Introduction

Primary ciliary dyskinesia (PCD) is a rare genetic disease with defective ciliary function leading to impaired mucociliary clearance, mucus hyperconcentration, airway inflammation, and lower respiratory tract infections, causing bronchiectasis and progressive lung function decline. There are no clinically proven therapies that improve mucociliary clearance or lung function in PCD.

Objective

The objective of this Phase 2 trial was to evaluate the safety and efficacy of treatment with idrevloride, an epithelial sodium channel (ENaC) inhibitor, in adolescents and adults with PCD. The primary endpoint was absolute change in percent predicted FEV1 (ppFEV1) after 28 days, comparing idrevloride in hypertonic saline (HS) with HS.

Methods

123 people with PCD (pwPCD), age ≥12 years, at 32 sites in 10 countries, were randomized to idrevloride in HS and HS alone, or idrevloride alone and placebo in a 2:2:1:1 ratio in 2-treatment crossovers. Nebulised solutions were administered BID for 28 days in each treatment period. Spirometry was assessed before and after each period.

Results

ppFEV1 improved from baseline following treatment with idrevloride in HS for 28 days compared with HS alone (difference between treatments=1.5%; p=0·044 [95% CI 0·04–3·0]). HS alone or idrevloride alone or placebo did not improve ppFEV1. No increase in serum potassium concentration or post-dose reduction in ppFEV1 was detected. Adverse events were typical of those seen in pwPCD and did not differ between treatment groups.

Conclusion

Short-term inhaled idrevloride in HS was safe and effective for improving lung function in pwPCD. Longer studies are needed.