TY - JOUR
T1 - Efficacy and Safety of Eliapixant in Refractory Chronic Cough
T2 - The Randomized, Placebo-Controlled Phase 2b PAGANINI Study
AU - PAGANINI Investigators
AU - Dicpinigaitis, Peter V
AU - Morice, Alyn H
AU - Smith, Jaclyn A
AU - Sher, Mandel R
AU - Vaezi, Michael
AU - Guilleminault, Laurent
AU - Niimi, Akio
AU - Gude, Kerstin
AU - Krahn, Ulrike
AU - Saarinen, Riitta
AU - Pires, Philippe Vieira
AU - Wosnitza, Melanie
AU - McGarvey, Lorcan
N1 - © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - Adult
KW - Humans
KW - Cough/drug therapy
KW - Carcinoma, Renal Cell
KW - Double-Blind Method
KW - Treatment Outcome
KW - Kidney Neoplasms
KW - Chronic cough
KW - Eliapixant
KW - Phase 2b clinical trial
KW - P2X3 receptor antagonist
UR - http://www.scopus.com/inward/record.url?scp=85160918680&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/3cd640b4-f4fd-3730-92c3-d49c370f3fa6/
U2 - 10.1007/s00408-023-00621-x
DO - 10.1007/s00408-023-00621-x
M3 - Article
C2 - 37261531
SN - 0341-2040
VL - 201
SP - 255
EP - 266
JO - Lung
JF - Lung
IS - 3
ER -