CTRI/2021/03/031750 [Registered on: 05/03/2021] Trial Registered Prospectively
Last Modified On:
07/06/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A clinical trial in Steady state Bioequivalence Study of Sunitinib Malate Capsules 50 mg with Sutent capsules 50 mg in adult patients with advanced renal cell carcinoma already receiving stable dose of Sunitinib Malate Capsules 50 mg under fasting conditions
Scientific Title of Study
A Multicentric Open label Randomized Two Period Two Treatment Two Sequence Crossover Multiple Dose Steady state Bioequivalence Study of Sunitinib Malate Capsules 50 mg of Eugia Pharma Specialities Limited India with Sutent capsules 50 mg of Pfizer Labs USA in adult patients with advanced renal cell carcinoma already receiving stable dose of Sunitinib Malate Capsules 50 mg under fasting conditions
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NIL
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
GSL Cancer trust, NH16, Lakshmi Puram, Rajahmundry, Andhra Pradesh-533296 East Godavari ANDHRA PRADESH
9491582201
drcdeepakresearch@gmail.com
Dr G Govindaraj
Harshamitra Oncology Hospital
Harshamitra Oncology Private Limited Trichy - Madurai Highway, Nagamangalam, Tamil Nadu 620012 Tiruchirappalli TAMIL NADU
737354777
govindarajganesan@gmail.com
Dr Vijaya Aditya Yadaraju
HCG Cancer Centre
HCG Cancer Centre (A Unit of
Healthcare Global Enterprises
Limited), Plot No 10, Survey
No 13P, APIIC Health City,
Chinagadili, Arilova,
Visakhapatnam 530040 Visakhapatnam ANDHRA PRADESH
8916682700
vijayaditya.y@hcgel.com
Dr Ajay Mehta
HCG NCHRI Cancer Centre
HCG NCHRI Cancer Centre
Near Aurototive Square
Kalamna Ring Road Nagpur 440026
Nagpur MAHARASHTRA
9823190192
drajay.mehta@hcgel.com
Dr Koushik Chatterjee
Health Point Hospital
Health Point Hospital, 21, Prannath Pandit Street, Opposite Lansdowne Padmapukur, Kolkata 700025 Kolkata WEST BENGAL
K R Hospital Mysore Medical
College Research Institute
Clinical Research Room Next
to NSB 12 2nd Floor New
Surgical Block Mysore
570001 Karnataka
Mysore KARNATAKA
9901000559
prakashyesyes@yahoo.com
Dr Suparna Kanti Pal
Life Line Diagnostic Centre Cum Nursing Home
Life Line Diagnostic Centre Cum Nursing Home
4A,Wood Street,
Kolkata - 700016,
West Bengal,
India.
Kolkata WEST BENGAL
9830576704
suparna.k.pal@gmail.com
Dr Wategaonkar Ravikumar Narayan
Lokmanya Holistic Cancer
Lokmanya Holistic Cancer
Care Research Centre
Lokamanya Hospital 314 B
Telco Road Chinchwad Pune
411033 Maharashtra
Pune MAHARASHTRA
Dr. Sameer Shrirangwar National Cancer Institute Khasara No. 25, Outer Hingna ring road, Mouza Jamtha, Nagpur-441108, Maharashtra,India
Nagpur MAHARASHTRA
9833633299
Dr.sameer.mdmed@gmail.com
Dr Tanmoy Mondal
Netaji Subhas Chandra Bose Cancer Hospital
Netaji Subhas Chandra Bose
Cancer Hospital 3081
Nayabad New Garia Kolkata
700094
Kolkata WEST BENGAL
9051238499
Tanmoy.nrs@gmail.com
Dr Jain Minish Mahendra
Noble Hospital Pvt. Ltd
Noble Hospital Pvt Ltd 153
Magarpatta City Road
Hadapsar Pune 411013
Pune MAHARASHTRA
Pulse Multispecialty Hospital
Sr No 51 7 B1 1st Floor
Vishwa Arcade Opp Deccan
Pavilion Hotel Mumbai
Bangalore Highway Narhe
Pune 411041 Pune MAHARASHTRA
9552265656
Ash127win@gmail.com
Dr Mukesh C Arya
S.P. Medical College & AG of Hospitals
Department of Urology, Uro-Science Centre Bikaner 334001, Rajasthan,India Bikaner RAJASTHAN
9414138782
mcarya@yahoo.com
Dr Bidisha Ghosh
Sengupta Hospital Developers and Solutions Private Limited
Sengupta Hospital Developers and Solutions Private Limited,4, Harimohan Dutta Road,
Dum Dum, Kolkata-700028 West Bengal
Kolkata WEST BENGAL
Shambhavi Centre for Cancer and Gynecology, Near Lalpur Chowk, Opposite Hotel Landmark, Ranchi, Jharkhand-834001 Ranchi JHARKHAND
7761848530
shambhavioncology@gmail.com
Dr V Arumugam
Shifa Hospital
82, Near Junction Flyover, Kailasapuram, Middle Street, Tirunelveli Junction, Meenakshipuram, Tirunelveli, Tamil Nadu 627001 Tirunelveli TAMIL NADU
9842913301
arumugamonco@gmail.com
Dr Mangesh Mekha
Shree Hospital
Shree Hospital, Kharadi 7/3/B, Gulmohar soc, near Rakshak Nagar Phase 1, Behind hotel Radisson, Pune, Maharashtra, India-411014 Pune MAHARASHTRA
8149364641
mangesh.mekha@gmail.com
Dr Manjunath
Sri Laxmi Super Specialty Hospital
Sri Laxmi Super Specialty
Hospital No 5 6 7 1 st
Cross Kaggadasapura main
Rd Nagappareddy Layout C
V Raman Nagar Bengaluru 560093
Bangalore KARNATAKA
9562266843
manju.bmc@gmail.com
DrSangeetha Jiwatani
Sushrut Hospital & Research Centre
Sushrut Hospital & Research Centre. 365, Swastik Park, Chembur (East), Mumbai 400 071 Mumbai (Suburban) MAHARASHTRA
8097681981
sangeetajiwatani@hotmail.com
Dr Tanveer Maksud
Unique Hospital Multispeciality and Research Institute
Unique Hospital Multispeciality and Research Institute
Opp. Kiran Motor, Near Canal, Civil Char rasta, Sosyo Circle Lane, Surat - 395002, Gujarat, India.
Surat GUJARAT
(1) ICD-10 Condition: C649||Malignant neoplasm of unspecifiedkidney, except renal pelvis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Sunitinib Malate Capsules 50 mg
The study will consist of multicentric and eligible Subjects as per randomization are required to receive the Sunitinib Malate Capsules Once daily for 14 days (for eg on Study Days 1 to 14)
Comparator Agent
Sutent® capsules 50 mg
The study will consist of multicentric and eligible Subjects as per randomization are required to receive the Sutent® capsules 50 mg once daily for 14 days (for eg on Study Days 15 to 28) with food
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Male and or female patient of age in between 18 years to 65 years (both inclusive)
Patient with confirmed diagnosis of advanced renal cell carcinoma (histological or radiological)
Patient who are already receiving a stable dose of Sunitinib Malate Capsules 50 mg once daily as per investigators discretion for at least 14 days at screening
Patient with ECOG (Eastern Cooperative Oncology Group) performance status 0 2
Patient with estimated life expectancy greater than equal to 3 months
Patient should have no clinically significant abnormality in any of the laboratory parameters including ECG and Chest X ray as per the discretion of Principal Investigator at screening only
Patient with no persistent toxicities from prior medications Recovery to baseline or lesser tha equal to Grade 1 CTCAE v 5 0 or higher and or stable on supportive therapy at screening visit if any toxicities had occurred unless the toxicities were clinically insignificant
Patient with adequate organ and bone marrow function based upon the following laboratory criteria at the time of screening
Hemoglobin greater than equal to 9 g per dL
Absolute neutrophil count greater than equal to 1500 per uL
Platelet count greater than equal to 100000 per uL
Creatinine lesser than 2 x ULN
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) lesser than 2.5 x upper limit of normal
Total bilirubin within lesser than equal to 1.5 x upper limit of normal
Clinically insignificant fasting serum glucose levels, S. blood urea nitrogen (BUN) and Urine protein levels
Patient and/or Legally Acceptable Representative had given consent after being advised of the nature and risks of the study
Female patient of childbearing potential must have a negative serum pregnancy test at screening
Females must use acceptable and effective methods of contraception during the study conduct and up to 8 weeks after last does of study drug such as the following:
Tubal sterilization (tubal ligation performed more than one month before Study Day 1 transcervical tubal occlusion procedure performed more than six months before Study Day 1)
Intrauterine Device (IUD)
Progestin Implant (i e Implanon or its equivalent)
Progestin injection or progestin oral contraceptive pill and one barrier method (cervical cap diaphragm, contraceptive sponge or vaginal spermicide and a male or female condom)
Two barrier methods used together (cervical cap, diaphragm contraceptive sponge, or vaginal spermicide and a male or female condom)
Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner) during the study conduct
Male patient must agree to use an effective method of contraception from screening during study and up to 8 weeks after the last dose of study drug
Patient willing to and able to comply with the protocol
ExclusionCriteria
Details
Patient who are hypersensitive to Sunitinib and its excipients
Patient with hypertension (BP greater than equal to 150 per 100 mm of Hg even after use of more than 1 antihypertensive medication) and cardiac risk factors (e g known congestive heart failure low left ventricular ejection fraction or prolonged QT interval)
Patient with hepatic or renal dysfunction as per Investigators Discretion
Patient with diagnosis of any second malignancy within the last 5 years except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
Patient with history of or known brain metastases, spinal cord compression, or carcinomatous meningitis or past history of brain or leptomeningeal disease
Patient with history of pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
Patient with major surgery or radiation therapy lesser than 4 weeks of starting the study treatment
Patient with severe acute or chronic medical psychiatric condition that could have increased the risk associated with study participation study drug administration or interpretation of study results in the judgment of the investigator
Patient who require invasive dental procedures
Patient with uncontrolled diabetes as per investigators discretion
Patient with history of arterial thrombosis or deep vein thrombosis within the past 12 months
Patient within the 6 months prior to study drug administration
severe unstable angina
symptomatic congestive heart failure or
cerebrovascular accident
Patient with ongoing cardiac dysrhythmias:
atrial fibrillation of any grade or
QTc interval prolongation to lesser than 500 msec for males or lesser than 470 msec for females
Patient with positive test for hepatitis B surface antigen hepatitis C antibody or human immunodeficiency virus (HIV) 1 and 2 serological test at screening or has been previously treated for hepatitis B hepatitis C or HIV infection
Patient with positive test for urine drugs of abuse and or alcohol breath test
Patient with history of noncompliance to medical regimens
Patient with history of alcoholism alcohol abuse
Patient with history of difficulty with donating blood or difficulty in accessibility of veins
Patient for whom oral administration of drug is not possible
Patient with an unusual or abnormal diet for whatever reason within 48 hours prior to check in e g religious fasting
Consumption of grapefruit mosumbi sweet lime juice within 48 hours prior to study check in and for the entire period of study
Patient donated blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study
Patient participated in another clinical trial in the last 60 days
Pregnant and lactating females
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Area under the plasma concentration time curve over the steady state dosing interval
Maximum plasma concentration over the steady state dosing interval
pre-dose blood samples collected on 1, 12, 13 and 14 in
Period I and on Day 26, 27 and 28 in Period II. Post dose
samples 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20 and 24 hours post
morning dose on Day 14 and Day 28
Secondary Outcome
Outcome
TimePoints
Minimum plasma concentration over the steady state dosing interval.
Average plasma concentration over the steady state dosing interval.
Percentage fluctuation:
• Time of maximum measured plasma concentration over the steady state dosing interval.
• Cpd (pre-dose concentration)-Pre-dose concentrations determined before a dose at steady state.
• Swing
Safety and tolerability
pre-dose blood samples collected on 1, 12, 13 and 14 in
Period I and on Day 26, 27 and 28 in Period II. Post dose
samples 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20 and 24 hours post
morning dose on Day 14 and Day 28
Target Sample Size
Total Sample Size="52" Sample Size from India="52" Final Enrollment numbers achieved (Total)= "48" Final Enrollment numbers achieved (India)="48"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Patients meeting all inclusion and none of the exclusion criteria will be randomized on Day 0. Patients will be randomized to either Test or Reference product of Sunitinib Malate Capsules 50 mg once daily from Day 1 to Day 14 and alternate study treatment as per randomization on Day 15 to Day 28 without washout period. On Day 1, patients will be provided with a diary card to enter the details of study drug consumption at his/ her home On Day 1, patients will be administered one capsule of investigational medicinal product as per randomization schedule at the clinic with 240 mL of drinking water at room temperature. Dosing time on day 1 will be recorded on patient diary and patients will be instructed to follow the same dosing time each day and dosing time will be recorded on the study diary. On Day 1, patients will be provided with sufficient quantity of Investigational medicinal products for dosing at his/ her home from day 2 to day 7. Patient will be requested to come to the clinical facility on day 6 (± 1 day). On Day 6 (± 1 day), patient will be provided with sufficient quantity of Investigational medicinal products for dosing at home from next day to day 11 and patients diary card will be checked for dosing compliance and any adverse event and then the diary card will be handed over to patient again. On Day 11 patients will be required to visit the clinical facility for housing in the subsequent days. Patients shall fast overnight for at least 10.00 hours prior to dosing and should fast for 4.00 hours post dose on Day 14. Water will not be allowed for 1.00-hour pre dose and 1.00-hour post dose on Day 14. During their stay in the clinical facility on Day 12, 13 & 14, subject will be administered the investigational drug at the scheduled time of dosing. Venous blood samples (~4 mL) will be withdrawn within 5 minutes prior to dosing on Day 1, 12, 13 and 14. The pre-dose blood samples will be collected on Day 12, 13 and 14 in Period-I to confirm achievement of steady-state. Pre dose blood sample on day 1 is collected to confirm that patients are on stable dose of Sunitinib capsules. Day 14: On the day of complete pharmacokinetic sampling the post dose venous blood samples (~4 mL) will be withdrawn at 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00, 10.00, 11.00, 12.00, 14.00, 16.00, 20.00 and 24.00 hours post dose administration. All post dose samples will be collected within ± 2 minutes of scheduled time till 9.00 hrs post dose and from 10.00 hrs to 20.00 hrs post dose ± 10 minutes will be allowed. Last sample (i.e. 24.00 hours post dose) on day 15 will be collected within 10 minutes prior to schedule time. Patients will be crossed over to other investigational product (allocated as per randomization schedule) on Day 15, after the last PK sample collection in period-I. Patients will take their first dose of period II on Day 15 at the clinic with 240 mL of drinking water at room temperature at the same time as they take their medications during period I and will be subsequently discharged after they are provided with sufficient quantity of Investigational medicinal products for dosing at his/her home from day 16 to day 21. Dosing time on day 15 will be recorded on patient diary and patients will be instructed to follow the same dosing time (a time window of ± 30 minutes is allowed) each day and dosing time will be recorded on the study diary. Patient will be requested to come to the clinical facility on day 20 (± 1 day) and will be provided with sufficient quantity of Investigational medicinal products for dosing at home from next day to day 25 and patients diary card will be checked for dosing compliance and any adverse event and then the diary card handed over to patient again. On day 25, patients will be required to visit the clinical facility for housing in the subsequent days. During their stay in the clinical facility on Day 26, 27 & 28, patients will be administered the investigational drug at the scheduled time of dosing. Patients shall fast overnight for at least 10.00 hours prior to dosing and should fast for 4.00 hours post dose on Day 28. Water will not be allowed for 1.00-hour pre dose and 1.00-hour post dose on Day 28. Pre-dose blood sample (~4 mL) will be collected within 5 minutes before dosing on Day 26, 27 and 28 to confirm steady state. Day 28 :On the day of complete pharmacokinetic sampling the post dose venous blood samples (~4 mL) will be withdrawn at 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00, 10.00, 11.00, 12.00, 14.00, 16.00, 20.00 and 24.00 hours post dose administration. End of Study assessments will be performed after the last sample is collected on day 29 in Period II and then patient will be discharged from the clinical facility.