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

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 to  the growing DNA strands.

Primary Objective: xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

 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.

1.1        Method of Administration

 Â·         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, as  crystallization 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.