Inhaled alpha1-proteinase inhibitor therapy in patients with cystic fibrosis

J Cyst Fibros. 2016 Mar;15(2):227-33. doi: 10.1016/j.jcf.2015.07.009. Epub 2015 Aug 28.

Abstract

Background: Inhaled alpha1-proteinase inhibitor (PI) is known to reduce neutrophil elastase burden in some patients with CF. This phase 2a study was designed to test inhaled Alpha-1 HC, a new aerosolized alpha1-PI formulation, in CF patients.

Methods: We performed a randomized, double-blind, placebo-controlled study and evaluated the safety of 100 or 200mg of inhaled Alpha-1 HC once daily for 3 weeks in subjects with CF. Thirty adult subjects were randomized in a 2:1 ratio to receive Alpha-1 HC or placebo.

Results: Drug delivery was confirmed by a dose-dependent increase in the sputum alpha1-PI. Seven (20.0%) of the 35 adverse events in the 100-mg dose group, 3 (13.0%) of 23 in the 200-mg dose group, and 4 (14.3%) of 28 in the placebo group were drug-related in these subjects. One serious adverse event occurred in 1 subject within each group.

Conclusions: Alpha-1 HC inhalation was safe and well tolerated.

Keywords: Alpha-1 HC; Alpha-1 antitrypsin; Cystic fibrosis; Prolastin.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Leukocyte Elastase / blood
  • Male
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / pharmacokinetics
  • Sputum / metabolism
  • Time Factors
  • Treatment Outcome
  • alpha 1-Antitrypsin / administration & dosage*
  • alpha 1-Antitrypsin / pharmacokinetics

Substances

  • Serine Proteinase Inhibitors
  • alpha 1-Antitrypsin
  • Leukocyte Elastase