The Absorption, Metabolism and Excretion of [14C]Ensartinib in Human

NCT03804541 | Unknown Phase 1 FDA Drug

• 1 other identifier: BTP-44316
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, single-dose phase I study to investigate the absorption, metabolism and excretion of \[14C\] Ensartinib in healthy Chinese male subjects. The study will be conducted into two steps：Firstly, 2 subjects are enrolled in to participate in the pilot study to grope for the completion date of plasma, urine and feces sampling on the 3rd day post-dose and onwards. Then, the collection time of blood and excreta samples (urine and feces) from the subsequent 4-6 subjects will be adjusted according to the pilot study.

Conditions

ALK-POSITIVE NSCLC

Outcome Measures

Primary Outcomes (4)

• Radioactivity concentration of each plasma sample

  Use liquid scintillation counter to evaluate Radioactivity concentration of each plasma（DPM/ml) sample

  Day1-Day15

• Radioactivity concentration of each urine samples

  Use liquid scintillation counter to evaluate Radioactivity concentration of each urine（DPM/ml） sample

  Day1-Day15

• Radioactivity concentration of each feces sample

  Use liquid scintillation counter to evaluate Radioactivity concentration of each feces（DPM/g） sample

  Day1-Day15

• Total recovery of radioactivity in urine and feces

  Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample.

  Day1-Day15

Secondary Outcomes (2)

• Plasma drug concentrations

  Day1-Day15

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  Day1-Day15

Study Arms (1)

[14C]Ensartinib

EXPERIMENTAL

To investigate the absorption properties, as well as to evaluate the mass balance and elucidate the pathways of biotransformation after a single oral dose (200mg, 100µCi) of \[14C\]Ensartinib to healthy Chinese male subjects。

Drug: Ensartinib

Interventions

Ensartinib DRUG

A novel, potent ALK inhibitor.The ALK inhibitor ensartinib has been validated in potency and selectivity assays indicating that it is more selective and up to 10 times more potent than competitive ALK inhibitors. Ensartinib has been active in animal models of non-small cell lung cancer (NSCLC) and neuroblastoma, a childhood cancer. Importantly, ensartinib has shown activity in models with ALK mutations that confer resistance to other small molecule ALK inhibitors.

Also known as: X-396

[14C]Ensartinib

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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. Highly effective methods of birth control include using condom, contraceptive sponge, contraceptive gel, contraceptive film, intrauterine device, oral or injectable contraceptive pill, hypodermic implants or others;
• Must understand, and voluntarily sign the informed consent, comply with the requirements of the study

You may not qualify if:

• 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;
• History of clinically significant disease or infection within 1 month before entering the study;
• 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, and is judged as clinically significant by the investigator；
• Abnormal ALP, 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 or herbal drug, except for vitamins and paracetamol;
• 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;
• 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, hydroxypropyl methylcellulose);
• Have donated 500ml or more of blood or plasma 2 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;

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (1)

Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine

Nanjing, Jiangsu Provence, 210005, China

RECRUITING

Related Publications (3)

• Nijenhuis CM, Schellens JH, Beijnen JH. Regulatory aspects of human radiolabeled mass balance studies in oncology: concise review. Drug Metab Rev. 2016 May;48(2):266-80. doi: 10.1080/03602532.2016.1181081. Epub 2016 May 17.

  PMID: 27186889 BACKGROUND

• Penner N, Klunk LJ, Prakash C. Human radiolabeled mass balance studies: objectives, utilities and limitations. Biopharm Drug Dispos. 2009 May;30(4):185-203. doi: 10.1002/bdd.661.

  PMID: 19544285 BACKGROUND

• Zhou S, Liu W, Zhou C, Zhang L, Xie L, Xu Z, Wang L, Zhao Y, Guo L, Chen J, Ding L, Mao L, Tao Y, Zhang C, Ding S, Shao F. Mass balance, metabolic disposition, and pharmacokinetics of [14C]ensartinib, a novel potent anaplastic lymphoma kinase (ALK) inhibitor, in healthy subjects following oral administration. Cancer Chemother Pharmacol. 2020 Dec;86(6):719-730. doi: 10.1007/s00280-020-04159-0. Epub 2020 Oct 12.

  PMID: 33044566 DERIVED

Related Links

• \[6\] CFR 361.1 Radioactive Drugs for Certain Research Uses.

MeSH Terms

Interventions

ensartinib

Study Officials

• Feng Shao

  Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Shao

CONTACT

+8613851691161; shaofengnj@163.com

Sufeng Zhou

CONTACT

+8615952052032; zhousfhappy@163.com

Study Design

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

Study Record Dates

• First Submitted: December 26, 2018
• First Posted: January 15, 2019
• Study Start: December 28, 2018
• Primary Completion: June 1, 2019
• Study Completion: October 1, 2019
• Last Updated: January 15, 2019

Record last verified: 2019-01

Locations

CN (1)