A Bioequivalence Study of Dasatinib Tablet

A Bioequivalence Study Between the Generic Dasatinib Tablet and Reference Product in Vivo

This is a clinical study to evaluate the bioequivalence of dasatinib tablet produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and Sprycel® produced by Bristol Myers Squibb after single dose in healthy subjects, so as to provide reference for clinical evaluation and clinical medication; to observe the safety of the dasatinib tablet and the reference drug Sprycel® in healthy subjects under fasting and fed states.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myelogenous, Chronic
• Intervention / Treatment: Drug: CTTQ Dasatinib tablet; Drug: Sprycel Dasatinib tablet

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • Affiliated Hospital of Changchun University of Traditional Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects signed the informed consent form before the trial and fully understood the trial content, process and possible adverse reactions;
• Subjects were able to complete the study according to the requirements of the trial protocol;
• Subjects have no disease history of heart, liver, kidney, digestive tract, nervous system, mental disorders and metabolic disorders;
• Healthy male and female subjects at age of 18-55;
• Male subjects weighted ≥ 50 kg, female subjects weighted ≥ 45kg, and the body mass index (BMI) was18 kg/m2 to 28 kg/m2 (including the cutoff value).
• Normal or not clinical significant abnormal vital signs, physical examination, laboratory examination, ECG and imaging examination have;
• The female blood pregnancy test was negative, and the subjects (including male subjects) had no pregnancy plan from 2 weeks before administration to at least 1 month after the last dose of the study drug and voluntarily took effective contraceptive measures.

Exclusion Criteria:

• Subjects with the following diseases or with clinically significant abnormalities in clinical laboratory examinations or other clinical findings of clinical significance (including but not limited to gastrointestinal, kidney, liver, neurological, blood, endocrine, tumor, lung, immune, psychiatric, cardiovascular and cerebrovascular diseases);
• Subjects with known allergies to dasatinib or its excipients;
• Subjects smoked at least 5 cigarettes per day 3 months before screening;
• Subjects with a history of drug or alcohol abuse;
• Subjects who donated blood within 3 months before screening;
• Subjects who took any drugs that could change liver enzyme activity 28 days before taking the study drug;
• Subjects who have taken any drugs, vitamin products or herbal medicines within 14 days before clinical trial;
• Subjects who smoked and drank alcohol during the trial, or performed strenuous exercise before the trial;
• Subjects have taken the study drug and participated in other drug clinical trials within 2 months before the clinical trial;
• Subjects with abnormal vital sign results;
• Subjects with abnormal clinical medical investigation;
• Subjects who had clinically significant ECG abnormalities;
• Subjects with abnormal chest X-rays;
• Subjects with the positive results of Hepatitis (including hepatitis B and C), AIDS, and syphilis;
• Female subjects who were lactating or serum-positive for pregnancy;
• Those who screen positive for drugs or have a history of drug abuse in the past five years or have used drugs in the three months prior to the trial;
• Subjects with acute illnesses that occurred during the screening period or prior to study drug administration;
• Acute disease occurs during pre-study screening stage or before study medication
• Subjects with a history of peptic ulcer or intracranial hemorrhage;
• Subjects had any disease that increased the risk of bleeding,
• Subjects were unable to comply with ward management regulations;
• Subjects cannot complete the trial for personal reasons;
• Subjects judged unsuitable for participating in this trial by other investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTTTQ Dasatinib tablet; Subjects receive CTTQ dasatinib tablet under fasting/fed	Drug: CTTQ Dasatinib tablet; Dasatinib tablet is an oral tyrosinekinase inhibitor produced by Chia Tai Tianqing Pharmaceutical Group.
Experimental: Sprycel Sprycel; Subjects receive Sprycel under fasting/fed	Drug: Sprycel Dasatinib tablet; Sprycel Dasatinib tablet is an oral tyrosinekinase inhibitor produced by Bristol Myers Squibb.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum (peak) plasma drug concentration (Cmax)	Maximum (peak) plasma drug concentration is a Pharmacokinetic parameter	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
Area under the plasma concentration-time curve from time zero to time t (AUC0-t)	Area under the plasma concentration-time curve from time zero to time t is a Pharmacokinetic parameter	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
The area under the plasma concentration curve from 0 to infinity (AUC0-∞)	The area under the plasma concentration curve from 0 to infinity	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum concentration (Tmax)	Time to reach maximum (peak) plasma concentration following drug administration	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
Elimination half-life (t1/2)	The time required for the highest concentration of the drug in plasma to decrease by half	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
Apparent end elimination rate constant (λz)	Terminal disposition rate constant/terminal rate constant	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
Apparent volume of distribution (Vd/F)	Apparent volume of distribution after oral administration	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
Apparent total body clearance (CL/F)	Apparent total clearance of the drug from plasma after oral administration	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
Relative bioavailability	Bioavailability (systemic availability of the administered dose)	1 hour before administration and 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after administration.
Adverse Event	Adverse events of subjects occured during the trial	Up to day 11
Serious Adverse Event	Serious Adverse events of subjects occured during the trial	Up to day 11
Body temperature	Monitor the body temperature of subjects and report abnormal body temperature	Up to day 11
Pulse	Monitor the pulse of subjects and report abnormal pulse	Up to day 11
Blood pressure	Monitor the blood pressure of subjects and report abnormal blood pressure	Up to day 11
CTCAE v5.0	The Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (physical examination)	Up to day 11
The Number of participants with abnormal laboratory examinations	laboratory examination, such as liver function, kidney function, coagulation function, blood routine, urine routine	Up to day 11

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2018
• Primary Completion (Actual): October 3, 2018
• Study Completion (Actual): October 8, 2019

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 7, 2022

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: ZDTQ-BE-2017-DSTN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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