Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms offunctional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trial

Introduction: Motilin-receptor agonists are prokinetics; whether they relie ve the symptoms of functional dyspepsia is unknown. We aimed to test the ef ficacy of the motilin agonist ABT-229 in functional dyspepsia patients with and without delayed gastric emptying. Methods: Patients were randomized with postprandial symptoms and documented functional dyspepsia by endoscopy (n=589 in intention-to-treat analysis). Patients were assigned to either the delayed or normal gastric emptying str ata, based on a validated C-13 octanoic acid breath test. Patients were the n further randomized within each strata, to receive one of four doses of AB T-229 (1.25, 2.5, 5 or 10 mg b.d. before breakfast and dinner) or placebo f or 4 weeks, following a 2-week baseline. The primary outcome was the assess ment of change in symptom severity over the 2 weeks from baseline to final visit, based on a self-report questionnaire measuring severity on visual an alogue scales. Results: Baseline characteristics across the treatment arms were very simil ar. No significant differences in the upper abdominal discomfort severity s core (maximum 800 mm) were observed for any active treatment arm vs. placeb o (mean change from baseline -139, -141, -145, -160 and -134 mm for placebo , 1.25, 2.5, 5, and 10 mg, respectively, at 4 weeks by intention-to-treat). More patients on placebo reported a good or excellent global response than patients on 1.25 or 5 mg of active therapy (both P < 0.05). The results we re very similar in those with and without delayed gastric emptying. Helicob acter pylori status did not predict response. Excluding patients with any b aseline heartburn (total remaining n=240), ABT-229 10 mg was inferior to pl acebo in relief of upper abdominal discomfort. Conclusions: ABT-229 was of no value for relief of symptoms in functional d yspepsia, compared with placebo.