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

Alan F. Barker, Michael A Campos, Mark L. Brantly, James M. Stocks, Robert A. Sandhaus, Douglas Lee, Kimberly Steinmann, Jiang Lin, Susan Sorrells

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma–derived alpha1-proteinase inhibitor, Liquid Alpha1-PI, compared with the Lyophilized Alpha1-PI formulation (Prolastin®-C), for augmentation therapy in patients with alpha1-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 Alpha1-PI or Lyophilized Alpha1-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 (AUC0–7 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 AUC0–7 days for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha1-PI concentration versus time curves for both formulations were superimposable. Mean AUC0–7 days was 20 320 versus 19 838 mg × h/dl for Liquid Alpha1-PI and Lyophilized Alpha1-PI, respectively. The LS mean ratio of AUC0–7 days (90% CI) for Liquid Alpha1-PI versus Lyophilized Alpha1-PI was 1.05 (1.03–1.08), indicating bioequivalence. Liquid Alpha1-PI was well tolerated and adverse events were consistent with Lyophilized Alpha1-PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha1-PI is bioequivalent to Lyophilized Alpha1-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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalCOPD: Journal of Chronic Obstructive Pulmonary Disease
DOIs
StateAccepted/In press - Oct 5 2017

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alpha 1-Antitrypsin
Therapeutic Equivalency
Peptide Hydrolases
Least-Squares Analysis
Safety
Confidence Intervals
Cross-Over Studies
Therapeutics

Keywords

  • Antigenic content assay
  • augmentation therapy
  • clinical trial
  • functional activity assay
  • pharmacokinetics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Bioequivalence of a Liquid Formulation of Alpha1-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha1-PI) in Alpha1-Antitrypsin Deficiency. / Barker, Alan F.; Campos, Michael A; Brantly, Mark L.; Stocks, James M.; Sandhaus, Robert A.; Lee, Douglas; Steinmann, Kimberly; Lin, Jiang; Sorrells, Susan.

In: COPD: Journal of Chronic Obstructive Pulmonary Disease, 05.10.2017, p. 1-7.

Research output: Contribution to journalArticle

Barker, Alan F. ; Campos, Michael A ; Brantly, Mark L. ; Stocks, James M. ; Sandhaus, Robert A. ; Lee, Douglas ; Steinmann, Kimberly ; Lin, Jiang ; Sorrells, Susan. / Bioequivalence of a Liquid Formulation of Alpha1-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha1-PI) in Alpha1-Antitrypsin Deficiency. In: COPD: Journal of Chronic Obstructive Pulmonary Disease. 2017 ; pp. 1-7.
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abstract = "This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma–derived alpha1-proteinase inhibitor, Liquid Alpha1-PI, compared with the Lyophilized Alpha1-PI formulation (Prolastin{\circledR}-C), for augmentation therapy in patients with alpha1-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 Alpha1-PI or Lyophilized Alpha1-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 (AUC0–7 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 AUC0–7 days for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha1-PI concentration versus time curves for both formulations were superimposable. Mean AUC0–7 days was 20 320 versus 19 838 mg × h/dl for Liquid Alpha1-PI and Lyophilized Alpha1-PI, respectively. The LS mean ratio of AUC0–7 days (90{\%} CI) for Liquid Alpha1-PI versus Lyophilized Alpha1-PI was 1.05 (1.03–1.08), indicating bioequivalence. Liquid Alpha1-PI was well tolerated and adverse events were consistent with Lyophilized Alpha1-PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha1-PI is bioequivalent to Lyophilized Alpha1-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.",
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AU - Brantly, Mark L.

AU - Stocks, James M.

AU - Sandhaus, Robert A.

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AU - Lin, Jiang

AU - Sorrells, Susan

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