• N Ejskjaer, E T Vestergaard, P M Hellström, L C Gormsen, S Madsbad, J L Madsen, T A Jensen, J C Pezzullo, J S Christiansen, L Shaughnessy, and G Kosutic.
• Aarhus University Hospital, Aarhus, Denmark.
• Aliment. Pharmacol. Ther. 2009 Jun 1; 29 (11): 1179-87.

BackgroundTZP-101 is a synthetic, selective ghrelin agonist in development for gastroparesis.AimTo assess safety and effects of TZP-101 in diabetes patients with symptomatic gastroparesis.MethodsAdults with type 1 or type 2 diabetes mellitus received placebo and TZP-101 (80, 160, 320 or 600 microg/kg) infusions in a cross-over manner following a radiolabelled meal. Blood glucose levels were stabilized using a hyperinsulinemic-euglycemic clamp. Primary endpoints were gastric half emptying and latency times. Secondary measures included assessment of gastroparesis symptoms and endocrine responses.ResultsTen patients with type 1 (n = 7) or 2 (n = 3) diabetes, moderate-to-severe gastroparesis symptoms and > or =29% retention 4 h after a radiolabelled solid meal were enrolled. TZP-101 produced significant reductions in solid meal half-emptying (20%, P = 0.043) and latency (34%, P = 0.037) times vs. placebo. Reductions in overall postmeal symptom intensity (24%) and postprandial fullness (37%) following TZP-101 infusion were not statistically significant. Most adverse events were mild and self-limiting and there were no identifiable differences in numbers or types of adverse events between TZP-101 and placebo.ConclusionsThis proof-of-concept study demonstrates that the ghrelin agonist TZP-101 is well-tolerated in diabetes patients with moderate-to-severe chronic gastroparesis and shows statistically significant improvements in gastric emptying.

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