Efficacy and safety of eliapixant in endometriosis-associated pelvic pain: the randomized, placebo-controlled phase 2b SCHUMANN study.
Eliapixant
Endometriosis-associated pelvic pain
P2X3 receptor antagonist
Phase 2b clinical trial
Journal
BMC women's health
ISSN: 1472-6874
Titre abrégé: BMC Womens Health
Pays: England
ID NLM: 101088690
Informations de publication
Date de publication:
19 Jun 2024
19 Jun 2024
Historique:
received:
05
12
2023
accepted:
06
06
2024
medline:
19
6
2024
pubmed:
19
6
2024
entrez:
18
6
2024
Statut:
epublish
Résumé
The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP). SCHUMANN was a randomized, placebo- and active comparator-controlled, double-blind to placebo and open-label to comparator, parallel-group, multicenter, dose-finding phase 2b study. The participants were women with surgically diagnosed endometriosis who fulfilled defined EAPP criteria. Participants were randomized 1:1:1:1 to twice daily (BID) 25 mg, 75 mg, or 150 mg oral eliapixant or a placebo for 12 weeks. An exploratory once-daily elagolix 150 mg treatment group was also included. The primary endpoint was the absolute change in mean worst EAPP from baseline to the end of intervention (EOI). Overall, 215 participants were randomized for treatment (44 to eliapixant 25 mg, 44 to eliapixant 75 mg, 43 to eliapixant 150 mg, 43 to a placebo, and 41 to elagolix 150 mg). For safety reasons, the study was terminated early; both treatment and enrollment stopped immediately, producing less than 50% of the planned number of completers. The study found no significant differences in EAPP reduction from baseline between groups and no significant dose-response model. The elagolix 150 mg group showed better pain reduction than any of the other groups. No new safety signals were observed, relative to the previously known safety profile of eliapixant, which was generally well tolerated. However, one case of moderate and probably drug-induced liver injury in a participant receiving eliapixant 150 mg BID supported the association between eliapixant and a potential increase in liver function values, defined before the start of the phase 2 program. This study did not meet its primary objective as no statistically significant or clinically relevant differences in changes of mean worst EAPP from baseline were observed between treatment groups. The single observed case of moderate, probably drug-induced liver injury was the second case in the eliapixant phase 2 program conducted in the following indications: refractory or unexplained chronic cough, diabetic neuropathic pain, overactive bladder, and EAPP. Due to this, the benefit-risk ratio for the study was no longer considered to be positive. ClinicalTrials.gov identifier NCT04614246; registered November 3, 2020.
Sections du résumé
BACKGROUND
BACKGROUND
The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP).
METHODS
METHODS
SCHUMANN was a randomized, placebo- and active comparator-controlled, double-blind to placebo and open-label to comparator, parallel-group, multicenter, dose-finding phase 2b study. The participants were women with surgically diagnosed endometriosis who fulfilled defined EAPP criteria. Participants were randomized 1:1:1:1 to twice daily (BID) 25 mg, 75 mg, or 150 mg oral eliapixant or a placebo for 12 weeks. An exploratory once-daily elagolix 150 mg treatment group was also included. The primary endpoint was the absolute change in mean worst EAPP from baseline to the end of intervention (EOI).
RESULTS
RESULTS
Overall, 215 participants were randomized for treatment (44 to eliapixant 25 mg, 44 to eliapixant 75 mg, 43 to eliapixant 150 mg, 43 to a placebo, and 41 to elagolix 150 mg). For safety reasons, the study was terminated early; both treatment and enrollment stopped immediately, producing less than 50% of the planned number of completers. The study found no significant differences in EAPP reduction from baseline between groups and no significant dose-response model. The elagolix 150 mg group showed better pain reduction than any of the other groups. No new safety signals were observed, relative to the previously known safety profile of eliapixant, which was generally well tolerated. However, one case of moderate and probably drug-induced liver injury in a participant receiving eliapixant 150 mg BID supported the association between eliapixant and a potential increase in liver function values, defined before the start of the phase 2 program.
CONCLUSIONS
CONCLUSIONS
This study did not meet its primary objective as no statistically significant or clinically relevant differences in changes of mean worst EAPP from baseline were observed between treatment groups. The single observed case of moderate, probably drug-induced liver injury was the second case in the eliapixant phase 2 program conducted in the following indications: refractory or unexplained chronic cough, diabetic neuropathic pain, overactive bladder, and EAPP. Due to this, the benefit-risk ratio for the study was no longer considered to be positive.
CLINICAL TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov identifier NCT04614246; registered November 3, 2020.
Identifiants
pubmed: 38890641
doi: 10.1186/s12905-024-03188-8
pii: 10.1186/s12905-024-03188-8
doi:
Substances chimiques
elagolix
5B2546MB5Z
Hydrocarbons, Fluorinated
0
Pyrimidines
0
Banques de données
ClinicalTrials.gov
['NCT04614246']
Types de publication
Journal Article
Randomized Controlled Trial
Clinical Trial, Phase II
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
353Subventions
Organisme : Bayer AG
ID : N/A
Organisme : Bayer AG
ID : N/A
Organisme : Bayer AG
ID : N/A
Organisme : Bayer AG
ID : N/A
Informations de copyright
© 2024. The Author(s).
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