CTRI/2020/10/028441 [Registered on: 16/10/2020] Trial Registered Prospectively
Last Modified On:
22/02/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
Pharmacokinetic Study of Pazopanib in subjects with Advanced renal cell carcinoma.
Scientific Title of Study
A randomized, open label, multi-center, two-treatment, two-period, two-sequence, two-way cross-over, multiple dose, steady-state Bioequivalence (BE) study of Pazopanib HCl 200mg Tablets at a dose of 800 mg (4 x 200 mg tablets) of Torrent Pharmaceuticals Ltd., India with VOTRIENT® (Pazopanib HCl 200mg) Tablets at a dose of 800 mg (4 x 200 mg tablets) of Novartis Pharmaceuticals Corporation, USA in subjects with Advanced renal cell carcinoma under fasting condition.
Ethics Committee Bangalore Cancer Centre (IEC-BCC)
Approved
Ethics Committee GSVM Medical College
Approved
Ethics Committee Isha Hospital
Approved
Ethics Committee S.M.S. Medical College and Attached Hospitals
Approved
HCG-Central Ethics Committee
Approved
IEC IMS and SUM Hospital
Approved
IEC-MMC and RI and Associated Hospital Mysore Medical College and Research Institute
Approved
Instituitional Ethics Committee Sparsh Hospital
Approved
Institution Ethics Committee Post Graduate Institute of Medical Education and Research
Approved
Institutional EC, Apex Hospital
Approved
Institutional Ethics Committee Erode Cancer
Approved
Institutional Ethics Committee Sparsh Hospital
Approved
Institutional Ethics Committee, KLE University
Approved
Kiran Hospital Ethics Committee
Approved
Lokmanya Medical Resaerch Centre Lokmanya Hospital
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Medstar Speciality Hospital Ethics Committee
Approved
MNJIORCC Ethics Committee
Approved
NIRMAL HOSPITAL ETHICS COMMITTEE
Approved
NOBLE HOSPITAL INSTITUTIONAL ETHICS COMMITTEE
Approved
Shree Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C649||Malignant neoplasm of unspecifiedkidney, except renal pelvis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Pazopanib HCl 200 mg Tablets of Torrent Pharmaceuticals Ltd., India
Dose:800mg (4 Tablet of 200 mg),
Frequency: Once Daily,
Route of Administration: Oral
Duration of therapy: 36 Days
Comparator Agent
VOTRIENT® (Pazopanib HCl) 200 mg Tablets of Novartis Pharmaceuticals Corporation, USA
Dose:800mg (4 Tablet of 200 mg),
Frequency: Once Daily,
Route of Administration: Oral
Duration of therapy: 36 Days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements.
2. Subjects aged greater than 18 years having Body Mass Index at least 17.00 calculated as weight in kg per height in m2.
3. Subjects with confirmed diagnosis of advanced renal cell carcinoma, already receiving stable dose of Pazopanib HCl tablets of 800 mg per day since at least last 4 weeks.
4. Subjects able to swallow and retain oral medication
5. Life expectancy of at least 3 months at the time of enrolment.
6. Acceptable hematology status:
a. Hemoglobingreater than or equal to9.0 g per dL
b. Absolute neutrophil count greater than or equal to1500 cells per mm3
c. Platelet count greater than or equal to 1,00,000 cells per mm3
7. Acceptable liver function:
a. Alanine aminotransferase (ALT) less than or equal to 2 X ULN
b. Aspartate aminotransferase (AST) less than or equal to 2X ULN
c. Bilirubin less than or equal to ULN
d. Alkaline phosphatase less than or equal to 5 X ULN
8. Subjects with Creatinine clearance greater than or equal to 60 mL per minute
9. Cardiac ejection fraction greater than or equal to 50 Percentage by echocardiogram within 28 days of first dose of Investigational Product.
10. Male subjects (including those who had a vasectomy) with female partners of
reproductive potential must agree to use condoms from screening, during study and for at least two weeks after treatment discontinuation.
11. Female subjects with negative serum pregnancy test at screening and at Day 0.
12. Women of childbearing potential, (defined as women physiologically capable of becoming pregnant, unless they are using effective method of contraception during dosing of the investigational product) practicing acceptable methods of contraception during study and for at least two weeks after treatment discontinuation.
Acceptable methods of contraception are:
a. Oral or other (e.g. injection, patch or implant) hormonal contraception which has been used continuously for at least one month prior to the first dose of study medication
b. Intrauterine device IUD or intrauterine system IUD or IUS
c. Double barrier method of contraception Condom and occlusive cap or condom and spermicidal agent
d. Male sterilization at least 6 months prior to the screening, should be the sole male partner for that subject
e. Female sterilization surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to study participation
f. Total abstinence, partial abstinence is not acceptable.
13. No history of addiction to any recreational drug or drug dependence or alcohol addiction.
ExclusionCriteria
Details
1. Known hypersensitivity to Pazopanib or the components of investigational product.
2. History or presence of any uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.).
3. Subjects with hypokalemia, hypomagnesaemia, long QT syndrome (QTc of >450 msec in male or QTc of > 470 msec in female) or history of cardiac disease at the time of screening
4. Subjects found with major vascular disease or VTE in previous 6 months from the screening
5. Currently receiving or anticipated to receive any medications or substances that are strong inhibitors or inducers of the CYP3A4 and CYP450 inducer or inhibitor; narrow therapeutic index drugs that are metabolized by CYP3A4, CYP2D6 or CYP2C8; simvastatin, H2 receptor antagonist and PPIs. (Appendix B)
6. If subjects are on anti-coagulant therapy during study participation
7. Receiving any drugs known to prolong the QT interval within 4 weeks prior to study or during the study
8. Known CNS metastasis.
9. History or presence of Thrombotic microangiopathy (TMA) or any other dermatological toxicity.
10. Subjects with ECOG Performance Status of > 2.
11. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
12. Surgical or other non-healing wounds.
13. Subjects with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
14. Subjects with current clinical or laboratory evidence of active infection.
15. History of other malignancies in the last 5 years
16. Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents. Exceptions are alopecia (any grade is acceptable), Hemoglobin greater than or equal to 9.0 g/dL, fatigue (Grade 2 is acceptable), and peripheral neuropathy (stable Grade 2 is acceptable) (As per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], V5.0).
17. If subjects found positive in alcohol breath test
18. If subjects found positive in urine screen for drugs of abuse
19. Participation in any clinical study within 90 days before the first dose of Investigational Product.
20. Loss of greater than or equal to 350mL (1 unit) of blood within 90 days before enrollment in the study.
21. Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subjects to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
22. Lactating women.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence and characterize the pharmacokinetic profiles of Pazopanib HCl 200mg Tablets of Torrent Pharmaceuticals Ltd., India compared to VOTRIENT® (Pazopanib HCl 200 mg) Tablets of Novartis Pharmaceuticals Corporation.
A total of twenty six (26) blood PK blood samples of 3.0 mL from each subject will be collected during the study duration. Sample 1:Day 26&34-Pre-dose blood sample (-48.00) hours,Sample 2: Day 17&35-Pre-dose blood sample (0.00) hours(within 5 minutes prior to dosing),Sample 3to12: Pre-dose blood sample (0.00) hours,0.50hrs, 1.00hrs,02.00hrs,03.00hrs,04.00hrs,05.00hrs,06.00hrs,08.00hrs,12.00hrs(± 05 minutes),Sample 13:Day19&37-24.00 hours(Within 5 minutes prior to next dose of IP administration)
Secondary Outcome
Outcome
TimePoints
To assess the safety of Pazopanib HCl 200mg Tablets of Torrent Pharmaceuticals Ltd., India in subjects with Advanced Renal cell Carcinoma.
A total of twenty six (26) blood PK blood samples of 3.0 mL from each subject will be collected during the study duration. Sample 1:Day 26&34-Pre-dose blood sample (-48.00) hours,Sample 2: Day 17&35-Pre-dose blood sample (0.00) hours(within 5 minutes prior to dosing),Sample 3to12: Pre-dose blood sample (0.00) hours,0.50hrs, 1.00hrs,02.00hrs,03.00hrs,04.00hrs,05.00hrs,06.00hrs,08.00hrs,12.00hrs(± 05 minutes),Sample 13:Day19&37-24.00 hours(Within 5 minutes prior to next dose of IP administration)
Target Sample Size
Total Sample Size="70" Sample Size from India="70" Final Enrollment numbers achieved (Total)= "61" Final Enrollment numbers achieved (India)="61"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is a
randomized, open label, multi-center, two-treatment, two-period, two-sequence,
two-way cross-over, multiple dose, steady-state Bioequivalence (BE) study of
Pazopanib HCl 200mg Tablets at a dose of 800 mg (4 * 200 mg tablets) of Torrent
Pharmaceuticals Ltd., India with VOTRIENT® (Pazopanib HCl 200mg) Tablets at a
dose of 800 mg (4 * 200 mg tablets) of Novartis Pharmaceuticals Corporation,
USA in subjects with Advanced renal cell carcinoma under fasting condition.
The primary
objective of this is to evaluate bioequivalence of Pazopanib HCl 200mg Tablets
of Torrent Pharmaceuticals Ltd., India compared to VOTRIENT® (Pazopanib HCl
200mg) Tablets of Novartis Pharmaceuticals Corporation, in subjects with
Advanced renal cell carcinoma under fasting condition.
"This syudy will be managed by CBCC Global research in agreement with sponsor (Torrent Pharmaceuticals Ltd., India)"