In:
European Respiratory Journal, European Respiratory Society (ERS), Vol. 59, No. 2 ( 2022-02), p. 2100746-
Abstract:
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-CF TM 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 (ppFEV 1 ) 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% ppFEV 1 , 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.
Type of Medium:
Online Resource
ISSN:
0903-1936
,
1399-3003
DOI:
10.1183/13993003.00746-2021
DOI:
10.1183/13993003.00746-2021.Supp1
DOI:
10.1183/13993003.00746-2021.Shareable1
Language:
English
Publisher:
European Respiratory Society (ERS)
Publication Date:
2022
detail.hit.zdb_id:
2834928-3
detail.hit.zdb_id:
1499101-9
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