CTRI/2016/02/006674 [Registered on: 23/02/2016] Trial Registered Prospectively
Last Modified On:
23/08/2016
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of Everolimus 10mg in advanced renal cell carcinoma patients.
Scientific Title of Study
A randomized, multi center, open label, two-treatment, two-period, two-sequence, multiple dose, crossover, pivotal steady state bioequivalence study of Everolimus 10 mg tablet, Manufactured by Teva Pharmaceuticals - Pliva Croatia Ltd., Prilaz baruna Filipovica 25, 10000 Zagreb Croatia vs. Afinitor®(Everolimus) 10 mg tablet of Novartis Pharmaceuticals Corporation, USA in advanced renal cell carcinoma (RCC) patients under fasting conditions.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
15-VIN-284 Version 03 Date 16-Oct-2015
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Ashoka Kumar Singh
Designation
Head Of the Department, Clinical Operations
Affiliation
Veeda Clinical Research Pvt. Ltd.
Address
Veeda Clinical Research Pvt. Ltd. Shivalik Plaza A, Near IIM, Ambawadi, Ahmedabad
NA Ahmadabad GUJARAT 380015 India
Phone
07930013000
Fax
Email
Ashoka.Singh@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Yogesh Patel
Designation
Senior Manager-Clinical Operations
Affiliation
Veeda Clinical Research Pvt. Ltd
Address
Veeda Clinical Research Pvt. Ltd,
Shivalik Plaza-A, Near IIM,
Ambawadi, Ahmedabad NA Ahmadabad GUJARAT 380015 India
Phone
079-30013000
Fax
Email
Yogesh.AP@veedacr.com
Details of Contact Person Public Query
Name
Dr Yogesh Patel
Designation
Senior Manager-Clinical Operations
Affiliation
Veeda Clinical Research Pvt. Ltd
Address
Veeda Clinical Research Pvt. Ltd,
Shivalik Plaza-A, Near IIM,
Ambawadi, Ahmedabad NA Dohad GUJARAT 380015 India
Netaji Subhash Chandra Bose cancer research institute
Department of Oncology, Netaji Subhash Chandra Bose cancer research institute, 16 A, Park lane, Kolkata 700016, West Bengal, India. Kolkata WEST BENGAL
Afinitor® (Everolimus) tablets, 10 mg Manufactured by: Novartis Pharma Stein AG
Stein, Switzerland and
Distributed by: Novartis
Pharmaceuticals Corporation,
East Hanover, New Jersey
07936.
As per the randomization
schedule, either test [T] or [R] product will be administered orally to each patient (once daily) for 14 days in each period.
Dose: 10mg
Frequency: Once daily
Route of administration: Orally and
TOTAL duration of therapy: 28 days (14 days of each period).
Intervention
Everolimus tablets, 10 mg of Teva Pharmaceuticals USA.
As per the randomization schedule, either test [T] or [R] product will be administered orally to each patient (once daily) for 14 days in each period.
As per the randomization
schedule, either test [T] or [R] product will be administered orally to each patient (once daily) for 14 days in each period.
Dose: 10mg
Frequency: Once daily
Route of administration: Orally and
TOTAL duration of therapy: 28 days (14 days of each period).
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. Who are already receiving a stable dose of Everolimus tablets, 10 mg tablet once daily as per investigator’s discretion for at least 14 days at first dosing of study drug.
ExclusionCriteria
Details
1. Known hypersensitivity to rapamycin, everolimus or any excipient of everolimus.
2. Any prior treatment with everolimus resulting in unacceptable toxicity.
3. Receipt of any type of small molecule kinase inhibitors (i.e. axitinib, pazopanib, sorafenib, sunitinib etc) within 2 weeks before randomization.
4. Patients with renal failure, hepatic failure or for whom the need for dose change during the study can be anticipated.
5. Known brain metastasis, spinal cord compression, or carcinomatous meningitis; or evidence of brain or leptomeningeal disease on screening computed tomography or magnetic resonance imaging scan. (Unless adequately
treated with radiotherapy and/or surgery and stable for at least 3 months before randomization and neurologically asymptomatic at check in).
6. Pregnant and lactating females.
7. 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.
8. Participation in another clinical trial in the last 60 days.
9.History of noncompliance to medical regimens.
10. History of alcoholism / alcohol abuse.
11. History of difficulty with donating blood or difficulty in accessibility of veins.
12. Patients for whom oral administration of drug is not possible.
13. 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
Computer generated randomization
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare and evaluate the bioequivalence of Everolimus 10 mg tablet, Manufactured by Teva Pharmaceuticals - Pliva Croatia Ltd., Prilaz baruna Filipovica 25, 10000 Zagreb Croatia vs. Afinitor® (Everolimus) 10 mg tablet of Novartis Pharmaceuticals Corporation, USA in adult advanced renal cell carcinoma patients who are already receiving the drug at a stable dose of 10 mg once a day as their individual therapy.
Total of 42 blood samples at time points, 3.0 ml at pre-dose blood sample(00.00)
within 5 minutes before dosing on Day 12, 13, 14, 26, 27 and 28 of the study. On day 14 & day 28 (the PK day), the post-dose blood samples of 3.0 mL each will be drawn at 0.25,
0.50,0.75, 1.00, 1.25, 1.50, 1.75,2.00,2.25,2.50,3.00, 3.50, 4.00, 6.00, 8.00, 12.00, 16.00 and 24.00 hrs following drug administration.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patient.
NA
Target Sample Size
Total Sample Size="78" Sample Size from India="78" 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)?
Brief Summary
Patients with confirmed diagnosis of advanced renal cell carcinoma who are candidates for everolimus therapy (10 mg once daily) and who fulfill the inclusion and exclusion criteria will be randomized in study. As per randomization schedule, patient will be administered either Test or Reference orally once daily for 14 days in the following treatment sequence i.e. either R & T or T & R in each period crossed over without washout period.