A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough DOI Creative Commons
Akio Niimi, Hironori Sagara, Masashi Kikuchi

et al.

Allergology International, Journal Year: 2022, Volume and Issue: 71(4), P. 498 - 504

Published: June 23, 2022

In two phase 3, global clinical trials (COUGH-1 and COUGH-2), the P2X3-receptor antagonist gefapixant significantly reduced objective 24-h cough frequency in participants with refractory or unexplained chronic (RCC UCC) at a dosage of 45 mg twice daily (BID), an acceptable safety profile. The primary this randomized, double-blind, parallel-group study was to assess tolerability Japanese RCC UCC (ClinicalTrials.gov, NCT03696108; JAPIC-CTI, 184154).Participants aged ≥20 years lasting ≥4 months diagnosis despite treatment accordance Respiratory Society guidelines were randomized 1:1 receive 15 BID for 52 weeks. evaluate gefapixant, including adverse events (AEs) discontinuations due AEs. Cough-specific quality life assessed using Leicester Cough Questionnaire as secondary objective.Of 169 treated participants, 63% female mean age 58 years. Adverse reported by 79 (94%) 82 (96%) 15- 45-mg groups, respectively. Most treatment-related AEs taste related. Discontinuations occurred 6 (7%) 17 (20%) receiving BID, There no serious deaths. total scores improved from baseline through Week 52.Gefapixant had profile, participants.

Language: Английский

British Thoracic Society Clinical Statement on chronic cough in adults DOI Open Access
Sean Parker, John A. Smith, Surinder S. Birring

et al.

Thorax, Journal Year: 2023, Volume and Issue: 78(Suppl 6), P. s3 - s19

Published: Dec. 1, 2023

### Terminology, epidemiology and impact Causes of CC Clinical assessment Treatable traits in cough #### Smoking ACEI treatment Airway disease: productive Eosinophilic airway disease

Language: Английский

Citations

39
Neuropathic pain: Mechanisms and therapeutic strategies DOI Creative Commons
Georg Petroianu, Lujain Aloum, Abdu Adem

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 16, 2023

The physiopathology and neurotransmission of pain are an owe inspiring complexity. Our ability to satisfactorily suppress neuropathic or other forms chronic is limited. number pharmacodynamically distinct clinically available medications low the successes achieved modest. Pain Medicine practitioners confronted with ethical dichotomy imposed by Hippocrates: On one hand mandate primum non nocere , on hand, promise heavenly joys if successful divinum est opus sedare dolorem . We briefly summarize concepts associated nociceptive from input (afferents periphery), modulatory output [descending noradrenergic (NE) serotoninergic (5-HT) fibers] local control. control comprised “ inflammatory soup ” at site origin synaptic relay stations, ATP-rich environment promoting inflammation nociception while adenosine-rich having opposite effect. Subsequently, we address transition nociceptor (independent activation) process sensitization chronification (transient progressing into persistent pain). Having sketched a model perception processing attempt identify sites modes action drugs used in treatment, focusing adjuvant (co-analgesic) medication.

Language: Английский

Citations

35
The P2X3 receptor antagonist filapixant in patients with refractory chronic cough: a randomized controlled trial DOI Creative Commons
Christian Friedrich,

Klaus Francke,

Surinder S. Birring

et al.

Respiratory Research, Journal Year: 2023, Volume and Issue: 24(1)

Published: April 11, 2023

Abstract Background P2X3 receptor antagonists seem to have a promising potential for treating patients with refractory chronic cough. In this double-blind, randomized, placebo-controlled study, we investigated the efficacy, safety, and tolerability of novel selective antagonist filapixant (BAY1902607) in Methods Following crossover design, 23 cough (age: 60.4 ± 9.1 years) received ascending doses one period (20, 80, 150, 250 mg, twice daily, 4-days-on/3-days-off) placebo other. The primary efficacy endpoint was 24-h frequency on Day 4 each dosing step. Further, subjective severity health-related quality life were assessed. Results Filapixant at ≥ 80 mg significantly reduced improved life. Reductions over ranged from 17% (80 dose) 37% (250 dose), reductions baseline 23% mg) 41% (placebo: 6%). ratings 100-mm visual analog scale 8 mm 21 mg). No serious or severe adverse events leading discontinuation treatment reported. Taste-related occurred 4%, 13%, 43%, 57% treated 20, respectively, 12% placebo. Conclusions proved be efficacious, safe, and—apart occurrence taste disturbances, especially higher dosages—well tolerated during short therapeutic intervention. Clinical trial registration EudraCT, eudract.ema.europa.eu, 2018-000129-29; ClinicalTrials.gov, NCT03535168

Language: Английский

Citations

24
Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study DOI Open Access
Peter V. Dicpinigaitis, Alyn H. Morice, John A. Smith

et al.

Lung, Journal Year: 2023, Volume and Issue: 201(3), P. 255 - 266

Published: June 1, 2023

Language: Английский

Citations

22
Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough DOI
Elena Kum,

Matthew Patel,

Nermin Diab

et al.

JAMA, Journal Year: 2023, Volume and Issue: 330(14), P. 1359 - 1359

Published: Sept. 11, 2023

Importance Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. Objective To evaluate the efficacy and tolerability of gefapixant treatment adults Data Sources MEDLINE, Embase, Cochrane Central Register Controlled Trials, Web Science from November 2014 to July 2023. Study Selection Two reviewers independently screened parallel crossover randomized clinical trials (RCTs) that compared, in cough, either placebo, 2 more doses without placebo. Extraction Synthesis extracted data. A frequentist random-effects dose-response meta-analysis pairwise was used each outcome. The GRADE (Grading Recommendations, Assessment, Development, Evaluation) approach rate certainty whether would perceive effects as important (greater than minimal difference [MID]) small (less MID). Main Outcomes Measures Cough frequency (measured using VitaloJAK cough monitor; MID, 20%), severity 100-mm visual analog scale [VAS]; higher score is worse; 30 mm), cough-specific quality life Leicester Questionnaire [LCQ]; range, 3 [maximal impairment] 21 [no impairment]; 1.3 points), treatment-related adverse events, events leading discontinuation, taste-related events. Results Nine RCTs including 2980 were included primary analysis. Compared (45 mg twice daily) had on awake (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), VAS (mean difference, −6.2 mm −4.1 −8.4]; high LCQ 1.0 points 0.7-1.4]; certainty). probably caused increase (32 per 100 13-64 more], certainty) 22-46 High-certainty evidence suggests (15 (6 5-8 more]). Conclusions Relevance orally led modest improvements frequency, severity, but increased

Language: Английский

Citations

20
Cough Reflex Hypersensitivity as a Key Treatable Trait DOI
Woo‐Jung Song, Deepti Vellaichamy Manian,

Yeon-Hee Kim

et al.

The Journal of Allergy and Clinical Immunology In Practice, Journal Year: 2024, Volume and Issue: 13(3), P. 469 - 478

Published: Nov. 16, 2024

Language: Английский

Citations

8
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough DOI Creative Commons
Lorcan McGarvey, John A. Smith, Alyn H. Morice

et al.

Lung, Journal Year: 2022, Volume and Issue: 201(1), P. 25 - 35

Published: Dec. 13, 2022

Abstract Introduction To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC). Methods In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, 300 mg placebo once daily 4 weeks. The primary endpoint was change from baseline in 24-h frequency (coughs/h) with vs placebo. Results Overall, 390/406 randomized completed study. Placebo-adjusted changes hourly count over 24 h were 13.17% ( P = 0.3532), − 1.77% 0.8935), and 12.47% 0.3241) severity (visual analog scale) 1.75 mm 0.5854), 1.21 0.7056), 6.55 0.0433) mg, respectively. Leicester Cough Questionnaire total scores 0.37 0.4207), 0.07 0.8806), 0.69 0.1473) Additionally, 61.3%, 78.3%, 86.8%, 71.4% receiving placebo, respectively, reported any improvements Patient Global Impression Change. incidence treatment-emergent adverse events (TEAEs) 25.7%, 32.0%, 49.0%, 20.6% groups, respectively; all TEAEs group mild-to-moderate. Conclusion Sivopixant did not demonstrate statistically significant difference frequency. has potential RCC/UCC, showing greatest patient-reported outcomes dose-related mild to moderate reversible taste disturbance, although further trials are needed. Clinical Trial Registration ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.

Language: Английский

Citations

29
The Therapeutic Landscape in Chronic Cough DOI Creative Commons
John A. Smith

Lung, Journal Year: 2023, Volume and Issue: 202(1), P. 5 - 16

Published: Dec. 21, 2023

Abstract In recent years, there has been a substantial increase in the development of antitussive therapies and first new therapy, gefapixant licenced Europe. This review describes current unlicenced treatments for chronic cough details currently refractory idiopathic pulmonary fibrosis, as well compounds previously explored.

Language: Английский

Citations

16
Benefit-Risk Profile of P2X3 Receptor Antagonists for Treatment of Chronic Cough DOI
Shota Yamamoto, Nobuyuki Horita, Johsuke Hara

et al.

CHEST Journal, Journal Year: 2024, Volume and Issue: 166(5), P. 1124 - 1140

Published: June 8, 2024

Language: Английский

Citations

6
ATP, an attractive target for the treatment of refractory chronic cough DOI Creative Commons
Mengru Zhang, Dominic L. Sykes, Laura R. Sadofsky

et al.

Purinergic Signalling, Journal Year: 2022, Volume and Issue: 18(3), P. 289 - 305

Published: June 21, 2022

Abstract Chronic cough is the most common complaint in respiratory clinics. Most of them have identifiable causes and some may respond to disease-modifying therapies. However, there are many patients whose lacks effective aetiologically targeted treatments or remains unexplained after thorough assessments, which been described as refractory chronic cough. Current for limited often accompanied by intolerable side effects such sedation. In recent years, various in-depth researches into pathogenesis led an explosion development drugs treatment There has considerable progress underlying mechanisms targeting ATP, ongoing completed clinical studies confirmed promising antitussive efficacy P2X3 antagonists Herein, we review foundation on ATP target was developed potential medications provide update current progresses.

Language: Английский

Citations

20