The Efficacy of Tradipitant in Patients with Diabetic and Idiopathic Gastroparesis in Phase III Randomized Placebo-Controlled Clinical Trial.
GCSI
NK-1
RCT
diabetes
gastroparesis
nausea
vomiting
Journal
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775
Informations de publication
Date de publication:
16 Jan 2024
16 Jan 2024
Historique:
received:
29
09
2023
revised:
13
12
2023
accepted:
02
01
2024
medline:
19
1
2024
pubmed:
19
1
2024
entrez:
18
1
2024
Statut:
aheadofprint
Résumé
Neurokinin receptor 1 (NK1R) antagonists are effective in reducing nausea and vomiting in chemo-therapy induced emesis. We investigated the safety and efficacy of tradipitant, an NK1R antagonist, in patients with idiopathic and diabetic gastroparesis. 201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. Blood levels were monitored for an exposure-response analysis. The primary outcome was change from baseline to week 12 in average nausea severity, measured by daily symptom diary. The ITT population did not meet the pre-specified primary endpoint at Week 12 (difference in nausea severity change drug vs. placebo, P = .741) or pre-specified secondary endpoints. Post hoc analyses were performed to control for drug exposure, rescue medications, and baseline severity inflation. Subjects with high blood levels of tradipitant significantly improved average nausea severity beginning at early time points Weeks 2 through Week 4. In post hoc sensitivity analyses, tradipitant treatment demonstrated strengthened effects, with statistically significant improvements in nausea at Week 12. Although tradipitant did not reach significance in the ITT population, a pharmacokinetic exposure-response analysis demonstrated significant effects with adequate tradipitant exposure. When accounting for confounding factors such as baseline severity inflation and rescue medication, a statistically significant effect was also observed. These findings suggest that tradipitant has potential as a treatment for the symptom of nausea in gastroparesis. [ClincialTrials.gov number, NCT04028492].
Sections du résumé
BACKGROUND
BACKGROUND
Neurokinin receptor 1 (NK1R) antagonists are effective in reducing nausea and vomiting in chemo-therapy induced emesis. We investigated the safety and efficacy of tradipitant, an NK1R antagonist, in patients with idiopathic and diabetic gastroparesis.
METHODS
METHODS
201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. Blood levels were monitored for an exposure-response analysis. The primary outcome was change from baseline to week 12 in average nausea severity, measured by daily symptom diary.
RESULTS
RESULTS
The ITT population did not meet the pre-specified primary endpoint at Week 12 (difference in nausea severity change drug vs. placebo, P = .741) or pre-specified secondary endpoints. Post hoc analyses were performed to control for drug exposure, rescue medications, and baseline severity inflation. Subjects with high blood levels of tradipitant significantly improved average nausea severity beginning at early time points Weeks 2 through Week 4. In post hoc sensitivity analyses, tradipitant treatment demonstrated strengthened effects, with statistically significant improvements in nausea at Week 12.
CONCLUSIONS
CONCLUSIONS
Although tradipitant did not reach significance in the ITT population, a pharmacokinetic exposure-response analysis demonstrated significant effects with adequate tradipitant exposure. When accounting for confounding factors such as baseline severity inflation and rescue medication, a statistically significant effect was also observed. These findings suggest that tradipitant has potential as a treatment for the symptom of nausea in gastroparesis. [ClincialTrials.gov number, NCT04028492].
Identifiants
pubmed: 38237696
pii: S1542-3565(24)00050-8
doi: 10.1016/j.cgh.2024.01.005
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT04028492']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.