ETD001, a long-acting inhaled ENaC blocker, is well tolerated in a first human, healthy participant trial.
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Authors
Russell P.
Woodward K.
Morris D.
Prasad N.
White R.
Wilkes D.
Gosling M.
Danahay, H.
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Issue Date
2026
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Article
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Abstract
Background Inhibition of the epithelial sodium channel, ENaC, in the airways of people with cystic fibrosis, represents an approach to restore airway mucus hydration and clearance. ETD001 is a novel inhaled ENaC blocker that has been designed to provide long-lasting efficacy. Methods A Phase 1 study was conducted in healthy people evaluating safety, tolerability and pharmacokinetics of ETD001 following single and multiple inhaled ascending doses. Results ETD001 was tolerated at single inhaled doses (0.06 - 10.8 mg), and on repeat dosing for up to 14 days (0.6 - 4.65 mg) twice daily. Adverse events (AE) were balanced across treatment groups, were of mild or moderate severity and had resolved by study completion. Two participants were withdrawn from the study for non-drug related AEs (COVID-19 infection, atrial fibrillation). Two AEs of mild severity were considered possibly related to the study drug: dizziness (placebo participant) and chest discomfort (ETD001; 1.55 mg BID). There was no evidence for ETD001-induced changes in blood potassium levels at any of the doses evaluated. The pharmacokinetic profile of ETD001 was consistent with a slow, sustained absorption out of the lung into the circulation with renal clearance representing a significant pathway for elimination (up to 25% of the nominal dose). Conclusions ETD001 at doses up to and including 4.65 mg twice daily for 14 days was well tolerated in healthy people. The drug was slowly absorbed out of the lung and into the systemic circulation, consistent with prolonged retention in the lung, supporting twice daily dosing during further development. Copyright © 2025 The Authors.
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Journal of Cystic Fibrosis
Volume
25
Issue
2