Pharmacokinetic comparability of Prolastin？-C to Prolastin？ in alpha1-antitrypsin deficiency: a randomized study

In total, 24 subjects were randomized to receive 60 mg/kg of functionally active Prolastin-C or Prolastin by weekly intravenous infusion for 8 weeks before crossover to the alternate treatment for another 8 weeks. Pharmacokinetic plasma samples were drawn over 7 days following last dose in the first treatment period and over 10 days following the last dose in the second period. The primary end point for pharmacokinetic comparability was area under the plasma concentration versus time curve over 7 days post dose (AUC0-7 days) of alpha1-PI determined by potency (functional activity) assay. The crossover phase was followed by an 8-week open-label treatment phase with Prolastin-C only.Mean AUC0-7 days was 155.9 versus 152.4 mg*h/mL for Prolastin-C and Prolastin, respectively. The geometric least squares mean ratio of AUC0-7 days for Prolastin-C versus Prolastin had a point estimate of 1.03 and a 90% confidence interval of 0.97-1.09, demonstrating pharmacokinetic equivalence between the 2 products. Adverse events were similar for both treatments and occurred at a rate of 0.117 and 0.078 per infusion for Prolastin-C (double-blind treatment phase only) and Prolastin, respectively (p = 0.744). There were no treatment-emergent viral infections in any subject for human immunodeficiency virus, hepatitis B or C, or parvovirus B19 during the course of the study.Prolastin-C demonstrated pharmacokinetic equivalence and a comparable safety profile to Prolastin.ClinicalTrials.gov Identifier: NCT00295061Alpha1-antitrypsin (AAT) deficiency is an inherited autosomal disorder characterized by low blood levels of alpha1-proteinase inhibitor (alpha1-PI) and is one of the most common yet under recognized single-locus genetic diseases [1]. The disorder may lead to progressive severe emphysema that can manifest as early as the fourth decade of life [2,3].Alpha1-PI protects the lung from damage by proteolytic enzymes (particularly neutrophil elastase) due to its action as an inhibitor of seri