Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease : A Randomized Controlled Trial.
Journal
Annals of internal medicine
ISSN: 1539-3704
Titre abrégé: Ann Intern Med
Pays: United States
ID NLM: 0372351
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
pubmed:
8
11
2022
medline:
22
12
2022
entrez:
7
11
2022
Statut:
ppublish
Résumé
Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD. To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation. Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791). Outpatient. 150 patients with PD and constipation. ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period. The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]). The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group ( Longer treatment periods need to be investigated in future studies. ENT-01 was safe and significantly improved constipation. Enterin, Inc.
Sections du résumé
BACKGROUND
Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD.
OBJECTIVE
To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation.
DESIGN
Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791).
SETTING
Outpatient.
PATIENTS
150 patients with PD and constipation.
INTERVENTION
ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period.
MEASUREMENTS
The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]).
RESULTS
The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (
LIMITATION
Longer treatment periods need to be investigated in future studies.
CONCLUSION
ENT-01 was safe and significantly improved constipation.
PRIMARY FUNDING SOURCE
Enterin, Inc.
Banques de données
ClinicalTrials.gov
['NCT03781791']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1666-1674Commentaires et corrections
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