Bioequivalence of a Liquid Formulation of Alpha 1 -Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha 1 -PI) in Alpha 1 -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®-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 _0-7 days ) 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 _0-7 days 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 _0-7 days was 20 320 versus 19 838 mg × h/dl for Liquid Alpha ₁ -PI and Lyophilized Alpha ₁ -PI, respectively. The LS mean ratio of AUC _0-7 days (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.