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Brief Summary
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This is a multicenter, open label, randomized, single dose, two-treatment, two-period, two-sequence, crossover, bioequivalence study with pharmacokinetic endpoint. There will be a screening period up to 14 days. If the patient passes all the screening criteria, PI can immediately enroll the patient and can consider that day as Day -1. This will be a two-period study. Period 1 dosing will be on Day 1 and Period 2 dosing will be on Day 22. There will be 11 patient visits to the study site; Visit 1-Screening (Day -14 to -1), Visit 2-Day -1, Visit 3- Day 5, Visit 4-Day 6, Visit 5- Day 7, Visit 6-Day 14, Visit 7- Day 21, Visit 8-Day 26, Visit 9- Day 27, Visit 10- Day 28 and Visit 11- Day 35 plus 2. Total duration of the study will be approximately 51 days. All eligible patients will be advised to visit the study site on Day -1 for randomization and will be confined till Day 4 for Period 1. Patients will be requested to visit on Day 5, Day 6, and Day 7 for ambulatory sample collection. Patients will be requested to visit the study site on Day 14 for ANC sample collection and then on Day 21 for Period 2 followed by confinement till Day 25. Patients will be requested to visit on Day 26, Day 27, and Day 28 for ambulatory sample collection. Patients may be confined till last sample of collection in respective period as per investigator’s discretion considering patient condition. Patients will be administered with any antiemetic medication within 1 hour prior to dosing on Day 1 and Day 22 to prevent nausea and vomiting. To minimize the risk of severity of hypersensitivity reactions, patients will receive Dexamethasone 20 mg intravenously within 45 minutes prior to the dose on Day 1 and Day 22 as per the institution or investigator’s discretion. Pre-medications can be administered as per the institution or investigator’s discretion, and it should be same in both periods of the study. After fasting of at least 10 hours, patients will be dosed with Paclitaxel suspension for injection (either Test or Reference product as per randomization schedule) as an intravenous infusion at a dose 260 mg per m2 over 30 minutes plus 5 minutes in each period i.e., on Day 1 (Period 1) and Day 22 (Period 2) by Study Nurse and or or Investigator. If the patient’s health status prevents fasting, then a non-high-fat diet will be provided for both study periods under same conditions during the study. If the patient’s health status necessitates a dose reduction or any change in the recommended 260 mg per m2 dose administered in 30 minutes, such patient’s will be withdrawn from the study. On Day 1 and Day 22, complete PK sampling will be performed. Venous blood samples (approximately 3 mL) will be withdrawn at 0.00 (prior to infusion), and 0.08, 0.17, 0.25, 0.33, 0.42 (during infusion), 0.50 (i.e., immediately at the end of the infusion [a window period of plus 2 minutes will be allowed]), 0.67, 0.75, 1.00, 1.25, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00, 96.00, 120.00 and 144.00 hours after the start of the infusion (24 samples, 72 mL of blood and 9.5 mL heparinized blood in each period). Pre dose sample will be obtained within 30 minutes before dosing, sample collection during infusion and post end of infusion, a window period of plus minus 2 minutes is allowed during inhouse sample collection and plus minus 2 hours for ambulatory sample collection. The blood will be collected in Na Heparin vacutainers tubes. Blood loss for safety assessments at Screening, Randomization and End of Study Visits will be 45 mL (15 mL each), 144 mL for PK samples, 3 mL for ANC (Absolute neutrophil count) testing on Day 14, 19 mL heparinized blood, and 6 mL (3 mL each) for Hematology and LFT on Day 21. Total blood loss during the study will be 217 mL. Patients will be requested to visit the site on Day 35 plus 2 days for end of study evaluation. Study medication administration, blood sample collection, processing and analysis should be done under yellow monochromatic light. |