CTRI/2020/03/024404 [Registered on: 31/03/2020] Trial Registered Prospectively
Last Modified On:
14/10/2021
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Imatinib Mesylate Oral Solution 400mg/5ml with Gleevec® (Imatinib mesylate) Tablets 400mg in adult human subjects with Chronic Myeloid Leukemia or Gastrointestinal Stromal Tumors under fed condition.
An open label, multicenter, balanced, randomized, two-treatment, two-period, two-sequence, two-way crossover, multiple-dose, steady state, comparative oral bioavailability study of Imatinib Mesylate Oral Solution 400mg/5ml of Shilpa Medicare Limited, India with Gleevec® (Imatinib mesylate) Tablets 400mg of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, in adult human patients with Chronic Myeloid Leukemia or Gastrointestinal Stromal Tumors under fed condition.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sandeep Singh
Designation
Director Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Scientific Query
Name
Dr Sandeep Singh
Designation
Director Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Public Query
Name
Dr Sandeep Singh
Designation
Director Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
Willing and able to provide voluntary informed consent and
to follow the protocol requirements
Male or Female aged 18 to 65 years both inclusive having
body mass index BMI at least 17.00 calculated as weight in
kg/height in m2
Patients with Philadelphia chromosome positive Chronic
Myeloid Leukemia ph+ CML in their first three months of
treatment in chronic phase and who are on a stable dose of
400mg of Imatinib and requiring a daily dose of Imatinib
monotherapy OR Patients with Kit CD117 positive
unresectable and/or metastatic malignant Gastrointestinal
Stromal Tumor GIST who are on a stable dose of 400mg of
Imatinib and requiring a daily dose of Imatinib monotherapy
Eastern Cooperative Oncology Group ECOG performance
status less or equal to 2
Acceptable hematology status
Hemoglobin greater or equal to 9 g per dL
Absolute neutrophil count ANC greater or equal to 1500 cells per mm3
Platelet count greater or equal to 100,000 cells per mm3
Acceptable liver function:
Alanine aminotransferase less or equal to 2.5 X ULN
Aspartate aminotransferase AST less or equal t 2.5 X ULN
Bilirubin less or equal to 1.5 X ULN
alkaline phosphatase less or equal to 2.5 X ULN
Patients with creatinine clearance greater or equal to 60 mL per minute
Patients with life expectancy of at least 3 months at the time
of enrolment
Female Patients with negative serum pregnancy test at
Screening
Women of child bearing potential, defined as women
physiologically capable of becoming pregnant, unless they are
using effective method of contraception during dosing of the
investigational product practicing two acceptable methods of
contraception
Acceptable methods of contraception are
Oral or parenteral injection, patch or implant hormonal contraception which has been used continuously for at least one month prior to the first dose of study medication
Intrauterine device IUD or intrauterine system IUD per IUS
Double barrier method of contraception Condom and occlusive cap or condom and spermicidal agent
Male sterilization at least 6 months prior to the screening, should be the sole male partner for that Patient
Female sterilization (surgical bilateral oophorectomy) or tubal ligation within at least 6 weeks prior to study participation
Total abstinence, partial abstinence is not acceptable
No history of addiction to any recreational drug or drug dependence or alcohol addiction
ExclusionCriteria
Details
1. Known hypersensitivity or contraindication to Imatinib or to
any of the components of investigational product
2. Patients with Ph+Chronic Myeloid Leukemia in accelerated
phase or blastic phase
3. Patients with previous/current history of hematopoietic stem cell transplantation
4. Patients who have undergone Thyroidectomy
5. Patients on concomitant medication with drugs known to be inhibitors and/or inducers of CYP3A4 (Refer Appendix B)
6. Patients taking medications that irreversibly inhibit platelet function or anticoagulants
7. Patients with GI hemorrhage
8. Known CNS metastasis
9. Major surgical procedure (including periodontal) within 28 days of first dose of investigational product
10. Surgical or other non-healing wounds
11. Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV)
12. Patients with positive urine screen for Drugs of Abuse
13. Patients with positive alcohol breath test
14. History of other malignancies in the last 5 years (except in situ cancer or basal or squamous cell skin cancer)
15. Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents. Exceptions are alopecia (any grade is acceptable), Haemoglobin greater or equal to 9.0 g/dL, fatigue (Grade 2 is acceptable), and peripheral neuropathy (stable
Grade 2 is acceptable) (Per National Cancer Institute [NCI]Common Terminology Criteria for Adverse Events [CTCAE], V5.0)
16. Participation in any clinical study within 90 days prior to receiving the first dose of Investigational Product
17. Loss of greater or equal to 350 ml of blood within 90 days prior to receiving the first dose of investigational product for the current study
18. Any other medical condition or uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.) that, in the opinion of the Investigator, may make it undesirable for the patient to participate in the study
19. Any other condition(s) which could significantly interfere with protocol compliance including, but not limited to, dementia, psychosis, cognitive impairment, altered mental status, or other major psychiatric disorder
20. Lactating women.
To compare and evaluate the multiple dose oral bioavailability of Imatinib Mesylate Oral Solution 400mg/5ml of Shilpa Medicare Limited with Gleevec® (Imatinib mesylate) Tablets 400mg of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, in adult human patients with Chronic Myeloid Leukemia or Gastrointestinal Stromal Tumors under fed condition.
Day:1-Pre-dose blood sample within 1.00 hour prior to dosing, Day:6 and 14- Pre-dose blood sample (-48.0) and Day:7 and 15- Pre-dose blood sample (-24.0) within 1.00 hour prior to dosing, Day:8and16- Pre-dose blood sample (0.0) within 1 hour prior to dosing for 0.5 hours, 1.0 hrs., 1.5 hrs., 2.0 hrs., 2.5 hrs., 3.0 hrs., 3.5 hrs., 4.0 hrs., 5.0 hrs., 6.0 hrs., 8.0 hrs., 10.0 hrs., 12.0 hrs., 16.0 hrs. within ± 02 minutes, Day:09and17 – 24 hrs. within ± 02 minutes
The Study isan open label, multicenter, balanced, randomized, two-treatment, two-period, two-sequence, two-way crossover, multiple-dose, steady state, comparative bioavailability study of Imatinib Mesylate Oral Solution 400mg/5ml of Shilpa Medicare Limited, India with Gleevec® (Imatinib mesylate) Tablets 400mg of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, in adult human patients with Chronic Myeloid Leukemia or Gastrointestinal Stromal Tumors under fed condition.
Primary Objective: To compare and evaluatemultiple dose oral bioavailability of Imatinib Mesylate Oral Solution 400mg/5ml of Shilpa medicare Limited, India with Gleevec®(Imatinib mesylate) Tablets 400mg of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, in adult human patients with Chronic Myeloid Leukemia or Gastrointestinal Stromal Tumors under fed condition.
Secondary Objective: To monitor the adverse events and to ensure the safety of patients.