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CTRI Number  CTRI/2013/04/003533 [Registered on: 04/04/2013] Trial Registered Prospectively
Last Modified On: 07/04/2014
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Bioequivalence study to compare Temodal and Temozolomide 250 mg capsules in patients with progressive or recurrent malignant glioma or advanced metastatic malignant melanoma under fasting condition. 
Scientific Title of Study   Multicenter open-label randomized crossover bioequivalence study of BCD-029 (CJSC Biocad, Russia) and Temodal® (Schering-Plough Labo N.V.) in capsules after single oral administration (under fasting conditions) in patients with progressive or recurrent malignant glioma or advanced metastatic malignant melanoma. 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
Protocol No. BCD-029-1 Version No. 1.0 dated 31st July 2012  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Jayaveena MN 
Designation  Project Manager 
Affiliation  Biocad India Private Limited  
Address  163/C, 3rd Cross, 3rd Phase, JP Nagar

Bangalore
KARNATAKA
560078
India 
Phone  9591074318  
Fax  08041699773  
Email  Jayaveena.MN@biocadindia.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Jayaveena MN 
Designation  Project Manager 
Affiliation  Biocad India Private Limited  
Address  163/C, 3rd Cross, 3rd Phase, JP Nagar

Bangalore
KARNATAKA
560078
India 
Phone  9591074318  
Fax  08041699773  
Email  Jayaveena.MN@biocadindia.com  
 
Details of Contact Person
Public Query  
Name  Kavita Mahendra 
Designation  Sr. Manager Regulatory Affairs 
Affiliation  Biocad India Private Limited  
Address  163/C, 3rd Cross, 3rd Phase, JP Nagar

Bangalore
KARNATAKA
560078
India 
Phone  9591074318  
Fax  08041699773  
Email  Kavita.Mahendra@biocadindia.com  
 
Source of Monetary or Material Support  
Closed joint stock company BIOCAD (CJSC BIOCAD), Russia. Address: Svyazi st. 34 А, Strelna, Petrodvortsovy District, Saint Petersburg, 198515 Russia 
 
Primary Sponsor  
Name  Biocad India Private Limited 
Address  163/C, 3rd Cross, 3rd Phase, JP Nagar, Bengaluru 5660078, Karnataka 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 4  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr V Satya Suresh Attili  Bibi General Hospital and Cancer Center  3rd Floor, Room No 308, Clinical Research Division, 16-3-991/1/C, Government Printing Press Road, Malakpet, Hyderabad – 500024,Andhra Pradesh, India
Hyderabad
ANDHRA PRADESH 		 09246243034
04024528144
sureshattili@yahoo.com 
Dr LK Rajeev  Chinmaya Mission Hospital  2nd floor, Oncology department, Room No. S8, 80 feet road, Indiranagar, Bangalore – 560038
Bangalore
KARNATAKA 		 9886585797
08025205005
lk_rajeev@yahoo.co.in 
Dr SS Nirni  Omega Hospitals  2nd floor sharing side, Clinical Research room, MLA Colony Main road, Road No. 12, Banjara Hills Hyderabad- 500 034
Hyderabad
ANDHRA PRADESH 		 09849062003
04023550327
nirni2002@rediffmail.com 
Dr Chiradoni Tungappa Satheesh  Sri Venkateshwara Hospital  3rd Floor, Clinical Research department, # 86, Hosur Main Road, Madiwala, Bangalore – 560068
Bangalore
KARNATAKA 		 9242698750
08025630006
drsatheeshct@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 4  
Name of Committee  Approval Status 
Bangalore Ethics, Bangalore, PI- Dr. CT Satheesh  Approved 
Bangalore Ethics, Bangalore, PI- Dr. LK Rajeev   Approved 
BiBi General Hospital and Cancer Center Ethics Committee, Hyderabad, PI-Dr. V Satya Suresh Attili  Approved 
Daksh Independent Ethics Committee, Hyderabad, PI-Dr. S S Nirni   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Progressive or recurrent malignant glioma or advanced metastatic malignant melanoma. ,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Temodal (Temozolomide) capsule 250 mg   In chemotherapy-naïve patients with progressive or relapsed malignant glioma in the form of glioblastoma multiforme or anaplastic astrocytoma (adults and children more than 3 years old) and advanced metastatic malignant melanoma (adults), the drug is administered in the dose of 200 mg/m2 once daily for 5 days followed by 23 days without treatment (a treatment cycle comprises 28 days). In patients previously treated with chemotherapy, the initial dose is 150 mg/m2 once daily; in the second cycle the dose might be increased to 200 mg/m2 once daily provided that absolute neutrophil count is ≥ 1.5 x 109/L and platelet count is ≥ 100 Ñ… 109/L at the first day of the next cycle. Within this study the drug will be administered orally at fasting condition - on Day 1/Day 2 at the dose of 250 mg and then from Day 3 to Day 5 in such a dose that the total dose for the 5-days cycle will be 1,000 mg/m2.  
Intervention  Temozolomide (CJSC Biocad) Capsules 250 mg   In chemotherapy-naïve patients with progressive or relapsed malignant glioma in the form of glioblastoma multiforme or anaplastic astrocytoma (adults and children more than 3 years old) and advanced metastatic malignant melanoma (adults), the drug is administered in the dose of 200 mg/m2 once daily for 5 days followed by 23 days without treatment (a treatment cycle comprises 28 days). In patients previously treated with chemotherapy, the initial dose is 150 mg/m2 once daily; in the second cycle the dose might be increased to 200 mg/m2 once daily provided that absolute neutrophil count is ≥ 1.5 x 109/L and platelet count is ≥ 100 Ñ… 109/L at the first day of the next cycle. Within this study, the drug product will be administered orally on Day 1/Day 2 in the dose of 250 mg at fasting condition.  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. An informed consent signed
2. Documented progressive or recurrent malignant glioma (glioblastoma multiforme or anaplastic astrocytoma) with a relapse or progression after standard therapy or advanced metastatic malignant melanoma
3. The period from the date of the last chemotherapeutic drug administration (if applicable) to the date of the first planned study drug (Temozolomide) administration within the clinical study is no less than 23 days.
4. 18 to 65 years of age (both inclusive)
5. ECOG 0 to 2
6. Life expectancy is greater than or equal to 12 weeks from the date of the study enrollment
7. Negative test results for hepatitis B, C, HIV and syphilis dated no more than 6 weeks before the screening examination.
8.Pre specified laboratory values hemoglobin greater than or equal to 100 g per L, ANC greater than or equal to 1.5 Ñ… 109 per L, platelet count greater than or equal to 100 Ñ… 109 per L, hepatic enzymes level (AST, ALT, ALP, GGT) less than or equal to 2.5 x ULN (less than or equal to 5 x ULN is acceptable if liver metastases are present), total plasma bilirubin and plasma creatinine are greater than or equal to ULN.
9. Body Mass Index (BMI) is within normal range (18.5 to 24.99 kg per m2).
10. Hemodynamic parameters are within normal range: SBP is within 100 to 130 mm Hg, DBP is within 60 to 90 mm Hg, Heart Rate is within 50 to 90 bpm.
11. The ability of a patient to comply with the requirements of the protocol according to the Investigator’s opinion.
12. Male and female patients with normal reproductive function and their sexual partners are aware and willing to use voluntarily reliable methods of contraception from 4 weeks before the enrollment to the study and up to 6 months after the administration of the last dose of the study drug products. This requirement does not apply to patients who underwent operative sterilization or those defined as post-menopausal (documentally confirmed) within last 2 years. Reliable methods of contraception suggest using 1 barrier method in combination with 1 of the following methods spermicides intra-uterine device.
13. Willingness not to drink alcohol within 24 hours prior to the first dosing of Test drug or reference drug and within 48 hours after the last dosing.
14. Willingness not to drink grapefruit juice or grapefruit-containing foods within 72 hours prior to the first dosing of Test drug or reference drug and within 72 hours after the last dosing.
 
 
ExclusionCriteria 
Details  1. Aggravated allergological anamnesis (e.g., history of multi-drug allergy, anaphylactic shock etc.)
2. Known hypersensitivity or idiosyncratic reaction to Temozolomide or any other ingredients of the Test drug or the reference drug, as well as to dacarbazine.
3. Confirmed lactose intolerance or other rare hereditary diseases such as saccharose and fructose intolerance, lactase and sucrase- isomaltase deficiency or glucose-galactose malabsorption.
4. Psychiatric disorders and other conditions that might interfere with the ability of a patient to follow the study protocol.
5. History of gastrointestinal surgery (with the exception of appendectomy performed no less than 30 days prior to the screening examination).
6. Any acute or chronic infection at the time of screening examination; acute infection of bacterial, virus, or mycotic origin less than 4 weeks prior to the study initiation.
7. Inability to insert the venous catheter for blood sampling (e.g., due to a skin disease at the venipuncture sites);
8. Any diseases or other conditions that might influence the pharmacokinetics of the Test drug/the reference drug, for example:

- intestinal malabsorption;
- severe hepatic or renal dysfunction (hepatic enzymes level (AST, ALT, ALP, GGT) greater than 2.5 x ULN (greater than 5 x ULN if liver metastases are present), total blood bilirubin and plasma creatinine greater than ULN;
- cardiovascular disorders (severe refractory idiopathic hypertension, decompensated cardiac disorders (III-IV class CHF according to NYHA);
- decompensated respiratory insufficiency, tumor infiltration of lungs;
- neuroendocrine disorders (e.g., severe refractory diabetes mellitus);
- autoimmune disorders;
- epileptic seizures.
9. A history of any other neoplasm with the exception of adequately treated basal-cell carcinoma or cervical carcinoma in situ and cases with the remission period of no less than 5 years.
10. The use of medicines (including non-prescription) and dietary supplements, which have pronounced influence on hemodynamics, liver function etc. (barbiturates, omeprazole, cimetidine etc.), less than 30 days prior to the study initiation. Conditions requiring the constant use of systemic corticosteroids. Received blood less than 2 weeks prior to the beginning of the screening examination.
11. Pregnancy and lactation.
12. Smoking more than 10 cigarettes per day.
13. Consumption of more than 10 units of alcohol per week (1 unit is equivalent to 0.5 L of beer, 200 mL of wine or 50 mL of pure alcohol) or a history of alcoholism, narcomania or drug abusing.
14. Donation of greater than or equal to 450 mL of blood or plasma within 3 months prior to the study enrollment.
15. Participation in any clinical trials less than 3 months prior to the study enrollment.
16. Simultaneous participation in other clinical trials.
17. Previous participation in this study.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Assessment of pharmacokinetic parameters after single administration of the Test drug and the reference drug: Temozolomide maximum plasma concentration , time to maximum plasma concentration , area under concentration-time curve (AUC) from the moment of the drug product administration to Тmax, 12 h and to infinity (AUC(0-tmax), AUC(0-12), AUC(0-∞), respectively) within 12 hours after single oral administration of the Test drug or the reference drug.  10 min, 20 min, 30 min, 45 min, 1hr, 1hr 20 min, 1hr 40 min, 2 hrs, 2 hrs 30 min, 3hrs, 4hrs, 6hrs, 8hrs, and 12 hours after the test or reference administration 
 
Secondary Outcome  
Outcome  TimePoints 
Assessment of Safety parameters after one dose of one of the investigational drugs during the study
• AEs and SAEs incidence;
• Grade 3-4 CTCAE 4.0 AEs incidence;
• Incidence of treatment discontinuation due to AEs.
 		 AEs: recorded from the beginning of the therapy until day 28 after the patient’s withdrawal or study termination.
SAEs: recorded from the moment of signing informed consent form till end of study
 
 
Target Sample Size   Total Sample Size="18"
Sample Size from India="18" 
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" 
Phase of Trial   N/A 
Date of First Enrollment (India)   17/04/2013 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  17/04/2013 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Completed 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  

This is an open-label comparative randomized crossover bioequivalence study. Upto 18 patients with progressive or recurrent MG (GBM or AA) and advanced mMM will be recruited into the study. The study will be conducted at 4 sites in India. Primary goal of the study is to study the bioequivalence of BCD-029 (CJSC Biocad, Russia) 250 mg capsule and Temodal® (Schering-Plough Labo N.V., Belgium) 250 mg capsule after single oral administration, under fasting conditions in patients with progressive or recurrent malignant glioma (MG), glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) and advanced metastatic malignant melanoma (mMM). Secondary goal of the study is to compare safety results obtained for BCD-029 (CJSC Biocad, Russia) 250 mg capsule with those obtained for Temodal® (Schering-Plough Labo N.V., Belgium) 250 mg capsule after single oral administration , under fasting conditions in patients with progressive or recurrent MG (GBM or AA) and advanced mMM.

 
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