CTRI/2012/03/002482 [Registered on: 06/03/2012] Trial Registered Prospectively
Last Modified On:
24/11/2018
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A multicentre, randomized, A cmparision between two Gemcitabine formulation to prove ithe equivalence in patients with Pancreatic or Ovarian Cancer
Scientific Title of Study
A multicentre, randomized, open label, two-period, two-treatment, two-way crossover, single dose bioequivalence study comparing Gemcitabine injection (Manufactured by: Intas Pharmaceuticals Ltd.) to the reference listed drug Gemzar injection (Eli Lilly and Company, Indianapolis, IN 46285, USA) in patients with Pancreatic or Ovarian Cancer
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
655-10, version 02
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Kshitij Soni
Designation
AGM
Affiliation
Lambda Therapeutic Research
Address
Lambda Therapeutic Research Ltd.,
Near Gujarat High courat,
S. G. Highway, Gota,
Ahmedabad -Gujarat, India
- Ahmadabad GUJARAT 380 061 India
Phone
079-40202322
Fax
Email
kshitijsoni@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Praveen Shetty
Designation
Medical lead
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd.,
Near Gujarat High courat,
S. G. Highway, Gota,
Ahmedabad -Gujarat, India
- Ahmadabad GUJARAT 380 061 India
Phone
079-40202098
Fax
Email
praveenshetty@lambda-cro.com
Details of Contact Person Public Query
Name
Dr Praveen Shetty
Designation
Medical lead
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd.,
Near Gujarat High courat,
S. G. Highway, Gota,
Ahmedabad -Gujarat, India
-
GUJARAT 380 061 India
Phone
079-40202098
Fax
Email
praveenshetty@lambda-cro.com
Source of Monetary or Material Support
Intas Pharmaceuticals Ltd
Primary Sponsor
Name
Intas Pharmaceuticals Ltd
Address
Intas Pharmaceuticals Ltd, 2nd Floor, Chinubhai Center, Ashram Road, Ahmedabad 380-009, Gujarat, India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 8
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Tanveer Maksud
Bharat Cancer Hospital & Research Institute,
Room No. 22/C, OPD department,Manav Daya Trust Complex, Surat Bardoli, Saroli, Surat – 39501 Surat GUJARAT
(1) ICD-10 Condition: C259||Malignant neoplasm of pancreas, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Gemcitabine Injection Concentrate
2gm/20 ml
Intas Pharmaceuticals Ltd.
2nd Floor, Chinubhai Centre,
Ashram Road,
Ahmedabad-380009, Gujarat, India
As per the Prescribing Information of the reference product, the dosing schedule for the ovarian and pancreatic cancers is as follows:
For Ovarian Cancer patients:
Gemcitabine should be administered intravenously at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. Carboplatin should be administered intravenously on Day 1 anytime after Gemcitabine administration. Up to 06 such treatment cycles may be administered.
For Pancreatic Cancer patients:
Gemcitabine should be administered intravenously at a dose of 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitates reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3 consecutive weeks out of every 4 weeks.
Dosing schedule for the study:
Taking the above schedule in to consideration, the dosing schedule for this study would be as follows:
For Ovarian Cancer patients:
Note: Any one of the 06 treatment cycles given for ovarian cancer can be chosen for the study. However, once chosen, the period 01 (day 01 of the cycle) and period 02 (day 08 of the cycle) should be completed in that cycle itself.
Period 01:
Patients will be dosed Gemcitabine Injection (either test or reference product as per randomization schedule) at a dose of 1000 mg/m2 over 30 minutes (+ 5 minutes deviation is allowed) on Day 01 of the 21 day cycle.
Period 02:
Patients will be dosed Gemcitabine Injection (either test or reference product as per randomization schedule) at a dose of 1000 mg/m2 over 30 minutes (+ 5 minutes deviation is allowed) on Day 08 of the 21 day cycle.
For Pancreatic Cancer patients:
Note: Any two consecutive weeks out of the 07 week cycle or the subsequent cycles can be chosen for conducting the period I and II of the study. However, the dosing days have to be separated by at least 07 days each. For e.g. the week 02 and week 03 of the 07 week cycle may be chosen for the study. In this case, the dosing day of week 02 will be the period 01 of the study and the dosing day of week 03 will be the period II of the study.
Period I:
Patients will be dosed Gemcitabine Injection (either test or reference product as per randomization schedule) at a dose of 1000 mg/m2 over 30 minutes (+ 5 minutes deviation is allowed) on the day 01 of the week on which the patient is supposed to receive his/her weekly dose.
Period II:
Patients will be dosed Gemcitabine Injection (either test or reference product as per randomization schedule)at a dose of 1000 mg/m2 over 30 minutes (+ 5 minutes deviation is allowed) on the day 01 of the subsequent dosing week (there has to be a gap of 07 days between period I and period II).
Preferably the time of administration of dose in period 01 will be the reference time for period 02 dosing. A deviation of +1 day will be allowed over and above the stipulated 7 day break between the 2 dosings.
Comparator Agent
Reference Product-B
Gemzar® Injection powder, lyophilized
1 gm/vial
Eli Lilly and Company
Indianapolis, IN 46285, USA
As per the Prescribing Information of the reference product, the dosing schedule for the ovarian and pancreatic cancers is as follows: For Ovarian Cancer patients: Gemcitabine should be administered intravenously at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. Carboplatin should be administered intravenously on Day 1 anytime after Gemcitabine administration. Up to 06 such treatment cycles may be administered. For Pancreatic Cancer patients: Gemcitabine should be administered intravenously at a dose of 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitates reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3 consecutive weeks out of every 4 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Able to give written informed consent for participation in the trial.
2. Male and female patients between the ages of 18 and 65 years.
3. Patients with Histo-pathologically or through Fine Needle Aspiration Cytology (FNAC) confirmed
 Locally Advanced (non-resectable Stage II or Stage III) or Metastatic (Stage IV) Adenocarcinoma of the Pancreas (Gemcitabine as first line treatment)
‘OR’
 Pancreatic cancer patients previously treated with 5-Fluorouracil
‘OR’
 Advanced Ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy (Gemcitabine in combination with Carboplatin)
4. Recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
5. Patients if already on Radiotherapy, a gap of at least one week shall be maintained between the last day of radiotherapy and the day of screening
6. Patients with life expectancy of at least 2 months
7. Able to comply with study requirement in opinion of Principal Investigator.
8. Adequate hepatic, renal and hematopoietic function.
ExclusionCriteria
Details
1. Known hypersensitivity reaction to Gemcitabine and any ingredient of the formulation.
2. Use of any recreational drugs or history of drug addiction.
3. History of psychiatric disorders.
4. A positive hepatitis screen including hepatitis B surface antigen, HCV and HAV antibodies.
5. Known case of HIV infection.
6. Pregnant or breast-feeding women.
7. The receipt of an investigational drug or product, or participation in a drug research study within a period of 60 days prior to the first dose of investigational Product (Elimination half-life of the study drug should be taken into consideration for inclusion of the patient in the study).
Method of Generating Random Sequence
Other
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To characterize the pharmacokinetic profile of the sponsor’s test formulation relative to that of reference formulation in patients and to assess the bioequivalence
Day 7 of the patients PK analysis
Secondary Outcome
Outcome
TimePoints
To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product.
up to 30 days afgter last study drug administration
Target Sample Size
Total Sample Size="66" Sample Size from India="66" 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
This is a multicentre, randomized, open label, two-period, two-treatment, two-way crossover, single dose bioequivalence study comparing Gemcitabine injection (Manufactured by:Intas Pharmaceuticals Ltd.) to the reference listed drug Gemzar injection (Eli Lilly and Company, Indianapolis, IN 46285, USA) in patients with Pancreatic or Ovarian Cancer
Gemcitabine exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and also blocking the progression of cells through the G1/S-phase boundary. Gemcitabine is metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. The cytotoxic effect of gemcitabine is attributed to a combination of two actions of the diphosphate and the triphosphate nucleosides, which leads to inhibition of DNA synthesis. First, gemcitabine diphosphate inhibits ribonucleotide reductase, which is responsible for catalyzing the reactions that generate the deoxynucleoside triphosphates for DNA synthesis. Inhibition of this enzyme by the diphosphate nucleoside causes a reduction in the concentrations of deoxynucleotides, including dCTP. Second, gemcitabine triphosphate competes with dCTP for incorporation into DNA. The reduction in the intracellular concentration of dCTP (by the action of the diphosphate) enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation). After the gemcitabine nucleotide is incorporated into DNA, only one additional nucleotide is added tothe growing DNA strands.
Primary Objective:
To characterize the pharmacokinetic profile of the sponsor’s test formulation relative to that of reference formulation in patients and to assess the bioequivalence.
Secondary Objective:
To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product.
1.1Method of Administration
·The dose of Gemcitabine HCl for individual patient will be calculated according to body surface area. (Calculated by Dubois formula). The BSA measured on day 0 should be used to calculate the dose for the entire duration of the study.
·Reference Product: The recommended diluent for reconstitution of Gemzar is 0.9% Sodium Chloride Injection without preservatives. Due to solubility considerations, the maximum concentration for Gemzar upon reconstitution is 40 mg/mL. Reconstitution at concentrations greater than 40 mg/mL may result in incomplete dissolution, and should be avoided. To reconstitute, add 25 mL of 0.9% Sodium Chloride Injection to the 1-g vial. Shake to dissolve. This dilution yields a Gemcitabine concentration of 38 mg/mL which includes accounting for the displacement volume of the lyophilized powder (1.3 mL for the 1-g vial). The total volume upon reconstitution will be 26.3 mL. Complete withdrawal of the vial contents will provide 1 g of Gemcitabine. The appropriate amount of drug may be administered as prepared or further diluted with 0.9% Sodium Chloride Injection to concentrations as low as 0.1 mg/mL. However, since this is a PK study therefore the concentration of Gemzar would be fixed at 5 mg/mL. Reconstituted Gemzar is a clear, colorless to light straw-colored solution. After reconstitution with 0.9% Sodium Chloride Injection, the pH of the resulting solution lies in the range of 2.7 to 3.3. The solution should be inspected visually for particulate matter and discoloration prior to administration, whenever solution or container permits. If particulate matter or discoloration is found, do not administer. When prepared as directed, Gemzar solutions are stable for 24 hours at controlled room temperature 20° to 25°C (68° to 77°F). Discard unused portion. Solutions of reconstituted Gemzar should not be refrigerated, ascrystallization may occur.
·Test Product: The recommended diluent for reconstitution of the Test Product is 0.9% Sodium Chloride Injection. The appropriate amount of drug to be administered after further dilution with 0.9% Sodium Chloride Injection to concentrations as low as 0.1 mg/mL. However, since this is a PK study therefore the concentration of the Test Product would be fixed at 5 mg/mL. Reconstituted Gemcitabine is a clear, colorless to light straw-colored solution. After reconstitution with 0.9% Sodium Chloride Injection, the pH of the resulting solution lies in the range of 6.0-7.0.