Bioequivalence of a Liquid Formulation of Alpha-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha-PI) in Alpha-Antitrypsin Deficiency.

This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma-derived alpha-proteinase inhibitor, Liquid Alpha-PI, compared with the Lyophilized Alpha-PI formulation (Prolastin®-C), for augmentation therapy in patients with alpha-antitrypsin deficiency (AATD). In this double-blind, randomized, 20-week crossover study, 32 subjects with AATD were randomized to receive 8 weekly infusions of 60 mg/kg of Liquid Alpha-PI or Lyophilized Alpha-PI. Serial blood samples were drawn for 7 days after the last dose followed by 8 weeks of the alternative treatment. The primary endpoint was bioequivalence at steady state, as measured by area under the concentration versus time curve from 0 to 7 days (AUC) postdose using an antigenic content assay. Bioequivalence was defined as 90% confidence interval (CI) for the ratio of the geometric least squares (LS) mean of AUC for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha-PI concentration versus time curves for both formulations were superimposable. Mean AUC was 20 320 versus 19 838 mg × h/dl for Liquid Alpha-PI and Lyophilized Alpha-PI, respectively. The LS mean ratio of AUC (90% CI) for Liquid Alpha-PI versus Lyophilized Alpha-PI was 1.05 (1.03-1.08), indicating bioequivalence. Liquid Alpha-PI was well tolerated and adverse events were consistent with Lyophilized Alpha-PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha-PI is bioequivalent to Lyophilized Alpha-PI, with a similar safety profile. The liquid formulation would eliminate the need for reconstitution and shorten preparation time for patients receiving augmentation therapy for AATD.