CTRI/2020/11/029079 [Registered on: 12/11/2020] Trial Registered Prospectively
Last Modified On:
04/05/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence (BE) 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 Crossover, Multiple Dose, Steady-State Bioequivalence (BE) Study of Pazopanib HCl 200mg Tablets at a Dose of 800 mg (4 x 200 mg tablets) of Lotus Pharmaceutical CO. Ltd., Taiwan 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.
Behind Shivang Auto,
Mumbai Naka,
Nashik-422002, Maharashtra, India.
Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Bidisha Ghosh Naskar
Health Point Hospital
21, Prannath Pandit Street (OPP: Lansdown Padmapukur, Kolkata-700025, West Bengal, India Kolkata WEST BENGAL
8420805457
bghoshn@gmail.com
Dr Vijay Bhargava
Jawaharlal Nehru Cancer Hospital and Research Centre
PB no 32, Cancer Hospital Road, Bhopal-462001, Madhya Pradesh, India Bhopal MADHYA PRADESH
9512965930
drvijaypriya14@gmail.com
Dr D Raghunadharao
KIMS ICON Hospital
D.No_32-11-02, Sheelanagar, BHPV Post, Visakhapatnam - 530012, Andhra Pradesh, India Visakhapatnam ANDHRA PRADESH
9246571537
rdigumarti@gmail.com
Dr Ashish Agrawal
Kiran Hospital Multi super specialty hospital and Research Centre
Nr. Sumul Dairy, Surat-395004, Gujarat, India. Surat GUJARAT
9824196710
onco.kh@gmail.com
Dr Ashish Joshi
Mumbai Oncocare Centre (Unit of Cellcure Cancer Centre Pvt Ltd)
2nd Floor, Majithia Apartments, Gods Gift Premises Co-Op. Society Ltd, S V Road, Vile Parle (W), Mumbai- 400056, Maharashtra, India. Mumbai MAHARASHTRA
9167009042
ashjoshi44@mocindia.co.in
Dr Sandeep Vithoba Ishi
NAMCO Charitable Trusts S S.G. S. Cancer Hospital
Plot No 30/1/1B/1 & 30/2/2C/2, Opp RTO office, Panchavati, Nashik-422004, Maharashtra, India. Nashik MAHARASHTRA
8655321807
dr.sandeepishi@gmail.com
Dr Ghanshyam Patel
Nirmal Hospital Pvt. Ltd.
Ring Road, Surat-395002, Gujarat, India Surat GUJARAT
9376913131
drgnpatelonco@gmail.com
Dr Minish Jain
Noble Hospital Pvt.Ltd
153, Magarpatta City Road,
Hadapsar, Pune-411013, Maharashtra, India.
Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr Mukesh C Arya
S P Medical College and AG of Hospitals
Dept. of Urology ,Uro-science Centre, Bikaner -334001,Rajasthan,India Bikaner RAJASTHAN
9414138782
mcarya@yahoo.com
Dr Faisal Rashid Guru
Sher –I-Kashmir Institute of Medical Sciences
Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar-190011, Jammu and Kashmir, India Srinagar JAMMU & KASHMIR
9717017022
faisal_guru@yahoo.com
Dr Ghanshyam Biswas
Sparsh Hospital and Critical Care (P) Ltd
4/407, Saheed Nagar, Bhubaneswar-751007, Odisha, India. Khordha ORISSA
9937500878
drgbiswas@gmail.com
Dr Rajeev Gupta
Sri Guru Ram Das Institute of Medical Science and Research
VPO Vallabh Mehta Road, Amritsar, Punjab-143006, India Amritsar PUNJAB
9781709615
drrajeevgupta01@gmail.com
DrPrashant Kumbhaj
Sri Ram Cancer and Specialty Centre
Sri Ram Cancer & Superspeciality Center RIICO Institutional Area Sitapura Tonk Road Jaipur-302022, Rajasthan India Jaipur RAJASTHAN
7869409560
drprashantkumbhaj@yahoo.com
Dr Ankit Patel
United Green Hospital
Green Atria, Beside Silver Park Society, In front of Sneh Sankul wadi, Anand Mahal Main Road, Adajan, Surat – 395009, Gujarat, India Surat GUJARAT
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements.
2. Subjects aged 18 to75 years (both inclusive) having Body Mass Index (BMI) at least 17.00 calculated where weight in kg and 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 HCl tablets of 800 mg per day for at least 4 weeks OR (c) Subjects with failure of first line treatment for advanced renal cell carcinoma and as per investigator’s discretion are eligible to receive Pazopanib HCl tablets.
4. Subject is 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. 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 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 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 condom 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 the time of randomization.
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
. 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. Subject 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.
6. If a subject is 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. A subject with ECOG Performance Status of > 2.
11. Major surgical procedure (including periodontal) within 28 days of study participation.
12. Surgical or other non-healing wounds.
13. A subject with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
14. A subject testing positive for Coronavirus infection (COVID-19).
15. A subject with current clinical or laboratory evidence of active infection.
16. History of other malignancies in the last 5 years.
17. 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).
18. Subject is positive in alcohol breath test.
19. Subject is positive in urine screen for drug abuse.
20. Participation in any clinical study within 90 days before enrollment in the study.
21. Loss of greater than or equal to 350mL (1 unit) of blood within 90 days before enrollment in the study.
22. 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. 23. Lactating women.
24. History of difficulty in accessibility of veins or intolerance to venipuncture.
25. Any food allergy, intolerance, restriction or special diet that, in the opinion of the investigator could contraindicate the subject’s participation in this study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate bioequivalence of Pazopanib HCl 800 mg (4 x 200 mg) tablets of Lotus Pharmaceutical CO. Ltd., Taiwan compared to VOTRIENT® at a dosage of 800 mg (4 x 200 mg) tablets of Novartis Pharmaceuticals Corporation USA, in subjects with advanced renal cell carcinoma under fasting condition.
Sample 1-Day:10 and 22-Pre-dose blood sample (-48.00) hours, Sample 2- Day:11 and 23-Pre-dose blood sample (-24.00) hours(within 1.00 hour prior to dosing), Sample 3to12-Day 12 and 24-00.50hrs,01.00hrs,02.00hrs,03.00hrs,04.00hrs,05.00hrs,06.00hrs,08.00hrs,12.00hrs(± 05 minutes), Sample 13-Day:13 and 25-24.00 hours(Within 5 minutes prior to next dose of IP administration)
Secondary Outcome
Outcome
TimePoints
To evaluate the safety and tolerability of Pazopanib HCl dosage of 800 mg (4 x 200 mg) tablets in subjects.
Sample 1-Day:10 and 22-Pre-dose blood sample (-48.00) hours, Sample 2- Day:11 and 23-Pre-dose blood sample (-24.00) hours(within 1.00 hour prior to dosing), Sample 3to12-Day 12 and 24-00.50hrs,01.00hrs,02.00hrs,03.00hrs,04.00hrs,05.00hrs,06.00hrs,08.00hrs,12.00hrs(± 05 minutes), Sample 13-Day:13 and 25-24.00 hours(Within 5 minutes prior to next dose of IP administration)
Target Sample Size
Total Sample Size="82" Sample Size from India="82" 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
This is a randomized, open label, multi-center, two-treatment, two-period, two-sequence, two-way crossover, multiple dose, steady-state bioequivalence (BE) study with pharmacokinetic endpoints in subjects with advanced renal cell carcinoma under fasting condition. The primary objective of the study is to evaluate bioequivalence of Pazopanib HCl 800 mg (4 x 200 mg) tablets of Lotus Pharmaceutical CO. Ltd., Taiwan compared to VOTRIENT® at a dosage of 800 mg (4 x 200 mg) tablets of Novartis Pharmaceuticals Corporation USA, in subjects with advanced renal cell carcinoma under fasting condition.