Metoclopramide Nasal Spray in Women With Symptomatic Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study

• Published in: Clinical gastroenterology and hepatology Vol. 22; no. 12; pp. 2497 - 2505.e5
• Main Authors: McCallum, Richard W., Parkman, Henry P., Fass, Ronnie, Bhandari, Bal R., Carlson, Marilyn R., Buck, Raymond D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2024
• Subjects: Adolescent; Adult; Aged; Antiemetics - administration & dosage; Antiemetics - adverse effects; Antiemetics - therapeutic use; Diabetes Complications - drug therapy; Diabetic Complications; Double-Blind Method; Female; Gastroenterology and Hepatology; Gastrointestinal; Gastroparesis - drug therapy; Gastropathy; Humans; Metoclopramide - administration & dosage; Metoclopramide - adverse effects; Middle Aged; Nasal Sprays; Neuropathy; Placebos - administration & dosage; Treatment Outcome; United States; Young Adult; United States; FDA; AE; LSM; Diabetic Complications; ITT; CNS; Neuropathy; Gastrointestinal; Gastropathy; TD; ANCOVA; SD; MNS; GSA; TEAEs; intent-to-treat (population); metoclopramide nasal spray; treatment-emergent adverse events; Food and Drug Administration; Gastroparesis Symptom Assessment; adverse events; central nervous system; least squares means; analysis of covariance; standard deviation; tardive dyskinesia
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2023.10.022

Metoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared with placebo in reducing symptoms of diabetic gastroparesis in women. This US multicenter, randomized, double-blind, parallel group study enrolled women aged 18–75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy end point was change in mean daily Gastroparesis Symptom Assessment total score from baseline to Week 4. The Gastroparesis Symptom Assessment daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a 5-point ordinal scale. Two hundred and five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared with the placebo group from baseline to Week 4 (P = .881). However, subjects with moderate-to-severe symptoms at baseline had a significant treatment effect from Weeks 1 to 3 (P < .05) and experienced a significant reduction in nausea and upper abdominal pain for all 4 weeks versus placebo (P < .05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently. Although the primary end point was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate-to-severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. (ClinicalTrials.gov identifier: NCT02025725.) [Display omitted]