CTRI/2020/12/029989 [Registered on: 23/12/2020] Trial Registered Prospectively
Last Modified On:
08/01/2022
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 Advanced Renal Cell Carcinoma patients.
Scientific Title of Study
A Randomized, Open-Label, Two Treatment, Two Period, Two Sequence, Steady-State Crossover Bioequivalence Study Of Pazopanib HCL 200 Mg Tablet (4 Tablets X 200 Mg) Of Alembic Pharmaceuticals Limited, India And Votrient (Pazopanib HCL) 200 Mg Tablets (4 Tablets X 200 Mg) Of Novartis Healthcare Pvt. Ltd., India, Administered Under Fasting Conditions In Patients With Advanced Renal Cell Carcinoma (RCC).
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
G7SYN/P-001/2020 Version 01 Amendment 01 dated 22-10-2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Ajay Alexander
Designation
Head Clinical Research
Affiliation
G7 Synergon Private Limited
Address
Department - Clinical Research,
1st floor, Investigator Room, No 537 9th Cross 5th main Tata Nagar
Sahakaranagar Post Bangalore Karnataka India
Bangalore
KARNATAKA
560092
India Bangalore KARNATAKA 560092 India
Phone
09916252529
Fax
Email
ajay.alexander@g7synergon.in
Details of Contact Person Scientific Query
Name
Dr D Sathish Kumar
Designation
Managing Director
Affiliation
G7 Synergon Private Limited
Address
Department - Management,
1st floor, QA Room, No 537 9th Cross 5th main Tata Nagar Sahakaranagar Post Bangalore Karnataka India
Bangalore
Bangalore KARNATAKA 560092 India
Phone
09677014651
Fax
Email
sathishkumar@g7synergon.in
Details of Contact Person Public Query
Name
Dr D Sathish Kumar
Designation
Managing Director
Affiliation
G7 Synergon Private Limited
Address
Department - Management,
1st floor, QA Room, No 537 9th Cross 5th main Tata Nagar Sahakaranagar Post Bangalore Karnataka India
Bangalore
Bangalore KARNATAKA 560092 India
Asian institute of Medical Sciences
Badkal flyover road, Sec-21A,
Faridabad-121001,
Haryana, India
Faridabad HARYANA
9971635572
drpraveenkb@yahoo.com
Dr Rajnish Vasant Nagarkar
HCG Manavata Cancer Centre
First Floor, Clinical Research Department,
HCG Manavata Cancer Centre,
Behind Shivang Auto Mumbai Naka Nashik
Nashik Maharashtra -422002
Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Tanawade Prasad Kashinath
Kolhapur Cancer centre Private Limited
Kolhapur Cancer centre Private Limited, R S 238, opposite Mayur petrol Pump, Gokul Shirgaon, Kolhapur-416234, Maharashtra, India Kolhapur MAHARASHTRA
9167975011
prasad0297@gmail.com
Dr Wategaonkar Ravikumar Narayan
Lifepoint Multispecialty Hospital
Clinical Research Department, Lifepoint Multispecialty Hospital, 145/1, Mumbai Bangalore Highway,Near Hotel Sayaji Wakad pune Pune Maharashtra – 411057 Pune MAHARASHTRA
9545496547
wategoankar.ravi@gmail.com
Dr Sharad Desai
Mahatma Gandhi Cancer hospital
Mahatma Gandhi
Cancer hospital, Near
Gulabrao Patil
Homeopathic Medical
College, Shaskiya Dudh
diary road,
Shivajinagar,
Miraj-416410,
Maharashtra, India Sangli MAHARASHTRA
Clinical Research Department, 12th F main Kaveri Nagar, Bommanahalli, Plot no 11 and 12, 12th F main Kaveri Nagar, Bommanahalli Bangalore KARNATAKA
9880585797
lkrajeev@gmail.com
Dr Ghanashyam Biswas
Sparsh Hospital and Critical Care P Ltd
Sparsh Hospital and Critical Care P Ltd, A 407,
Saheed Nagar, Bhubaneswar Bhubaneswar, Khordha Orissa - 751007
Khordha ORISSA
9937500878
drgbiswas@gmail.com
Dr Rakesh Suresh Neve
Sterling Multispeciality Hospital
Sector No 27, Near BHEL Chowk, Pradhikaran Nigdi, Haveli Pune MAHARASHTRA
9881143140
rakesh.neve@gmail.com
Dr Tanveer Maksud Mohibbhai
Unique Hospital – Multispecialty & Research Institute
Unique Hospital Multispecialty and Research Institute, Opp. Kiran Motor, Canal Road Civil Hospital, Char Rasta- Sosyo Circle Lane, Off Ring road, Surat Surat Surat Gujarat - 395002 Surat GUJARAT
Manavata Clinical Research Institute Ethics Committee
Approved
Navsanjeevani Hospital Ethic Committee
Not Applicable
Shettys Hospital Ethics Committee
Not Applicable
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 200 mg tablet of Alembic Pharmaceuticals Limited, India
Patients will be randomly assigned in a 1:1 ratio to receive either Alembic Pharmaceuticals Limited, India’s pazopanib 800 mg tablet (4×200 mg) or VOTRIENT® (pazopanib) 800 mg tablet (4×200 mg) of Novartis Healthcare Pvt. Ltd., India.once daily for 14 days in each period. On Day 15, patients will cross over to the other formulation as per randomization schedule for the next 14 days.
Comparator Agent
VOTRIENT® (pazopanib) 800 mg tablet (4×200 mg) of Novartis Healthcare Pvt. Ltd., India
Patients will be randomly assigned in a 1:1 ratio to receive either Alembic Pharmaceuticals Limited, India’s pazopanib 800 mg tablet (4×200 mg) or VOTRIENT® (pazopanib) 800 mg tablet (4×200 mg) of Novartis Healthcare Pvt. Ltd., India.once daily for 14 days in each period. On Day 15, patients will cross over to the other formulation as per randomization schedule for the next 14 days.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Male or non-pregnant female patients more than 18 years of age.
2. Patient willing to give written informed consent.
3. Documented diagnosis (histological confirmation) of advanced RCC patient.
4. Patient who are stable on a dose of 800 mg of pazopanib at least for the last 15 days.
5. Patient, who in the opinion of the Investigator has a life expectancy greater than or equal to 6 months from the time of the first dose.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
7. Patient whose organ and immune system functions are adequate as indicated by the following laboratory values or considered by the Investigator/sub-Investigator to be of no clinical significance.
Hematologic:
Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
Platelets ≥ 100 X 109/L
Hemoglobin ≥ 9.0 g/dL
Prothrombin Time (PT) ≤ 1.2 X ULN
International Normalized Ratio (INR) ≤ 1.2 X ULN
activated Partial Thromboplastin Time (aPTT) ≤ 1.2 X ULN
Hepatic:
Total bilirubin ≤ 1.5 X ULN
AST and ALT ≤ 2.0 X ULN
Renal:
Serum creatinine ≤ 2 mg/dL
Creatinine clearance ≥ 30 mL/min
8. Patient with cardiac ejection fraction within the normal range as measured by echocardiogram.
9. The patient must have a clinically acceptable 12-lead ECG at screening including QTc interval ≤ 480 msec.
10. Patient must have clinically acceptable results for all the screening parameters and investigations.
11. Able to swallow and retain orally administered medication.
12. Availability of patient for the entire study duration and willingness to adhere to protocol requirements as evidenced by written informed consent.
13. Female patient
a) of childbearing potential practicing an acceptable method of birth control such as sexual abstinence, (other than hormonal contraceptives) e.g. barrier method (diaphragm, condom, etc.); for the duration of the study as judged by the investigator(s)/study physician and agree to follow the same during treatment and for at least one week after their study participation is complete. The patient agrees to accept the risk that pregnancy could still result despite using birth control devices. OR
b) Postmenopausal for at least the past 12 months. OR
c) Surgically sterile (bilateral tubal ligation/bilateral oophorectomy/hysterectomy has been performed on the patient).
14. Male patient must agree to practice an acceptable method of birth control such as sexual abstinence, a barrier method of contraception (i.e. condom) for the duration of the study as judged by the investigator(s)/study physician and agree to follow the same treatment and for at least one week after treatment discontinuation of Pazopanib HCL therapy. The patient agrees to accept the risk that pregnancy in a female partner could still result despite using birth control devices
ExclusionCriteria
Details
1. Pregnant and lactating female.
2. Patient receiving any medications or substances that are strong inhibitors or inducers of the CYP450 enzyme.
3. Receiving any drugs known to prolong the QT interval within 4 weeks before the study or during the study.
4. Patient with any hematological, renal, neurological, or liver injury > Grade 3 toxicity during prior systemic therapy regimens.
5. Patient with brain metastases as confirmed by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI).
6. Patient with clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with the risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days before study treatment
• Malabsorption syndrome
• Major resection of the stomach or small bowel.
7. Any other significant medical comorbidities or intercurrent illnesses or infection may have an impact on patient safety and do not permit the dosing of Pazopanib HCL as determined by the Investigator.
8. Patient with uncontrolled hypertension while receiving appropriate medication (systolic blood pressure ≥ 150 mmHg and diastolic blood pressure ≥ 90 mmHg).
9. Patient with hypokalemia, hypomagnesemia, or long QT syndrome.
10. History of any one of the following cardiac conditions within the past 6 months;
11. Cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, coronary artery by-pass graft surgery, class III or IV congestive heart failure as (NYHA), serious cardiac arrhythmias, cerebrovascular accident, stroke (including transient ischemic attack), pulmonary embolism or untreated deep venous thrombosis.
12. Evidence of bleeding diathesis or coagulopathy.
13. Anticoagulant treatment with curative intent.
14. Alcohol dependence, alcohol abuse, or drug abuse or addiction with any recreational drug within the past year.
15. Patient who have consumed grapefruit, citrus fruits, and its products for 48 hours before first dosing or during the study.
16. Patient who have consumed any xanthine containing items (i.e. tea, coffee, cola drinks, or chocolate/coca, etc.) for 48 hours before first dosing or during the study.
17. Allergy or significant history of hypersensitivity or idiosyncratic reactions to study drug product or its excipients etc.
18. History of difficulty in swallowing.
19. Clinically assessed as having inadequate venous access for PK sampling.
20. Patient deemed uncooperative or non-compliant.
21. Patient who have shown positive results in urine alcohol test and/or urine drug screening test.
22. Significant abnormal 12 lead ECG, X-ray, and 2D-Echocardiography finding.
23. A positive result of HIV, HCV, RPR, and HBsAg.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
The primary objective of this study is to characterize the pharmacokinetic (PK) profile of the test formulation (pazopanib tablets 200 mg of Alembic Pharmaceuticals Limited, India.) relative to that of reference formulation (VOTRIENT® tablets 200 mg) in patients of advanced RCC who are tolerating a stable dose of Pazopanib tablets 800 mg once daily and to assess the bioequivalence after multiple dose administration under fasting condition.
Day 14 (Period I) and Day 28 (period II)
Secondary Outcome
Outcome
TimePoints
The secondary objective of this study is to evaluate the safety and tolerability of the patients exposed to the pazopanib tablets 200 mg in patients of advanced RCC.
Day 14 (Period I) and Day 28 (period II)
Target Sample Size
Total Sample Size="18" Sample Size from India="18" 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, multicentre, two
treatment, two-period, multiple-dose, steady-state, cross over bioequivalence
study with no washout between the two periods under fasting condition. Each
patient will be dosed for 28 consecutive days while on the study, receiving 14
days of each treatment as per the study randomization schedule
The Primary objective to assess the steady-state
bioequivalence between Pazopanib HCL
200 mg Tablet (4 tablets X 200 mg) of Alembic
Pharmaceuticals Limited, India and Votrient® (Pazopanib HCL) 200 mg tablets (4 tablets X 200 mg)
of Novartis Healthcare Pvt. Ltd., India, in
Advanced Renal Cell Carcinoma (RCC) patients and the Secondary Objective is to
monitor the safety of patients during the conduct of the study.