Chronic Myeloid Leukemia
Conditions
Brief summary
1. purpose: To conduct the relative bioavailability study of a single dose and multiple doses of imatinib mesylate capsule (Jiangsu Chia-Tai Tianqing Pharmacy Co. Ltd.) versus Glivec (Novartis Pharma Stein AG). 2. Experimental Design： Two-period crossover design 3. Test drug: imatinib mesylate capsule Reference drug: Glivec 4. Sample size：20
Detailed description
To conduct the relative bioavailability study of a single dose and multiple doses of imatinib mesylate capsule(Jiangsu Chia-Tai Tianqing Pharmacy Co. Ltd.) versus Glivec (Novartis Pharma Stein AG) and compare the bioequivalence and pharmacokinetics of the two products in 20 patients with chronic myeloid leukemia.
Interventions
DRUGmesylate imatinib capsule
Single and multiple oral mesylate imatinib capsule 400mg qd
DRUGGlivec
Single and multiple oral Glivec 400mg qd
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with chronic myeloid leukemia; * Age: 18-65 years,gender:both. * Weight: standard weight ± 20% within, and avoid weight disparity is too large; * No previous radiation therapy, chemotherapy, or surgery within 1 weeks before treatment with imatinib; * Performance status 0 to 3 (WHO scale); Life expectancy greater than 3 months; * No other malignancy; * Adequate hepatic, renal, and bone marrow function (WBC≥3.0×109/L，ANC≥1.5×109/L，PLT≥80×109/L. Serum bilirubin≤1.5×the institutional upper limit of normal, ALT、ALP≤2.5×the institutional upper limit of normal, creatinine≤1.5×the institutional upper limit of normal); * Ability to understand objectives of the study, the study procedure, the pharmacological properties of the drug and possible adverse reactions and the willingness to sign a written informed consent.
Exclusion criteria
* Suffering from heart, liver, kidney disease or severe acute and chronic gastrointestinal diseases; * Pregnant or lactating women and be sensitive to drug; * Subjects are thought unsuitable for the study by investigators; * Inability to comply with protocol or study procedures in the opinion of the investigator; * Attending other clinical trials or attended other clinical trials 3 months ago.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under Curve (AUC) Time Frame: Predose, 0.5,1,1.5,2,3,5,8,12,24,48,72hours Post-dose | predose, 0.5,1,1.5,2,3,5,8,12,24,48,72hours post-dose |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mesylate Imatinib Capsule First, Then Glivec Eligible subjects were randomly assigned to receive a single and multiple 400 mg oral dose Mesylate Imatinib Capsule during the first study period. In the first phase of the multiple-dose administration, the groups were given Mesylate Imatinib Capsule 400 mg once daily in the morning for ten consecutive days. After ten-day washout period, then Glivec was administered under the same protocol . | 10 |
| Glivec First, Then Mesylate Imatinib Capsule Eligible subjects were randomly assigned to receive a single and multiple 400 mg oral dose Glivec during the first study period. In the first phase of the multiple-dose administration, the groups were given Glivec 400 mg once daily in the morning for ten consecutive days. After ten-day washout period, then Mesylate Imatinib Capsule was administered under the same protocol . | 11 |
| Total | 21 |
Baseline characteristics
| Characteristic | Glivec First, Then Mesylate Imatinib Capsule | Mesylate Imatinib Capsule First, Then Glivec | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Age, Continuous | 33 years | 33 years | 33 years |
| Region of Enrollment China | 11 participants | 10 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 21 | 13 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Area Under Curve (AUC) Time Frame: Predose, 0.5,1,1.5,2,3,5,8,12,24,48,72hours Post-dose
Time frame: predose, 0.5,1,1.5,2,3,5,8,12,24,48,72hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesylate Imatinib Capsule | Area Under Curve (AUC) Time Frame: Predose, 0.5,1,1.5,2,3,5,8,12,24,48,72hours Post-dose | 37256 mcg*hr/mL | Standard Deviation 11442 |
| Glivec | Area Under Curve (AUC) Time Frame: Predose, 0.5,1,1.5,2,3,5,8,12,24,48,72hours Post-dose | 37206 mcg*hr/mL | Standard Deviation 10620 |
Comparison: The 90% confidence intervals of the test/reference ratios for AUC0-∞ and Cmax were determined. Log-transformed data were used in the analysis. Following international guidelines (including those of the SFDA), the test and reference for mutations were considered bioequivalent if the 90% CIs of the test/reference ratios of AUC was within range of 0.80 to 1.25 and Cmax was within 0.70 to 1.43.p-value: <0.05ANOVA