Bioequivalence of a Liquid Formulation of Alpha1-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha1-PI) in Alpha1-Antitrypsin Deficiency.

This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma-derived alpha(1)-proteinase inhibitor, Liquid Alpha(1)-PI, compared with the Lyophilized Alpha(1)-PI formulation (Prolastin (R)-C), for augmentation therapy in patients with alpha(1)-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(1)-PI or Lyophilized Alpha(1)-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(0-7days)) 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(0-7days) for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha(1)-PI concentration versus time curves for both formulations were superimposable. Mean AUC(0-7days) was 20 320 versus 19 838 mg x h/dl for Liquid Alpha(1)-PI and Lyophilized Alpha(1)-PI, respectively. The LS mean ratio of AUC(0-7days) (90% CI) for Liquid Alpha(1)-PI versus Lyophilized Alpha(1)-PI was 1.05 (1.03-1.08), indicating bioequivalence. Liquid Alpha(1)-PI was well tolerated and adverse events were consistent with Lyophilized Alpha(1)-PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha(1)-PI is bioequivalent to Lyophilized Alpha(1)-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.