Metoclopramide Nasal Spray Reduces Symptoms of Gastroparesis in Women, but not Men, With Diabetes: Results of a Phase 2B Randomized Study

• Published in: Clinical gastroenterology and hepatology Vol. 13; no. 7; pp. 1256 - 1263.e1
• Main Authors: Parkman, Henry P., Carlson, Marilyn R., Gonyer, Dave
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Emetic; Antiemetics - administration & dosage; Delayed Gastric Emptying; Diabetes Complications - drug therapy; Double-Blind Method; Female; Gastroenterology and Hepatology; Gastroparesis - drug therapy; Gender; Humans; Male; Metoclopramide - administration & dosage; Middle Aged; Nasal Sprays; Placebos; Prokinetic Agent; Sex Factors; Treatment Outcome; Young Adult; OTE; FDA; GI; SDS; AE; IN; ITT; DM; Gender; Prokinetic Agent; IVRS; mGCSI–DD; Delayed Gastric Emptying; PAGI–SYM; TEAE; Anti-Emetic; OGS; GCSI–DD; PK; diabetes mellitus; overall gastroparesis symptom severity; intention-to-treat; Sheehan Disability Scale; treatment-emergent adverse effects; pharmacokinetic; Food and Drug Administration; overall treatment effect; adverse event; modified Gastroparesis Cardinal Symptom Index–Daily Dairy; Gastroparesis Cardinal Symptom Index–Daily Dairy; gastrointestinal; interactive voice response system; intranasal; Patient Assessment of Upper Gastrointestinal Disorders Symptoms
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2014.12.030

Metoclopramide nasal spray, unlike oral tablets, is absorbed even when patients have delayed gastric emptying or nausea and vomiting. We performed a randomized phase 2b study to evaluate the efficacy and safety of 10-mg and 14-mg metoclopramide nasal spray vs placebo in patients with diabetes and gastroparesis. We performed a multicenter, double-blind study of 285 subjects (71% female) with type 1 or type 2 diabetes and a previous diagnosis of gastroparesis. Subjects were assigned randomly to groups given metoclopramide nasal spray (10 or 14 mg) or placebo 30 minutes before meals and bedtime for 28 days. The primary end point was the change in total symptom score from baseline to week 4, based on symptom items (nausea, bloating, early satiety, and upper abdominal pain) reported in daily diaries. We performed a prespecified subgroup analysis of male vs female subjects. Subjects given metoclopramide nasal spray had an overall reduction in symptom scores, although there was no statistically significant difference in reduction between the metoclopramide groups and the placebo group. Gastroparesis symptom scores were reduced significantly in female subjects given either dose of metoclopramide compared with placebo (mean reduction from 10-mg dose, 1.2 ± 1.18; P = .0247; mean reduction from 14-mg dose, 1.3 ± 0.94; P = .0215). In men, symptom scores decreased more in the placebo group than the metoclopramide groups. The most common treatment-emergent adverse effects were dysgeusia, headache, and fatigue. Metoclopramide nasal spray reduces symptoms of gastroparesis in women, but not in men, with diabetes. Patient sex therefore might be considered in the selection of treatment for diabetic gastroparesis. ClinicalTrials.gov no: NCT00845858.