Efficacy and safety of inhaled ENaC inhibitor BI 1265162 in patients with cystic fibrosis: BALANCE-CF 1, a randomised, phase II study

Eur Respir J. 2022 Feb 17;59(2):2100746. doi: 10.1183/13993003.00746-2021. Print 2022 Feb.


Background: Inhibition of the epithelial sodium channel (ENaC) in cystic fibrosis (CF) airways provides a mutation-agnostic approach that could improve mucociliary clearance in all CF patients. BI 1265162 is an ENaC inhibitor with demonstrated pre-clinical efficacy and safety already demonstrated in humans.

Objective: We present results from BALANCE-CFTM 1, a phase II, placebo-controlled, randomised, double-blind study of four dose levels of BI 1265162 versus placebo for 4 weeks on top of standard of care in adults and adolescents with CF.

Results: Initially, 28 randomised subjects (BI 1265162 200 µg twice daily n=14, placebo twice daily n=14) were assessed at an interim futility analysis. Compared with placebo, numerical changes of -0.8% (95% CI -6.6 to 4.9%) in percentage predicted forced expiratory volume in 1s (ppFEV1) and +2.1 units (95% CI -2.4 to 6.5 units) in lung clearance index (LCI) were observed in the active group, meeting a pre-defined stopping rule; accordingly, the study was terminated. Recruitment had continued during the interim analysis and pending results; 24 patients were added across three dose levels and placebo. The final results including these patients (+1.5% ppFEV1, 200 µg twice-daily dose versus placebo) were not supportive of relevant clinical effect. Furthermore, LCI change was not supportive, although interpretation was limited due to insufficient traces meeting quality criteria. A 9.4-point improvement in the Cystic Fibrosis Questionnaire - Revised Respiratory Domain was observed in the 200 µg twice daily dose group versus placebo. BI 1265162 up to 200 µg twice daily was safe and well-tolerated. Pharmacokinetics were similar to those in healthy volunteers.

Conclusion: BI 1265162 was safe, but did not demonstrate a potential for clinical benefit. Development has been terminated.

Trial registration: ClinicalTrials.gov NCT04059094.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / drug therapy
  • Double-Blind Method
  • Forced Expiratory Volume
  • Humans
  • Mucociliary Clearance
  • Respiratory Function Tests / methods


  • Cystic Fibrosis Transmembrane Conductance Regulator

Associated data

  • ClinicalTrials.gov/NCT04059094