Safety and tolerability of an intravenously administered alpha1-proteinase inhibitor at an increased infusion rate: A novel, randomized, placebo-masked, infusion rate-controlled, crossover study in healthy adults

Abstract

Purpose: Alpha1-proteinase inhibitor (A1PI) is indicated for chronic augmentation therapy in adults with emphysema due to congenital deficiency of A1PI. An intravenous infusion rate of 0.04 mL/kg/minute is currently recommended for the A1PI product, Glassia®. This randomized, placebo-masked, rate-controlled, crossover study was designed to evaluate the safety and tolerability of A1PI administration at an increased infusion rate. Patients and methods: A total of 30 healthy male and female subjects aged 19-61 years were enrolled. Each subject received simultaneous intravenous infusions of A1PI (Glassia®) and placebo (human albumin 2.5%) administered through a single infusion site on two separate treatment periods. Subjects were randomized in a 1:1 ratio to receive either test treatment (A1PI 0.2 mL/kg/minute + placebo 0.04 mL/kg/minute), or reference treatment (A1PI 0.04 mL/kg/minute + placebo 0.2 mL/kg/minute) on Day 1. On Day 15, subjects received the other treatment regimen in a crossover sequence. Results: A total of 36 adverse events (AEs), regardless of causality, were reported; all were non-serious and of mild intensity, with headaches and dizziness occurring most frequently (12 [33.3%] and three [8.3%] of 36 AEs, respectively). Only seven AEs in six subjects were assessed as related to study treatment: with two AEs reported in two subjects treated with the 0.2 mL/kg/minute rate compared with five AEs in four subjects treated with the 0.04 mL/kg/minute rate. Conclusions: This study demonstrated the safety and tolerability of an A1PI product at an increased infusion rate (0.2 mL/kg/minute) resulting in a shorter infusion duration in healthy subjects. © 2014 Ngo et al.