Study Evaluating the Mass Balance And Biotransformation of Single Dose[14C] AST2818 in Chinese Healthy Male Volunteers

NCT03941340 | Completed Phase 1

• 1 other identifier: 20190130
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Study to Evaluate the Mass Balance and Biotransformation of Single Dose\[14C\] AST2818 in Chinese Healthy Male Volunteers

Conditions

Healthy Male Volunteers

Outcome Measures

Primary Outcomes (5)

• The distribution of AST2818 in the whole blood and plasma and whole radioactive pharmacokinetics following the single orally administered [14C]-AST2818 in healthy male volunteers.

  The percentage of radioactive dose of \[14C\] radiolabelled AST2818 recovered in blood and in total, up to Day 85（p.s:The administration time on the first day is 7:30 am）

  Blood samples (hrs) - 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, every 24 to 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 1848 and 2016.

• Quantitive analysis of whole radioactivity of excrement of orally administered [14C]-AST2818 in healthy volunteers to obtain the mass balance data and the main excretion pathway in human body.

  The percentage of radioactive dose of \[14C\] radiolabelled AST2818 recovered in urine, faeces and in total, up to Day 85（p.s:The administration time on the first day is 7:30 am）

  Urine and faeces (hrs): 0-4, 4-8, 8-12, 12-24, every 24 to 504, 624-672, 792-840, 960-1008, 1128-1176, 1296-1344, 1464-1512, 1632-1680, 1800-1848 and 1968-2016.

• Quantitive analysis of the concentrations of AST2818 and AST5902 (Metabolite of AST2818) in plasma using the validated LC-MS/MS to obtain pharmacokinetic data;

  The concentrations of AST2818 and AST5902 in plasma up to Day 85（p.s:The administration time on the first day is 7:30 am）

  Blood samples (hrs) - 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, every 24 to 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 1848 and 2016.

• Proportion of different metabolites in healthy volunteers after oral administration of [14C]-AST2818

  Proportion of different metabolites

  Blood samples (hrs) - 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, every 24 to 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 1848 and 2016.

• Types of adverse events assessed by CTCAE v5.0 that occurred during the trial

  Types of adverse events

  Baseline (Day-1) to Day 85（p.s:The administration time on the first day is 7:30 am）

Study Arms (1)

[14C]-AST2818 80mg (oral solution)

EXPERIMENTAL

Volunteers will receive 80 mg \[14C\]-AST2818 containing a nominal 100 μCi activity, administered by mouth, as a solution.

Drug: [14]-AST2818

Interventions

[14]-AST2818 DRUG

Volunteer will receive a single oral dose of 80 mg /100 u Ci \[14C\]-AST2818 as a solution on Day 1

[14C]-AST2818 80mg (oral solution)

Eligibility Criteria

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

You may qualify if:

• Healthy adult;
• Body weight: The body mass index varies in the range of 19 - 26 kg/m2 (including 19 and 26 kg/m2);
• Signing the informed consent forms by oneself ;
• Be able to communicate well with the researcher and be able to complete the trial in accordance with the program.

You may not qualify if:

• Those with abnormal examination and clinical significance ( including Physical examination, routine laboratory examination (blood routine, urine routine, fecal routine + Occult blood, blood biochemistry, blood coagulation routine, thyroid function), 12-lead electrocardiogram, X-ray (positive position), abdominal B-mode ultrasonography (liver, gallbladder, pancreas, spleen and kidney), etc)；
• Those with routine urine examination showed positive urinary protein；
• Those with QTcF \> 470 msec in resting state, corrected by ECG during screening period；
• Those with HBsAg , HBeAg and HCVAb were positive；
• Those with HIVAb was positive；
• Those with treponema pallidum Ab was positive；
• Those who take any drugs that inhibit or induce the CYP450 enzyme (i.e., inducers- barbiturates, tegretol, phenytoin, rifampicin, hexadecadrol, rifabutin, rifapentini; inhibitors- SSRI-antidepressant, cimetidine, diltiazem, macrolides, verapamil, imidazoles- antifungal drugs) 30 days prior to screening period；
• Those who take any drug, health care products (including vitamins), chinese traditional medicine 14 days prior to screening period；
• Those who participated other clinical trials or took the investigational drug 3 months prior to screening period, or prepare to take part in other clinical trials within 1 month after finishing this trial；
• Those who have history of organic heart disease, heart failure, myocardial infarction, angina, unexplained arrhythmia, torsional ventricular tachycardia, ventricular tachycardia and QT prolonged syndrome, or have the family history (Genetic proof or a close relative of sudden cardiac death at a young age) and symptom of QT prolonged syndrome ；
• Those who have severe disease of ophthalmic system, e.g., corneal, conjunctiva and eyelid diseases;
• Those who have undergone major surgery within the first 6 months of the screening period or have no complete surgical incision; major procedures include, but are not limited to, any operator with significant bleeding risk, prolonged general anesthesia, or incisional biopsy or significant traumatic injury;
• Those who have but not limited to circulatory system, endocrine system, nervous system, digestive system, urinary system, or have the history of blood, immunity spirit and metabolism diseases；
• Those who have allergic constitution, including being definitely allergic to TKIs or any ingredients of this trial drugs，any food materials or have special demands for foods，and cannot comply with the rule of unified diet；
• Those who have history of hand and foot syndrome；

Sponsors & Collaborators

• Allist Pharmaceuticals, Inc.: lead

Study Sites (1)

First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

Location

Study Officials

• LiYan Miu

  First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: May 7, 2019
• Study Start: April 8, 2019
• Primary Completion: September 6, 2019
• Study Completion: September 6, 2019
• Last Updated: January 6, 2020

Record last verified: 2020-01

Locations

CN (1)