Comparative BE study of Everolimus 10 mg tablet OD manufactured by Par Pharmaceutical,NY 10977,USA with Afinitor10 mg tablet manufactured by Novartis Pharma Stein AG Stein, Switzerland in Advanced Renal Cell Carcinoma patients under fasting condition.
Scientific Title of Study
A Multicenter, randomized, open label, two treatment, two period, two sequence, multiple-dose, cross-over, bioequivalence study of Everolimus 10 mg tablet once daily manufactured by Par Pharmaceutical, Inc. 1 Ram Ridge Road, Spring Valley, NY 10977,USA with Afinitor (Everolimus) 10 mg tablet manufactured by: Novartis Pharma Stein AG Stein, Switzerland and Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 in Advanced Renal Cell Carcinoma patients under fasting condition
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
13-VIN-537 study protocol version 01 dated 20-Dec-2013
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Veeda clinical research Pvt. Ltd Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad 380 015, India
Countries of Recruitment
India
Sites of Study
No of Sites = 31
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Senapati Surendranath
Acharya Harihar Regional Cancer Centre ,
Department of Radiation Oncology, Medical Road, Mangalabag, Cuttac, Odisha Cuttack ORISSA
9437031718
snsenapati2007@gmail.com
Dr Kaustubh Kulakarni
Aster Aadhar Hospital (Prerana Hospital Ltd.)
Department of Surgery, Near Shashtri Nagar, KMT Workshop, Kolhapur, Maharashtra-416012 Kolhapur MAHARASHTRA
9225068540
kkulkarni.aacr@gmai.com
Dr Shankar Mahadev
Axon Hospital
Axon Hospital,Third Floor, Clinical Research department, Ameerpet road,
Opposite ICICI bank
Hyderabad, Andhra Pradesh -500 038
Hyderabad ANDHRA PRADESH
9848050717
drdoddala@gmail.com
Dr Jadhav
B. J .Government Medical College and Sassoon
First Floor, Department of Surgery, Ward no. 10, Sassoon Road, Somwar Peth,
Pune, 41 1001, Maharashtra, India Pune MAHARASHTRA
02026128219
drkirankumarj@gmail.com
Dr A V S Suresh
BIBI General Hospital & Cancer center
Third Floor, Clinical Research, 16-3-991/1/c,
Govt Printing press road,
Malakpet, Hyderabad, 500024, AP, India Hyderabad ANDHRA PRADESH
9246243024
sureshattili@yahoo.com
Dr Shailesh Shah
Bodyline Hospital
Research Room, Ground Floor, Opp. Anupama Hall, Near Dev Status, New Vikas Gruh Road,
Paldi, Ahmedabad-380007, Gujarat, India
Ahmadabad GUJARAT
9824035673
shaileshshahuro@yahoo.co.in
Dr Ajay Mehta
Central India Cancer Research Institute
Ground floor, Clinical Research Department, 11, Shankr Nagar,
West High Court, Nagpur, 440010 Maharastra Nagpur MAHARASHTRA
9823190192
ajayonco@hotmail.com
Dr Gopichand
City Cancer centre
First Floor, Clinical Research Department, 33-25-33, Venkta Krishnayya street suryaraopet, Vijaywada-520002 Hyderabad ANDHRA PRADESH
9885256059
mgopichand@yahoo.com
Dr Rajneesh Nagarkar
Curie Manavata cancer centre
Oncology OPD, Ground Floor,Opp:Mhamarg Bus Stand,Mumabi,Nasik, Maharastara-422002,INDIA. Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr K N Srinivasan
Dr. G Vishwanathan Speciality Hospital
Oncology OPD, Ground Floor, No. 27, Babu Road,
Trichy-620008, Tamilnadu
Tiruchirappalli TAMIL NADU
9443337230
kns68@yahoo.com
Dr Arun
Dr. GVN Cancer Institute,
Department of Medical Oncology, No. 46 Singaralhope, Trichy-620008, Tamil Nadu, India Tiruchirappalli TAMIL NADU
9286220191
aurunonco@gmail.com
Dr K Velavan
Erode Cancer Centre
Erode Cancer Centre, Velavan Nagar,
(Near Chinthamani petrol punk)
Thindal (PO), Peruindurai Road, Erode-638012 Erode TAMIL NADU
9842334222
velavandoctor@gmail.com
Dr Ranjan Mahoprata
Global Hospital and Health city
Departement of Medical Oncology, # 439, Cheran nagar, Perumbakkam,
Chennai - 600100 Chennai TAMIL NADU
9840033512
reanpv60@hotmail.com
Dr M Kamble
Government Medical College and Hospital
Department of Radiation therapy and Oncology, Room No. 85,
Vishwakarma Nagar, Nagpur-440003, Maharashtra, India
Nagpur MAHARASHTRA
9850246275
drkmkamble@yahoo.co.in
Dr Raghunath SK
HCG Bangalore Institute of Oncology
HCG tower No. 4 , Fifth Floor,Room No. 512, Lane No. 8, P. Kalinga Rao road,
Sampangiram Nagar, Bangalore – 560027, Karnataka , India Bangalore KARNATAKA
9731209671
drraghunathsk@yahoo.com
Inamdar multispecialty Hospital
Inamdar multispecialty Hospital
Hospital Building ,Basement, Research Room, S.No. 15 Fatima nagar, Pune , Maharastra 411040, India Pune MAHARASHTRA
020-41236660
drtusharp@gmail.com
Dr Ravindra Deshmukh
Jasleen Hospital
Kidney Centre, Panchsheel Square, Wardha Road, Nagpur-440012, Maharashtra, India Nagpur MAHARASHTRA
9823056120
drravi1962@gmail.com
Dr Rakesh Neve
Maharastra Medical Foundation Joshi Hospital
First Floor, Clinical Research Department, 778 opp. Kamala Nehru park, Pune – 411004, Maharastra India Pune MAHARASHTRA
020-25676861
drrakeshn@gmail.com
Dr Kirushna Kumar
Meenakshi mission hospital and research center,
Department of Oncology,Lake area,Merul road,
Madurai,Tamilnadu,
625107 Madurai TAMIL NADU
9787713004
drkskk@yahoo.com
Dr Mahesh Desai
Muljibhai Patel Society for Research in Nephro-Urology
Urology Ofice, Dr.Virendra Desai Road,
Nadiad-387-001, Gujarat, India
Kheda GUJARAT
9824028041
mrdesai@mpuh.org
Dr Mukesh
Mysore Medical College and Research Institute
Department of radiation Oncology, Irwin Road, Near Railway station, Mysore, 570001 Mysore KARNATAKA
9886873788
dal_muk@hotmail.com
Dr Bharat Rangarajan
Narayana Hrudayalaya Hospital
Department of Medical Oncology, Mazumdar Shaw Medical Centre,NH Health City, 7th Floor 258/A Bommasandra Industrial Area Anekal Taluk,
Bangalore - 560 099, Karnataka, India Bangalore KARNATAKA
9591970742
Bharath37@gmail.com
Dr Ketan Shukla
New Civil Hospital and B.J.Medical College
Department of Urology,
Asarwa, Ahmedabad-380016, Gujarat, India
Ahmadabad GUJARAT
9825097767
ketanshukla1968@gmail.com
Dr Minish Jain
Noble Hospital, Pvt ltd
Ground Floor, Clinical Research Room,153, Magarpatta city road,
Hadapsar, Pune 411013
Maharashtra , India Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr OP Sharma
S.M.S Medical College & Attached Hospital’s
Department of Radio-Oncology, J.L.N Marg, Jaipur- 302004 Jaipur RAJASTHAN
9829057033
omshar_2005@yahoo.co.in
Dr Vinay Tomar
S.M.S Medical College & Attached Hospital’s
Department of Urology, J.L.N Marg, Jaipur- 302004 Jaipur RAJASTHAN
9414057088
dr_v_tomar@yahoo.co.in
Dr Amit Bhatt
Sanjeevan Hospital
First Floor, Research Room No. 104, Plot No. 23, Opposite Karve Road, Erandawane, Pune-411004
Pune MAHARASHTRA
92215510913
drbamit.research@gmail.com
Dr CT Satheesh
Sri Venkateshwara Hospital
Third Floor, Clinical Research Department, No. 86 , Hosur Main road,
Madiwala, Bangalore, 560068
Bangalore KARNATAKA
9242698750
svhospitalresearch@gmail.com
Dr K C Lakshmia
Srinivasam cancer care hospitals India Pvt Ltd
Fourth Floor, Clinical Research Department, No 236/1, Vijayashree layout, Arekere, Bennerghatta main road, Bangalore, 560076 Bangalore KARNATAKA
Afinitor (Everolimus) 10 mg tablet, Once daily, Orally for 14 days
Manufactured by: Novartis Pharma Stein AG Stein, Switzerland and Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936
Intervention
Everolimus 10 mg tablet, Once daily, Orally for 14 days
Manufactured by Par Pharmaceutical, Inc. 1 Ram Ridge Road, Spring Valley, NY 10977,USA
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1.Men and Women, of age in between 18 years to 65 years (both inclusive).
2.Ability to provide informed consent prior to participation in the study
3.Histologically or Cytologically confirmed diagnosis of advanced renal cell carcinoma.
4.Women of childbearing potential must have a negative serum pregnancy test in screening and negative urine pregnancy test on day 0 and must be using an adequate method of contraception.
5.Patients with advanced renal cell carcinoma and who are already receiving a stable dose of Everolimus tablets, 10 mg tablet once daily.
6.Adequate organ function, defined as the following:
•Hemoglobin level ≥ 9 gm /dl
•Total bilirubin < 1.5 x upper limit of normal (ULN)
•SGOT and SGPT < 2.5 x ULN
•Creatinine < 1.5 x ULN
•Platelets > 100 x 10 raise to nine/L
•Clinically non significant fasting blood glucose levels
7.No history of addiction to any recreational drug or drug dependence
8.No participation in any clinical study within the past 60 days prior to first dosing in the study.
9.ECOG performance status of ≤ 2 on the ECOG scale
10.Clinically acceptable ECG in opinion of the Investigator/Designee.
ExclusionCriteria
Details
1.A history of allergic or adverse reactions to Everolimus or any other rapamycin derivative or any of its excipients
2.Patients with renal failure, or for whom the need for dose change during the study can be anticipated, should be excluded.
3.Patient with active infection and symptoms of Non-infectious pneumonitis (symptoms such as but not limited to hypoxia, pleural effusion, cough, or dyspnea, and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations) as judged by the investigator.
4.Concurrent use of other drugs known to suppress bone marrow function
5.Expected changes in concomitant medications during the period of study
6.Positive tests for drug of abuse at baseline.
7.History of alcoholism / alcohol abuse.
8.Patients who are:
•Pregnant
•Breast feeding
•Of childbearing potential without a negative pregnancy test at baseline
•Male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial and at least 8 week after ending study treatment.
9.Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery
10.Patients with known positivity for human immunodeficiency virus (HIV), HBsAg and HCV.
11.Patients with any significant history of non-compliance to medical regimens
12.History of difficulty with donating blood or difficulty in accessibility of veins.
13.Patients for whom oral administration of drug is not possible.
14.An unusual or abnormal diet, for whatever reason e.g. religious fasting.
15.Patients having known brain metastasis
16.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study.
Method of Generating Random Sequence
Other
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
•To compare and evaluate the multiple-dose oral bioavailability of Everolimus 10 mg tablet once daily manufactured by Par Pharmaceutical, Inc. 1 Ram Ridge Road, Spring Valley, NY 10977 USA, with Afinitor (Everolimus) 10 mg tablet manufactured by: Novartis Pharma Stein AG Stein, Switzerland and Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 in Advanced renal cell carcinoma patients under fasting condition.
The pre-dose blood sample of 3.0 mL (00.00) will be collected within 5 minutes before dosing on Day 12 and 14 of both periods. On day 14, the post-dose blood samples of 3.0mL each will be drawn at 0.25, 0.5,0.75, 1.0,2.5, 3.0, 4.0, 8.0, 12.0 and 24.0 hrs following drug administration in each period.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of Patient
Not Applicable
Target Sample Size
Total Sample Size="48" Sample Size from India="48" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
A Multicenter, randomized, open label, two treatment, two period, two sequence, multiple-dose, cross-over, bioequivalence study of Everolimus 10 mg tablet once daily manufactured by Par Pharmaceutical, Inc. 1 Ram Ridge Road, Spring Valley, NY 10977,USA with Afinitor (Everolimus)10 mg tabletmanufactured by: Novartis Pharma Stein AG Stein, Switzerland and Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 in Advanced Renal Cell Carcinoma patients under fasting condition. Sufficient number of patients will be enrolled to have 48 evaluable patients in the study . Total expected duration of the study will be of at least 29 days from the day first IMP administration in Period I till collection of last PK blood sample in period II i.e. on day 29 of the study. There will be a no washout period of betweentwo periods. For each patient, a total of 34 PK samples will be collected during the study. Patient will also be provided with a patient diary card to enter the details of study drug consumption at his/her home. Patient will be provided with adequate instructions to complete the patient diary card at his/her home.Compliance for dosing will be assessed by checking the patients diary for IMP consumption at home, pasting the duplicate label of dispensed container on the appropriate section of individual Case Report Form (CRF). Patients who complete the study and are withdrawn will have to go safety assessments immediately after the last IMP administration or last PK sample collection in period II. A telephonic safety follow up will be done for all the randomized patients till 30 days after the last IMP administration in the study.