ALK-POSITIVE NSCLCPhase 1NCT03804541
The Absorption, Metabolism and Excretion of [14C]Ensartinib in Human
A Phase 1 study testing Ensartinib in people with ALK-POSITIVE NSCLC, run by Betta Pharmaceuticals Co., Ltd. at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- ALK-POSITIVE NSCLC
- What is being tested?
- Ensartinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 28 Dec 2018to Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- A subject will not be eligible for study participation if he meets any of the exclusion criteria:
- 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)
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- 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;
- History of drug or alcohol abuse;
- 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(MOP, METmAMP, MTD, THC, AMP positive) within last 3 months;
- Subject with mentally ill and could not understand the property, scope and possible consequences of the study;
- subject in prison or whose freedom is restricted by administrative or legal issues;
- Failure to comply with clinical study protocols, such as non-cooperation, follow-up visit and completion of entire study;
- Investigator, pharmacist, CRC or research associate;
- Investigators think that subjects are not suitable to participate in the study;
- Subjects who have participated in radiolabeled clinical study prior to drug administration;
- 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).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
Nanjing, Jiangsu Provence, 210005
Feng Shao，Associate Professor, PhD, +8613851691161, shaofengnj@163.com
About this study
Official title: A Single-center, Open-label, Single-dose Phase I Study to Investigate the Absorption, Metabolism and Excretion of [14C]Ensartinib (X-396) After a Single Oral 200mg (100µCi) Dose in Healthy Chinese Male Subjects
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.
Read the detailed description
Subjects who had signed informed consent and meet inclusion criteria and no exclusion criteria are admitted to Phase I Clinical Unit two days prior to dosing (D-2). On the morning of Day 1 before dosing, subjects will be transferred to nuclear medical ward. And after an overnight fast of at least 10 h, subjects will receive a single oral dose of 200 mg (100 μCi) of [14C]Ensartinib as an oral suspension. Then, after two days of the dosing, subjects will be transferred back to Phase I Clinical Unit ward and confined to this unit until blood or excreta sampling and safety monitoring at the designated time points or intervals are complete
- Conditions
- ALK-POSITIVE NSCLC
- Being tested
- Ensartinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnsartinibDrug
Also called X-396
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.
| Study group | Role | What they receive |
|---|---|---|
| [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。 Receives: Drug: Ensartinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radioactivity concentration of each plasma sample
Use liquid scintillation counter to evaluate Radioactivity concentration of each plasma（DPM/ml) sample
Measured: Day1-Day15
Radioactivity concentration of each urine samples
Use liquid scintillation counter to evaluate Radioactivity concentration of each urine（DPM/ml） sample
Measured: Day1-Day15
Radioactivity concentration of each feces sample
Use liquid scintillation counter to evaluate Radioactivity concentration of each feces（DPM/g） sample
Measured: 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.
Measured: Day1-Day15
Secondary outcomes (2)
Plasma drug concentrations
To determine the plasma concentrations of Ensartinib with validated LC-MS/MS method for obtaining its pharmacokinetics parameters;
Measured: Day1-Day15
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
According to CTCAE v4.03, the number and frequency of adverse events after a single dose of test drug were assessed.
Measured: Day1-Day15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2019
- Study start28 Dec 2018
- Primary completionJun 2019 (estimated)
- Study completionOct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ALK-POSITIVE NSCLCStudies of the same condition, open and under way.
- More trials run by Betta Pharmaceuticals Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Betta Pharmaceuticals Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Feng Shao, Principal investigator, Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03804541
- Sponsor's protocol ID
- BTP-44316
- Status last verified
- Jan 2019
- First submitted
- 26 Dec 2018
- Last updated
- 15 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 27186889Penner 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.
PubMed 19544285Zhou 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.
PubMed 33044566
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label, Single-dose Phase I Study to Investigate the Absorption, Metabolism and Excretion of [14C]Ensartinib (X-396) After a Single Oral 200mg (100µCi) Dose in Healthy Chinese Male Subjects
- ClinicalTrials.gov ID
- NCT03804541
- Acronym / sponsor ID
- BTP-44316
- Conditions
- ALK-POSITIVE NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Betta Pharmaceuticals Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 28 Dec 2018 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Oct 2019 (estimated)
- First posted
- 15 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Subjects who had signed informed consent and meet inclusion criteria and no exclusion criteria are admitted to Phase I Clinical Unit two days prior to dosing (D-2). On the morning of Day 1 before dosing, subjects will be transferred to nuclear medical ward. And after an overnight fast of at least 10 h, subjects will receive a single oral dose of 200 mg (100 μCi) of [14C]Ensartinib as an oral suspension. Then, after two days of the dosing, subjects will be transferred back to Phase I Clinical Unit ward and confined to this unit until blood or excreta sampling and safety monitoring at the designated time points or intervals are complete
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [14C]Ensartinib | Experimental | Drug: EnsartinibTo 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。 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (25 listed)
- A subject will not be eligible for study participation if he meets any of the exclusion criteria:
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnsartinibAlso: X-396A 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. | Drug | [14C]Ensartinib |
Primary outcome
Radioactivity concentration of each plasma sample
Time frame: Day1-Day15
Use liquid scintillation counter to evaluate Radioactivity concentration of each plasma（DPM/ml) sample
Radioactivity concentration of each urine samples
Time frame: Day1-Day15
Use liquid scintillation counter to evaluate Radioactivity concentration of each urine（DPM/ml） sample
Radioactivity concentration of each feces sample
Time frame: Day1-Day15
Use liquid scintillation counter to evaluate Radioactivity concentration of each feces（DPM/g） sample
Total recovery of radioactivity in urine and feces
Time frame: Day1-Day15
Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample.
2 secondary outcomes
Plasma drug concentrations
Time frame: Day1-Day15
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time frame: Day1-Day15
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2019.
- Background: PubMed 27186889Nijenhuis 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.
- Background: PubMed 19544285Penner 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.
- Derived from this study: PubMed 33044566Zhou 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.
- \[6\] CFR 361.1 Radioactive Drugs for Certain Research Uses.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Feng Shao principal investigator
Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ensartinib in people with ALK-POSITIVE NSCLC, run by Betta Pharmaceuticals Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Feng Shao (+8613851691161, shaofengnj@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radioactivity concentration of each plasma sample (time frame: Day1-Day15). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03804541, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2019.