To Evaluate the Effect of Food on the Pharmacokinetic Characteristics of Alkotinib Capsules in Healthy Subjects

To Evaluate the Effect of Food on the Pharmacokinetic Characteristics of Alkotinib Capsules in Healthy Subjects,A Single Center, Open, Randomized, Single Dose, Two Period, Two Sequence, Crossover Phase I Clinical Trial

To evaluate the safety and tolerability of food to Alkotinib Capsules in healthy subjects

Study Overview

• Status: Completed
• Conditions: NSCLC
• Intervention / Treatment: Drug: Alkotinib（300mg)

Detailed Description

Alkotinib is an insulin receptor tyrosine kinase inhibitor that selectively inhibits anaplastic lymphoma Kinase and proto-oncogene protein ROS1。Alkotinib is expected to be used in the treatment of ALK positive and ROS1 positive metastatic non-small cell lung Cancer and other cancers include patients with non-small cell lung cancer who are resistant to treatment with the first generation ALK inhibitor, such as kezotinib。

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Bethune Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• sign the informed consent before the clinicaltrial, and fully understand the clinicaltrial content, process and possible adverse event.
• Be able to complete the research according to the clinicaltrial protocol.
• Subjects (including sexual partners) were willing to be screened up to 6 months after the last study drug administration No family planning and voluntary effective contraceptive measures, the specific contraceptive measures see appendix.
• Male and female subjects aged 18 to 55 years (including 18 and 55 years).
• The weight of male subjects should not be less than 50 kg and that of female subjects should not be less than 45 kg. The body of the Body mass index (BMI) = weight (kg)/height 2 (m2), with a BMI of 18~28 kg/m2 range (including critical value).

• Normal or abnormal physical examination and vital signs have n

  • clinical significance.

Exclusion Criteria:

• Smoking more than 5 cigarettes per day during the first 3 months of the study
• Allergic constitution (multiple drug and food allergies).
• A history of drug and/or alcohol abuse (14 units of alcohol per week: 1 unit = beer 285)ML, or liquor 25 mL, or wine 100 mL)
• Blood donation or massive blood loss within 3 months prior to clinical trial screening (> 450ml)
• Any drugs that alter liver enzyme activity were taken 28 days before screening.
• Within 14 days prior to screening，took any prescription, over-the-counter, vitamin products or Herbs.
• Special diet (including dragon fruit, mango, grapefruit, etc.) or drama in 2 weeks，before screening strenuous exercise or other factors affecting drug absorption, distribution, metabolism, excretion, etc.;
• CYP3A inhibitors (e.g., atanavir, talymycin, clarithromycin, etc.), CYP3A inducers (e.g Drugs metabolized by CYP2C8 (such as amodiaquine, silvastatin, etc.) and CYP2C9 metabolism Drugs such as diclofenac, ibuprofen, etc.
• There have been major changes in diet or exercise habits recently.
• Have taken a study drug or participated in a clinical trial of the drug within three months prior to taking the study drug Check.
• A history of dysphagia or any gastrointestinal illness that affects drug absorption, cholecystitis or cholecystectomy In addition to the history;
• Any disease that increases the risk of bleeding, such as hemorrhoids, acute gastritis or stomach and duodenum Ulcer etc.
• Subjects who could not tolerate standard meals
• Abnormal ecg has clinical significance, or QTc interval >450 ms, or heart rate or pulse < 55 times /Points.
• Any pulmonary disease, including but not limited to interstitial pneumonia, allergic pneumonia, occlusion.Bronchiolitis, pulmonary interstitial fibrosis,interstitial lung disease (ILD), or any pre-existing disease History.
• Female subjects were lactating during the screening period or during the test or had positive serum pregnancy results sex.
• Clinical laboratory examination has clinical significance abnormality, or other clinical findings within 12 months before screening the following diseases (including but not limited to gastrointestinal tract, heart, lung, kidney,Liver, pancreas, nerve, blood, endocrine, tumor, immune, mental or cardiovascular diseases）.
• Screening for viral hepatitis (including hepatitis b and c), AIDS antibody and syphilis spirochete antibody positive.
• Ingested chocolate, any caffeine containing it or the yellow purinate-rich drug 48 hours before taking it.
• Any use of alcohol within 48 hours prior to taking the study drug.
• Positive urine screening or drug use in the past 5 years.
• Subjects considered to have other factors unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Alkotinib（300mg）First empty stomach, after the meal; Alkotinib（300mg），Subjects need to be fasting overnight for at least 10 hours before being warmed to 240 mL on an empty stomach Water service, lunch 4 hours later, dinner 10 hours later.	Drug: Alkotinib（300mg); 1. First empty stomach, after the meal.2. After eating first, after fasting.
EXPERIMENTAL: Alkotinib（300mg）After eating first, after fasting; Alkotinib（300mg），Subjects need to be fasting for at least 10 hours overnight, starting 30 min before taking the medication A standard meal (800-1000 CAL) can be taken before taking the medicine, and 240 mL warm water can be taken after the meal Lunch hours later, dinner 10 hours later.	Drug: Alkotinib（300mg); 1. First empty stomach, after the meal.2. After eating first, after fasting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum blood concentration	up to 120 hours
AUC0-t	Area under the plasma concentration - time curve from 0 to the last measurable concentration time point t	up to 120 hours
AUC0-∞	Area under the concentration - time curve from zero to infinity	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	To the maximum blood concentration time	up to 6 months
t1/2	Plasma drug half-life	up to 6 months
λz	14/5000 The rate constant of plasma concentration elimination in terminal phase	up to 6 months
CL/F	Apparent clearance	up to 6 months
VZ/F	Apparent volume	up to 6 months

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Investigators: Study Chair: yanhua Ding, MD, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2019
• Primary Completion (ACTUAL): December 16, 2019
• Study Completion (ACTUAL): December 16, 2019

Study Registration Dates

• First Submitted: July 23, 2019
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (ACTUAL): July 25, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 7, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Alkotinib
• Other Study ID Numbers: ZGALK003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share date of the trial

Drug and device information, study documents

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