A randomized, open label, multi-center, two-treatment, four-period, two-sequence, full replicate crossover, multiple dose, steady state Bioequivalence (BE) study of Pazopanib Tablets at a dose of 800 mg (4*200 mg tablets) of Oncogen Pharma (Malaysia) Sdn. Bhd. with Votrient® (Pazopanib) Tablets at a dose of 800 mg (4*200 mg tablets) of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA in advanced renal cell carcinoma patients under fasting condition
Tosham Road, Near South Bypass Crossing, Hisar, Haryana - 125005 India Hisar HARYANA
9896539142
drlovenish@gmail.com
Dr Dhananjay Selukar
Government Medical College and Super Specialty Hospital
Near Tukdoji Square, Nagpur- 440009, Maharashtra, India Nagpur MAHARASHTRA
9225234197
Vazirgmc@Gmail.Com
Dr Vinay Kumar
GSVM Medical College
Dept Of Surgery GSVM Medical Collage SWAROOP NAGAR KANPUR 208002 Uttar Pradesh, India Kanpur Nagar UTTAR PRADESH
9660640989
Vinaysighkgmc99@Gmail.Com
Dr Bidisha Ghosh Naskar
Health point Hospital
21 Prannath Pandit Street, Opposite Lansdowne, Paddapukur, - 700025, Kolkata West Bengal, India. Kolkata WEST BENGAL
8420805454
bghoshn@gmail.com
Dr Suraj Pawar
Kolhapur Cancer Centre Pvt.Ltd.
R.S 238, Opp. Mayur Petrol Pump, Gokul Shirgaon, Kolhapur-416234, Maharashtra, India Kolhapur MAHARASHTRA
982014908
surajpawar@yahoo.co.in
Dr Viraj Vijay Borgaonkar
Krupamayi Hospitals,
Akshay, Opp. Youth Hostel, Near Baba Petrol Pump, Aurangabad-431001, Maharashtra ,India Aurangabad MAHARASHTRA
9673073555
viraj.oncosurg@gmail.com
Dr Koushik Chatterjee
Life Line Diagnostic Center Cum Nursing Home
4A WOOD Street, Kolkata-700016, West Bengal, India Kolkata WEST BENGAL
9874357580
Drkaushikchatterjee@Gmail.com
Dr Smitha C Saldanha
Nano Hospital
79, Sir M Visveswaraya Rd, Nyanappana Halli, Hulimavu, DLF City Road,Near Arekere Saibaba Temple, Bengaluru-560076. Karnataka, India Bangalore KARNATAKA
948052106
saldanhasmitha@gmail.com
DrNibedita Sen
Netaji Subhash Chandra Bose Cancer Hospital
3081. Nayabad New Garia, Near IB Bus stand,
Kolkata - 700094, West Bengal, India
Kolkata WEST BENGAL
8373804819
nibedita.doctor@gmail.com
Dr Minishi Jain
Nobel Hospital Pvt.Ltd
Magarpatta City Road, Pune-411013, Maharashtra, India. Pune MAHARASHTRA
(1) ICD-10 Condition: C649||Malignant neoplasm of unspecifiedkidney, except renal pelvis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Pazopanib 200 mg tablets at a dose of 800 mg (4 x 200 mg tablets) of Oncogen Pharma (Malaysia) Sdn. Bhd.
Dosage: 800 mg (4 x 200 mg tablets)
Frequency:once daily under fasting conditions
Route of Administration: Oral
Comparator Agent
VOTRIENT® (Pazopanib) Tablets at a dose of 800 mg (4 x 200 mg tablets) of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936,USA
Dosage: 800 mg (4 x 200 mg tablets)
Frequency:once daily under fasting conditions
Route of Administration: Oral
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Subjects will be considered eligible for the study based on the following criteria:
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements.
2. Subjects aged greater than18 years with BMI at least 17.00 calculated as weight in kg per height in m2.
3. Subjects with confirmed diagnosis of advanced renal cell carcinoma includes,
(a) Newly diagnosed subjects
OR
(b) Subjects who are already receiving stable dose of Pazopanib tablets of 800 mg per day for at least 15 days
OR
(c) Subjects with failure of first line treatment for advanced renal cell carcinoma and as per investigators discretion are eligible to receive Pazopanib tablets.
4. Subjects able to swallow and retain oral medication
5. Life expectancy of at least 3 months at the time of screening.
6. Acceptable hematology status:
a. Hemoglobin greater than or equal to 9.0 g per dL
b. Absolute neutrophil count (ANC) greater than or equal to 1500 cells per mm3
c. Platelet count greater than or equal to 100,000 cells per mm3
7. Acceptable liver function:
a. Alanine aminotransferase (ALT) less than or equal to 2 X ULN (less than or equal to 5 X ULN in case of liver metastasis)
b. Aspartate aminotransferase (AST) less than or equal to 2X ULN less than or equal to 5 X ULN in case of livermetastasis)
c. Bilirubin less than or equal to ULN
8. Subjects with Creatinine clearance greater than or equal to 30 mL per minute
9. Cardiac ejection fraction greater than or equal to 50 percent by echocardiogram (ECHO) 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 of child bearing potential with negative serum pregnancy test at screening and at Day 1.
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 from screening, 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 or intrauterine system
c. Double barrier method of contraception (Condom and occlusive cap or condom and spermicidal agent)
d. Female sterilization (surgical bilateral oophorectomy) or tubal ligation at least 6 weeks prior to study participation
e. Total abstinence, partial abstinence is not acceptable.
13. No history of addiction to any recreational drug or drug dependence or alcohol addiction.
ExclusionCriteria
Details
Subjects will be excluded from the study based on the following criteria:
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 with relevant pre-existing cardiac disease at the time of screening
4. Subjects found with major vascular disease, arterial thromboembolic event 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, strong inhibitors of P-gp or breast cancer resistance protein (BCRP); narrow therapeutic index drugs that are metabolized by CYP3A4, CYP2D6 or CYP2C8; simvastatin, H2 receptor antagonist and PPIs.(Appendix B)
6. Subjects who are receiving or are anticipated to receive anti-coagulant therapy during study participation
7. Receiving any drugs known to prolong the QT interval within 4 weeks prior to first IP administration or during the study
8. Known central nervous system (CNS) metastasis.
9. History or presence of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal hemorrhage in the past 6 months
10. History or presence of Thrombotic microangiopathy (TMA) or any other dermatological toxicity..
11. History or presence of gastrointestinal perforation or fistula
12. History or presence of Interstitial Lung Disease/Pneumonitis
13. History or presence of Posterior Reversible Encephalopathy Syndrome
14. Subjects who are at risk of TLS (e.g. rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration)
15. Subjects with ECOG Performance Status of > 2.
16. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
17. Surgical or other non-healing wounds.
18. Subjects with positive serology for Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human Immunodeficiency virus (HIV).
19. Subjects who tested positive for Coronavirus infection (COVID-19)
20. Subjects with current clinical or laboratory evidence of active infection.
21. History of other malignancies in the last 5 years
22. Have 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).
23. If subjects found positive in urine alcohol test
24. If subjects found positive in urine screen for drugs of abuse
25. Participation in any clinical study within 90 days before the first dose of Investigational Product.
26. Loss of greater than or equal to 350mL (1 unit) of blood within 90 days before enrollment in the study.
27. 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.
28. Lactating women
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate steady state bioequivalence of Pazopanib at a dosage of 800 mg (4x200 mg tablets) of Oncogen Pharma (Malaysia) Sdn. Bhd. compared to VOTRIENT® (Pazopanib) Tablets at a dose of 800 mg (4x200 mg tablets) of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA in Advanced renal cell carcinoma patients under fasting condition.
A total of fifty six (56) blood PK samples will be collected from each subject during the study participation at baseline, 00.50, 01.00, 01.50, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, 12:00 & 24 hours.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to assess the safety and tolerability in Advanced renal cell carcinoma patients under fasting condition.
A total of fifty six (56) blood PK samples will be collected from each subject during the study participation at baseline, 00.50, 01.00, 01.50, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, 12:00 & 24 hours.
Total Sample Size="44" Sample Size from India="44" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Oncogen
Pharma (Malaysia) Sdn. Bhd. has developed a generic product of the RLD
Votrient® (Pazopanib) tablets. Oncogen Pharma (Malaysia) Sdn. Bhd. wants to
conduct the study to characterize the pharmacokinetic profile of test product
in comparison to the reference product in subjects with advanced renal cell
carcinoma in order to assess steady state bioequivalence.
The
study has been designed at a dose of 800 mg (4 * 200 mg tablets) in line with
the applicable USFDA’s Guidance.