Efficacy and Safety of Cinitapride in the Treatment of Mild to Moderate Postprandial Distress Syndrome-predominant Functional Dyspepsia

Goals and Background: Functional dyspepsia (FD) is a complex disease with a variety of dyspeptic symptoms. Little is known about the clinical efficacy of cinitapride, a 5-HT4 agonist and D2 antagonist, in treating FD. Study: This randomized, double-blind, double-dummy, positive controlled study compared the efficacy and safety of cinitapride(1 mg) and domperidone (10 mg) tid for 4 weeks in 383 consecutive patients with mild to moderate, postprandial distress syndrome-predominant dyspeptic symptoms according to Rome III criteria. The primary endpoint was the noninferiority of cinitapride compared with domperidone in relief of symptoms. The overall patient evaluation of treatment and open gastric emptying effects of both drugs were treated as the secondary endpoints. Results: The rates of symptom relief by cinitapride and domperidone after 4 weeks did not differ significantly on intension-to-treat analysis (85.8% vs. 81.8%, P=0.332). Cinitapride significantly reduced the overall severity of postprandial fullness, early satiation, and bloating (4.3 +/- 3.9 vs. 17.8 +/- 6.6, P<0.001); and it was superior to the effects of domperidone (5.4 +/- 4.9 vs. 18.4 +/- 6.9, P<0.001; P=0.021 between groups). Cinitapride also decreased the mean half-gastric emptying time from 131.1 +/- 119.4 to 86.5 +/- 18.7 minutes (P=0.0002). There was a positive relationship between symptoms and gastric emptying time (r=0.332, P=0.041). Cinitapride-related adverse events were observed in 9.1% of patients, including 1 patient with extrapyramidal symptoms. No patient experienced QT interval prolongation. Conclusions: This phase III trial has confirmed a noninferior efficacy of cinitapride over domperidone for patients with mild to moderate, postprandial distress syndrome-predominant FD. Cinitapride usage is well tolerated, but its cardiovascular events need further evaluation (NCT 01355276).