Inderjeet Singh1, Akash Patel2, Ronak Patel2, Vinu Jose3. 1. Intas Pharmaceuticals Ltd. (Biopharma), Plot No: 423/P/A, Sarkhej-Bavla Highway, Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India. 2. Lambda Therapeutic Research Ltd., Lambda House, Plot No. 38, Survey No. 388, Near Silver Oak Club, S. G. Highway, Gota, Ahmedabad, Gujarat, 382481, India. 3. Intas Pharmaceuticals Ltd. (Biopharma), Plot No: 423/P/A, Sarkhej-Bavla Highway, Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India. vinu_jose@intaspharma.com.
Abstract
PURPOSE: This study compared pharmacokinetics, pharmacodynamics, safety and immunogenicity profiles of INTP5 (a potential pegfilgrastim biosimilar) with that of Neulasta®. METHODS: In this randomised, assessor-blind, crossover study, 344 healthy subjects receivedsingle subcutaneous dose of both INTP5 and Neulasta at 3 mg/0.3 ml (n = 172) or 6 mg/0.6 ml (n = 172) dose. The primary endpoints were AUC0-t, AUC0-∞ and Cmax of pegfilgrastim; and AUEC0-t and Emax of absolute neutrophil count (ANC). RESULTS:All 344 subjects dosed were included in the safety and immunogenicity analyses, and 292 subjects in the pharmacokinetic and pharmacodynamic analyses. At 6 mg dose, test to reference ratio (90% CI) of AUC0-t was 105.65% (99.60-112.06%), AUC0-∞ was 105.72% (99.55-112.28%) and Cmax was 103.62% (98.19-109.35%); while test to reference ratio (95% CIs) of ANC AUEC0-t was 100.79% (97.75-103.92%) and Emax was 98.70% (95.52-101.98%). Both the primary endpoints met the bioequivalence criteria (CIs within 80-125%). Similarly, at 3 mg dose, these endpoints were within the acceptance range of 80-125%. CD34+ profiles were similar and 95% CIs were within acceptance range at both doses. Adverse events were reported in 54 (15.7%; 8.72% in INTP5 vs. 8.39% in Neulasta) subjects; most events were mild. The incidences of anti-drug antibodies were low and similar between INTP5 and Neulasta and no neutralising antibodies were detected. CONCLUSIONS:Pharmacokinetic and pharmacodynamic bioequivalence was established between INTP5 and Neulasta following 3 and 6 mg doses. Safety and immunogenicity profiles were similar between INTP5 and Neulasta.
RCT Entities:
PURPOSE: This study compared pharmacokinetics, pharmacodynamics, safety and immunogenicity profiles of INTP5 (a potential pegfilgrastim biosimilar) with that of Neulasta®. METHODS: In this randomised, assessor-blind, crossover study, 344 healthy subjects received single subcutaneous dose of both INTP5 and Neulasta at 3 mg/0.3 ml (n = 172) or 6 mg/0.6 ml (n = 172) dose. The primary endpoints were AUC0-t, AUC0-∞ and Cmax of pegfilgrastim; and AUEC0-t and Emax of absolute neutrophil count (ANC). RESULTS: All 344 subjects dosed were included in the safety and immunogenicity analyses, and 292 subjects in the pharmacokinetic and pharmacodynamic analyses. At 6 mg dose, test to reference ratio (90% CI) of AUC0-t was 105.65% (99.60-112.06%), AUC0-∞ was 105.72% (99.55-112.28%) and Cmax was 103.62% (98.19-109.35%); while test to reference ratio (95% CIs) of ANC AUEC0-t was 100.79% (97.75-103.92%) and Emax was 98.70% (95.52-101.98%). Both the primary endpoints met the bioequivalence criteria (CIs within 80-125%). Similarly, at 3 mg dose, these endpoints were within the acceptance range of 80-125%. CD34+ profiles were similar and 95% CIs were within acceptance range at both doses. Adverse events were reported in 54 (15.7%; 8.72% in INTP5 vs. 8.39% in Neulasta) subjects; most events were mild. The incidences of anti-drug antibodies were low and similar between INTP5 and Neulasta and no neutralising antibodies were detected. CONCLUSIONS: Pharmacokinetic and pharmacodynamic bioequivalence was established between INTP5 and Neulasta following 3 and 6 mg doses. Safety and immunogenicity profiles were similar between INTP5 and Neulasta.