric bypass, duodenotomy, colectomy, inflammatory bowel disease;
- History of organic heart disease, heart failure, myocardial infarction, angina pectoris, arrhythmia, ventricular tachycardia, clinically symptomatic AV block, long QT syndrome, or family history of long QT syndrome (evidenced by genetic proof or sudden cardiac death of a close relative at a young age);
- Major surgery within 6 months prior to the screening period, or surgical incision not fully healed; Major surgery includes, but is not limited to, any procedure with significant bleeding risk, prolonged general anesthesia, incisional biopsy, or significant traumatic injury;
- Allergic constitution, e.g., known history of allergy to two or more substances; Or judged by the investigator as potentially allergic to the investigational drug;
Hemorrhoids or perianal diseases with regular/ongoing hematochezia, irritable bowel syndrome, inflammatory bowel disease.
Lifestyle Habits:
- Habitual constipation or diarrhea;
- Alcoholism or regular alcohol consumption within 6 months prior to screening, i.e., alcohol intake exceeding 14 units per week (1 unit = 360 mL beer, or 45 mL spirit with 40% alcohol, or 150 mL wine), or a breath alcohol test result ≥20 mg/dL at screening, or inability to abstain from alcohol during the trial period;
- Smoking >5 cigarettes per day or habitual use of nicotine-containing products within 3 months prior to screening, or inability to abstain during the trial period;
- Drug abuse or use of soft drugs (e.g., cannabis) within 3 months prior to screening, or use of hard drugs (e.g., amphetamines, phencyclidine) within 1 year prior to screening; Or positive urine screen for drugs of abuse during the screening period;
Habitual consumption of grapefruit juice or excessive tea, coffee, and/or caffeinated beverages, and inability to abstain during the study period.
Others:
- Participation in a radiolabeled drug trial within 1 year prior to screening, or participation in a 14C-labeled breath test within 3 months prior to screening;
- History of needle phobia or blood phobia, difficulty with blood collection, or inability to tolerate venous puncture;
- Participation in any other clinical trial (including drug and device trials) within 3 months prior to the screening period;
- Vaccination within 1 month prior to screening, or planned vaccination during the study period;
- Plan to father a child or donate sperm during the study period or within 1 year after study completion, or disagreement to use strict contraceptive measures (see Appendix 1) for themselves and their partners during the study period and within 1 year after study completion;
- Blood loss or blood donation of ≥400 mL within 3 months prior to screening, or blood transfusion within 1 month;
- Any other factor that, in the investigator's opinion, makes the participant unsuitable for participation in this trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Single Dose Zorifertinib Group
|
Single oral administration of 200 mg/5 µCi [¹⁴C]Zorifertinib in healthy male subjects under fasting condition
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Total radioactive recovery and cumulative total radioactive recovery in urine and feces at each time interval
Time Frame: Pre-dose up to 312 hours after dosing, or until termination criteria met
|
Pre-dose up to 312 hours after dosing, or until termination criteria met
|
|
|
Percentage of total radioactivity exposure (%AUC), percentage of parent drug and its metabolites (%Dose), and metabolite identification
Time Frame: Pre-dose up to 312 hours after dosing, or until termination criteria met
|
Percentage of total radioactivity exposure (%AUC) accounted for by parent drug and its metabolites in plasma.
Percentage of administered dose (%Dose) accounted for by parent drug and its metabolites in urine and faeces.
Identification of metabolites in plasma, urine, and feces
|
Pre-dose up to 312 hours after dosing, or until termination criteria met
|
|
Peak Plasma Concentration (Cmax)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Time to Peak Concentration (Tmax)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Area under the plasma concentration versus time curve (AUC)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Elimination Half-Life (t1/2)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Terminal Rate Constant (λz)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Apparent Volume of Distribution (Vz/F)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Apparent Clearance (CLz/F)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Mean Residence Time (MRT)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Whole blood / plasma total radioactivity ratio
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Peak Plasma Concentration (Cmax)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Time to Peak Concentration (Tmax)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Area under the plasma concentration versus time curve (AUC)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Elimination Half-Life (t1/2)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Terminal Rate Constant (λz)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Apparent Volume of Distribution (Vz/F)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Apparent Clearance (CLz/F)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Mean Residence Time (MRT)
Time Frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
|
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
|
Pre-dose up to 120 hours after dosing,or until termination criteria met
|
|
Incidence and severity of Adverse Events (AEs)
Time Frame: Pre-dose up to 312 hours after dosing, or until termination criteria met
|
All adverse events were classified according to the CTCAE (version: 6.0)
|
Pre-dose up to 312 hours after dosing, or until termination criteria met
|
Collaborators and Investigators
Sponsor
Sponsor
Investigators
Investigators
- Principal Investigator: Liyan Miao, Ph.D., The First Affiliated Hospital of Soochow University
Study record dates
Study Major Dates
Study Start (Estimated)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- AZD3759-CIT-101
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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