Long‐term safety and efficacy of acotiamide in functional dyspepsia (postprandial distress syndrome)—results from the European phase 3 open‐label safety trial

Abstract

Backgrounds Acotiamide is a novel acetylcholinesterase inhibitor for treatment of postprandial distress syndrome (PDS) symptoms of functional dyspepsia (FD). This European phase 3 open‐label safety trial has been conducted to evaluate the long‐term safety of acotiamide and explore the efficacy of acotiamide on PDS symptoms using the validated LPDS, quality of life using SF‐36 and SF‐NDI, and work productivity using WPAI. Methods FD‐PDS patients (defined by ROME III criteria) aged ≥18 years with active PDS symptoms and without predominant overlapping symptoms of epigastric pain syndrome and related disorders were enrolled to receive 100 mg acotiamide three times daily for 1 year. Patients' safety profile and efficacy of acotiamide were monitored. Key Results The majority of patients (81.6%) maintained exposure to acotiamide for >50 weeks, with a mean duration of 320.3 days. No specific clinically significant safety concerns have been shown, with no deaths, treatment‐related severe/serious adverse events, or any clinically significant laboratory test results. Although being an open‐label trial, acotiamide showed a change in severity larger than the minimum clinically important difference at weeks 1 and 2 for postprandial fullness and early satiation (meal‐related symptoms), and showed improvement of quality of life and work productivity from the first measurement (at week 12) up to 1 year. Conclusions & Inferences The long‐term safety of acotiamide treatment was confirmed. A clinically important change for PDS symptoms, QoL, and work productivity was suggested; however a controlled trial is required to confirm this hypothetic efficacy of acotiamide. (NCT01973790).

Review article: treatment options for functional dyspepsia

“…Similarly, the elimination rate of postprandial fullness, upper abdominal bloating and early satiation increased to 12% at week 8 and remained stable thereafter . Similar results were obtained in a European single‐arm 52‐week trial, reporting a moderate or strong improvement of symptoms in 70.2% of the patients . The efficacy of acotiamide to reduce FD symptoms is further supported by several other clinical placebo‐controlled trials, reporting a response rate between 31% and 78% after two or more weeks of treatment .…”

Clinical Practice Guidelines for Functional Dyspepsia in Korea

“…92 Acotiamide was also reported to have a significant clinical effect on the quality of life and postprandial symptoms in an open, 3-phase study for long-term outcome and safety. 93 Recently, a study comparing PDS-and EPS-type patients with FD showed that acotiamide significantly improved symptoms in both groups, but in a subgroup analysis, it was found to be more effective against the PDS type. 94 Based on these results, acotiamide would be a good therapeutic agent for patients who primarily have PDS symptoms.…”

Acotiamide affects antral motility, but has no effect on fundic motility, gastric emptying or symptom perception in healthy participants

“…These results were reproduced in several physiological clinical studies in FD patients, showing an improvement of gastric accommodation and gastric emptying rate following acotiamide treatment using scintigraphy, ultrasonography or barostat. 15,19,20 Moreover, acotiamide improved FD symptoms after two or more weeks of treatment in comparison to placebo 14,[20][21][22] and was shown to be more effective in the treatment of PDS than EPS. 8 Mechanistic studies in healthy subjects are limited.…”