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CTRI Number  CTRI/2012/09/002951 [Registered on: 03/09/2012] Trial Registered Prospectively
Last Modified On: 21/11/2018
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Comparision of two Temozolomide 250 mg capsules in the patients with Glioblastoma Multiforme or Anaplastic Astrocytoma under fasting condition. 
Scientific Title of Study   A multicentre, randomized,open label,two-period, two-treatment,two-way crossover, bioequivalence study comparing Temozolomide capsules 250 mg (Manufactured by: Fresenius Kabi Oncology Limited, India) to the reference listed drug Temodal® (Temozolomide) Capsules 250 mg (Manufactured by: Orion Corporation, Orion Pharma Division, Turku, Finland, Distributed by Schering-Plough Products Pharmaceuticals Ltd.,Brazil) in Glioblastoma Multiforme or Anaplastic Astrocytoma patients under fasting condition. 
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
545-11; Version 01 Amendment 01 Dated 11 February 2013  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ashoka Kumar Singh  
Designation  Asst. Gen. Manager 
Affiliation  Lambda Therapeutic Research Ltd. 
Address  Near Gujarat High court,S.G. Highway, Gota,

Ahmadabad
GUJARAT
380061
India 
Phone  09811126123  
Fax    
Email  ashokakumar@lambda-cro.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Ankit Ranpura 
Designation  Asst. Manager 
Affiliation  Lambda Therapeutic Research Ltd. 
Address  Near Gujarat High court,S.G. Highway,Gota,

Ahmadabad
GUJARAT
380061
India 
Phone  07940202074  
Fax  07940202021  
Email  ankitranpura@lambda-cro.com  
 
Details of Contact Person
Public Query
 
Name  Dr Praveen Shetty 
Designation  Manager 
Affiliation  Lambda Therapeutic Research Ltd. 
Address  Near Gujarat High court,S. G. Highway,Gota,

Ahmadabad
GUJARAT
380061
India 
Phone  07940202098  
Fax  07940202021  
Email  praveenshetty@lambda-cro.com  
 
Source of Monetary or Material Support  
Fresenius Kabi Oncology Ltd.Gurgaon-122001, Haryana, India. 
 
Primary Sponsor  
Name  Fresenius Kabi Oncology Ltd 
Address  Echelon Institutional Area, Plot No. 11, Sector-32,Gurgaon-122001,Haryana,India. 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 13  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Senapati  Acharya Harihar Regional Cancer Centre  Dept. of Radiation Oncology Acharya Harihar Regional Cancer Centre, Medical Road, Mangalabag, Cuttack-753 007
Cuttack
ORISSA 
9437031718

snsenapati2007@gmail.com 
Dr Rama Krishna  Axon Hospital  Axon hospitals, 8-3-215, srinivasanagar, colony (west) SR nagar, Ameerpet, Hyderabad-38
Hyderabad
ANDHRA PRADESH 
9849030979

rkmalladi@yahoo.com 
Dr Sandeep Madhwapathy  Belgaum Cancer Hospital  Belgaum Cancer Hospital, 9666-A2/D, Ashok Nagar, Belgaum- 590016, Karnataka, India
Belgaum
KARNATAKA 
9844033384

bch_belgaum@rediffmail.com 
Dr VSatya Suresh Attili  BIBI General Hospital & Cancer Centre  BIBI General Hospital & Cancer Centre, 16-3-991/1/C, Government Printing Press Road, Malakpet, Hyderabad-500024, Andhra Pradesh, India
Hyderabad
ANDHRA PRADESH 
9246243034

sureshattili@yahoo.com 
Dr Rakesh Taran  CHL-Apollo Hospitals  Dept. of Medical Oncology CHL-Hospital, Near LIG triangle, A.B.Road,Indore-452 008
Indore
MADHYA PRADESH 
9009779517

rakeshtaran@yahoo.com 
Dr Gopichand  City cancer centre  City cancer centre, #33-25-33, Ch. Venkata Krishnayya street, Suryaro pet, Vijaywada,Andhrapradesh-520 002
Krishna
ANDHRA PRADESH 
9885256059

mgopichand@yahoo.com 
Dr Shailesh Shende  Deenanath Mangeshkar Hospital and Research Centre  Deenanath Mangeshkar Hospital and Research Centre, Erandwane, Pune-411044, Maharashtra, India
Pune
MAHARASHTRA 
9890609830

shaileshshende@rediffmail.com 
Dr Kartar Singh  Green City Hospital  Green City Hospital, Near Dhantoli Police Station, Mehadia Square, Dhantoli, Nagpur-440012
Nagpur
MAHARASHTRA 
9890354174

drkartarsingh@yahoo.com 
Dr S P Shrivastav  Lions Cancer Detection Centre  Lions Cancer Detection Centre, New Civil Hospital Campus, Majura Gate, Surat – 395001, Gujarat, India
Surat
GUJARAT 
9824196710

liononco@gmail.com 
Dr Rajeev AG  M.S.Ramaiah medical college and Hospital  Dept. of Radiation Oncology M.S.Ramaiah medical college and hospital, MSRIT Post, New BEL Road, Bangalore - 560 054.
Bangalore
KARNATAKA 
9844345999

drrajeevag@yahoo.com 
Dr Kirushna Kumar  Meenakshi mission hospital and research centre  Dept. of Radiation Oncology Meenakshi Mission Hospital and Research Centre, Lake Area, Melur Road, Madurai- 625 107.
Madurai
TAMIL NADU 
9842113003

drkskk@yahoo.com 
Dr J K Singh  S S Hospital  Dept. of Radiation Oncology S S Hospital, Malahi Pakri Chowk, Doctors Colony, Kankarbagh, Patna- 800020.
Patna
BIHAR 
9006330804

drjksingh147@hotmail.com 
Dr Tushar Patil  Sahyadri Speciality Hospital  Dept. of Medical Oncology Sahyadri Speciality Hospital, Eraldwane, Karve Road, Pune-411004
Pune
MAHARASHTRA 
9552522556

tussipats@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 13  
Name of Committee  Approval Status 
AHRCC Institutional Ethics committee, Cuttack, Odisha  Approved 
Axon Institutional Ethics Committee, Hyderabad, Andhra Pradesh, India   Approved 
CHL-Apollo Hospitals-Ethics Committee, Indore, Madhya Pradesh  Approved 
Ethical Review Board, Meenakshi Mission Hospital & Research Centre, Madurai, Tamil Nadu  Approved 
Ethical Review board, MS Ramaiah Medical College and Hospitals, Bangalore, Karnataka  Approved 
Ethics Committee, Belgaum Diabetes Centre  Approved 
Independent Ethics Committee, Kankarbagh, Patna, Bihar  Approved 
Institutional Ethics committee, BIBI General Hospital & Cancer Centre  Approved 
Institutional Ethics Committee, Deenanath Mangeshkar Hospital and Research Centre  Approved 
Institutional Ethics Committee, Vijayawada Andhra Pradesh  Approved 
Nagpur Independent Ethics Committee  Approved 
Research Independent Ethics Committee  Approved 
Sahyadri Hospitals Limited Ethic Committee, Pune, Maharashtra  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C719||Malignant neoplasm of brain, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  TEMODAL ® 250 mg capsules  One capsule of 250 mg of Temozolomide (Test or Reference) will be administered to the patients in each period. Theperiod I and period II will be the day 1 and day 2 of the treatment cycle.Temozolomide would be provided for the remaining doses of the cycle and remaining cycles to the patients as per PI’s discretion 
Intervention  Temozolomide capsule 250 mg  One capsule of 250 mg of Temozolomide (Test or Reference) will be administered to the patients in each period. The period I and period II will be the day 1 and day 2 of the treatment cycle. Temozolomide would be provided for the remaining doses of the cycle and remaining cycles to the patients as per PI’s discretion. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1.Signed written informed consent for participation in the trial. 2. Recovered from any toxic effects of previous chemotherapy as judged by the Investigator.3. Having a Body Mass Index (BMI) at least 17 calculated as weight in kg/height in m2. 4. Patients with a life expectancy of at least three months. 5. Patient with adequate bone marrow, renal and hepatic function. 6. Able to comply with study requirement in opinion of Principal Investigator 
 
ExclusionCriteria 
Details  1.Known hypersensitivity to Temozolomide, Dacarbazine or any other ingredients of the formulation
2.Use of any chemotherapy drugs within 21 days prior to dosing
3.History of drug/alcohol addiction
4.History of smoking or tobacco chewing in last 3 months
5.Known Galactose intolerant, known deficiency of the Lapp lactase or glucose-galactose malabsorption
6.A positive hepatitis screen including hepatitis B surface antigen, HCV or HAV (IgM) antibodies or positive VDRL test
7.Patients with HIV infection.
8.Positive for Drug of abuse test and alcohol screen test
9.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product for the current study.
 
 
Method of Generating Random Sequence   Permuted block randomization, fixed 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To characterize the pharmacokinetic profile of the sponsor’s test formulation (Temozolomide 250 mg capsules) relative to that of reference formulation
(TEMODAL® 250 mg capsules) in adult, male or female, patients under fasting conditions and to assess the bioequivalence
 
The venous blood samples will be withdrawn Pre-dose and 0.16 (10 min), 0.25
(15 min), 0.33 (20 min) 0.50 (30 min), 0.75 (45 min), 1.00, 1.25, 1.50, 2.00, 2.50,3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose in each period
administration. 
 
Secondary Outcome  
Outcome  TimePoints 
To monitor the safety of the patients exposed to the Investigational Medicinal Product  NIL 
 
Target Sample Size   Total Sample Size="40"
Sample Size from India="40" 
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" 
Phase of Trial   N/A 
Date of First Enrollment (India)
Modification(s)  
17/12/2012 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   NA 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

Temozolomide is an imidazotetrazine-alkylating agent with antitumor activity. At physiological pH the drug get metabolized to monomethyl triazeno imidazole carboxamide (MTIC). MTIC shows cytotoxicity due to alkylation at the O6 position of guanine with additional alkylation also occurring at the N7 position.

This study is being conducted to compare & characterize the relative bioavailability & pharmacokinetic profile of the Sponsor’s formulation (Temozolomide capsule 250 mg) with respect to the reference formulation (Temodal® (Temozolomide) capsules 250 mg) in single oral dose to adult patients with Glioblastoma Multiforme or Anaplastic Astrocytoma under fasting condition,who in the opinion of their treating physicians are candidates for the Temozolomide therapy.

Temozolomide is a cytotoxic drug; hence the study cannot be conducted on the healthy volunteer.

The primary objective of the study is to characterize the pharmacokinetic profile of the sponsor’s test formulation to that of reference formulation & secondary objective is to monitor the safety of the patients.

Bioequivalence will be concluded if the 90% confidence intervals for ln-transformed pharmacokinetic parameters Cmax and AUC0-t fall within the acceptance range of 0.8 – 1.25 for Temozolomide.

 
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