A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Metopimazine Mesylate (NG101) in Participants with Gastroparesis

Background: There is an urgent need for effective and safe treatment of gastroparesis. Metopimazine, a selective, peripherally restricted dopamine D₂ receptor antagonist, is used in France for the symptomatic treatment of nausea and vomiting and chemotherapy-induced nausea and vomiting. Aim: To assess the safety and efficacy of oral NG101, the mesylate salt of metopimazine, for the treatment of gastroparesis. Methods: We conducted a 12-week phase 2 multicenter trial with NG101 5, 10, and 20 mg 4 times a day versus placebo. The primary endpoint was the change in mean nausea severity from the Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary (DIGS-DD) during weeks 7-12 of the Treatment Period from baseline. The DIGS-DD measured nausea, abdominal pain, early satiety, postprandial fullness, and vomiting at their worst in the past 24 hours using a 0 to 10-point numeric rating scale. Patient Global Impression of Change (PGI-C) questionnaires, including nausea, were assessed weekly using a 7-point balanced ordinal score. Results: Of 161 randomized participants (45.3% diabetic and 54.7% idiopathic), mean DIGS-DD nausea severity scores decreased from baseline during Weeks 7-12 in all treatment groups, but these improvements were not statistically significant compared to placebo. However, there were statistically significant improvements in nausea PGI-C during Weeks 1-12 for all treatment groups compared with placebo. Trends in safety and efficacy favored patients with idiopathic gastroparesis compared to those with diabetic gastroparesis. Conclusion: While NG101 did not meet statistical significance in its primary endpoint for reducing nausea severity, it demonstrated a favorable safety profile and significant improvement in some secondary endpoints. Further study is needed to determine if NG101 is an effective treatment for patients with idiopathic gastroparesis.