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

Abstract

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.