Bioequivalence Study of Mesylate Imatinib Capsule in Chronic Myeloid Leukemia Body

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01795716
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 2.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: mesylate imatinib capsule; Drug: Glivec	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bioequivalence Study of Mesylate Imatinib Capsule in Chronic Myeloid Leukemia Body
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mesylate imatinib capsule Single and multiple oral mesylate imatinib capsule 400mg qd	Drug: mesylate imatinib capsule; Single and multiple oral mesylate imatinib capsule 400mg qd; Other Names: 111201
Active Comparator: Glivec Single and multiple oral Glivec 400mg qd	Drug: Glivec; Single and multiple oral Glivec 400mg qd; Other Names: Mesylate Imatinib tablet

Outcome Measures

Primary Outcome Measures

1. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shanghai Jiaotong University School of Medicine Ruijin Hospital	Shanghai		China	200025

Sponsors and Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Investigators

• Principal Investigator: Shen Zh xiang, doctor, Shanghai Jiaotong University School of Medicine Ruijin Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01795716
• Other Study ID Numbers: YMTN-1.0
• First Posted: Feb 21, 2013
• Last Update Posted: May 19, 2015
• Last Verified: May 1, 2015

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Mesylate Imatinib Capsule First, Then Glivec	Glivec First, Then Mesylate Imatinib Capsule
Arm/Group Description	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 .	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 .
Period Title: First Intervention (13 Days)
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0
Period Title: First Intervention (13 Days)
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0
Period Title: First Intervention (13 Days)
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Mesylate Imatinib Capsule First, Then Glivec	Glivec First, Then Mesylate Imatinib Capsule	Total
Arm/Group Description	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 .	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 .	Total of all reporting groups
Overall Participants	10	11	21
Age (Count of Participants)
<=18 years	1 10%	1 9.1%	2 9.5%
Between 18 and 65 years	9 90%	10 90.9%	19 90.5%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Geometric Mean (Full Range) ]
Geometric Mean (Full Range) [years]	33	33	33
Sex: Female, Male (Count of Participants)
Female	3 30%	5 45.5%	8 38.1%
Male	7 70%	6 54.5%	13 61.9%
Region of Enrollment (participants) [Number]
China	10 100%	11 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mesylate Imatinib Capsule	Glivec
Arm/Group Description	Eligible subjects were assigned to receive a single and multiple 400 mg oral dose Mesylate Imatinib Capsule	Eligible subjects were assigned to receive a single and multiple 400 mg oral dose Glivec
Measure Participants	21	21
Mean (Standard Deviation) [mcg*hr/mL]	37256 (11442)	37206 (10620)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mesylate Imatinib Capsule, Glivec
	Comments	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.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The 90%CIs 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.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	29 days
Arm/Group Title	Mesylate Imatinib Capsule		Glivec
Arm/Group Description	Subjects were assigned to receive a single and multiple 400 mg oral dose Mesylate Imatinib Capsule		Subjects were assigned to receive a single and multiple 400 mg oral dose Glivec
All Cause Mortality
	Mesylate Imatinib Capsule		Glivec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Mesylate Imatinib Capsule		Glivec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Mesylate Imatinib Capsule		Glivec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/21 (47.6%)		13/21 (61.9%)
Gastrointestinal disorders
nausea and vomit	10/21 (47.6%)	10	13/21 (61.9%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.