Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study

Dicpinigaitis, Peter V.; Morice, Alyn H.; Smith, Jaclyn A.; Sher, Mandel R.; Vaezi, Michael; Guilleminault, Laurent; Niimi, Akio; Gude, Kerstin; Krahn, Ulrike; Saarinen, Riitta; Pires, Philippe Vieira; Wosnitza, Melanie; McGarvey, Lorcan

Abstract

Introduction: The PAGANINI study evaluated the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough (RCC). Methods: PAGANINI was a randomized, double-blind, parallel-group, placebo-controlled, multicenter, dose-finding, phase 2b study. Adults with RCC lasting ≥ 12 months and cough severity ≥ 40 mm on a visual analog scale at screening were enrolled. Participants were randomized 1:1:1:1 to twice-daily 25 mg, 75 mg, or 150 mg oral eliapixant or placebo for 12 weeks. The primary endpoint was change from baseline in 24-h cough count after 12 weeks of intervention. Results: Overall, 310 participants were randomized to twice-daily eliapixant 25 mg (n = 75), 75 mg (n = 78), 150 mg (n = 80), or placebo (n = 77). A statistically significant dose–response signal with eliapixant was detected for the primary endpoint (all dose–response models, adjusted p < 0.1; one-sided). Adverse events (AEs) were reported in 39 (51%) participants with placebo and 43–51 (57–65%) participants receiving eliapixant. The most common AE was dysgeusia, occurring in 1% (n = 1) of the placebo group and 1–16% (n = 1–13) of the eliapixant groups in a dose-related manner. One case of a moderate drug-induced liver injury occurred in a participant receiving 150 mg twice-daily eliapixant. Conclusion: Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG. Trial Registration: ClinicalTrials.gov identifier NCT04562155; registered September 18, 2020.

Citation

Dicpinigaitis, P. V., Morice, A. H., Smith, J. A., Sher, M. R., Vaezi, M., Guilleminault, L., …McGarvey, L. (2023). Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study. Lung, 201, Article 255-266. https://doi.org/10.1007/s00408-023-00621-x

• Journal Article Type: Article
• Acceptance Date: Apr 19, 2023
• Online Publication Date: Jun 1, 2023
• Publication Date: Jun 1, 2023
• Deposit Date: Jul 16, 2023
• Publicly Available Date: Jun 2, 2024
• Journal: Lung
• Print ISSN: 0341-2040
• Electronic ISSN: 1432-1750
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 201
• Article Number: 255-266
• DOI: https://doi.org/10.1007/s00408-023-00621-x
• Keywords: Chronic cough; Eliapixant; P2X3 receptor antagonist; Phase 2b clinical trial
• Public URL: https://hull-repository.worktribe.com/output/4313702