Acotiamide for esophagogastric junction outflow obstruction: Phase II trial

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Created On: 09/10/2026

Esophagogastric junction outflow obstruction

Esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder marked by altered relaxation at the esophagogastric junction, often involving abnormal lower esophageal sphincter (LES) function.

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Key take away

Acotiamide significantly improves lower esophageal sphincter relaxation in patients with esophagogastric junction outflow obstruction, with symptom relief increasing over prolonged treatment.

Background

Acotiamide is a gastrointestinal motility agent previously investigated for disorders including functional dyspepsia. This phase II trial assessed whether targeting impaired LES relaxation with acotiamide could improve physiological and symptomatic outcomes in EGJOO.

Method

This randomized controlled trial enrolled 35 patients with EGJOO. During the initial 4-week placebo-controlled phase, patients were randomized to placebo (n = 11), low-dose acotiamide (300 mg/day, n = 12), or high-dose acotiamide (600 mg/day, n = 12).

In the subsequent 4-week open-label extension phase, all 35 patients received 600 mg/day acotiamide. The key outcome assessed the improvement rate of food-sticking symptoms in the chest over the first 4 weeks. Secondary endpoints included the integrated relaxation pressure (IRP) normalization rate and clinical symptom measures, while exploratory endpoints tracked long-term symptom and physiological changes through week 8.

Result

During the 4-week placebo-controlled period, improvement in food-sticking symptoms in the chest was noted in 12.5% of patients receiving acotiamide versus 0% receiving placebo; however, the between-group difference was not statistically significant. In contrast, acotiamide produced a remarkable improvement in the physiological measure of LES relaxation.

The IRP normalization rate was 41.7% with acotiamide compared with 0% with placebo. No other secondary endpoints illustrated pivotal differences between treatment groups. During the subsequent open-label period, 24 patients who received ≥300 mg/day of acotiamide for 8 weeks were evaluated. The improvement rate for food-sticking symptoms increased to 37.5%, while the IRP normalization rate increased to 54.2%.

Conclusion

Acotiamide proved beneficial at normalizing impaired LES relaxation in EGJOO, as demonstrated by improvements in IRP. While short-term (4-week) primary symptom endpoints did not reach statistical significance, extended 8-week treatment produced progressive clinical improvements in chest food-sticking symptoms, establishing acotiamide as a promising therapeutic option for EGJOO care.