Ghrelin Agonist TZP-101 Improves Symptoms and Gastric Emptying in Diabetic Patients with Gastroparesis

Abstract

Purpose: TZP-101, a ghrelin agonist, has been shown to accelerate gastric emptying (GE) in diabetic patients with gastroparesis (GP) by 4-h scintigraphy. The goal was to evaluate TZP-101 effects on symptoms in diabetic patients with GP. Methods: USA and European Centers participated in a randomized, placebo controlled study of 76 diabetic patients with GP (presence of symptoms & demonstration of delayed GE). For 4 days, patients received a 30 min IV infusion of one of six TZP-101 doses (range 20-600μg/kg) or placebo (57 received TZP-101; 19 received placebo); elective hospitalization; efficacy was evaluated by: Gastroparesis Cardinal Symptom Index (GCSI) - daily; meal-related Gastroparesis Symptom Assessment (GSA) - daily; and Clinician Rated Symptom Assessment (CRSA) - end of treatment; gastric emptying; regular battery of safety assessment tests; 30-day follow up for efficacy and safety. Results: TZP-101 induced gradual symptom improvement over 4 days while placebo showed no change or gradual deterioration (vomiting & early satiety shown). Of all doses, the 80μg/kg dose was the most effective. At the end of dosing (80 μg/kg over placebo) the following symptoms improved significantly/trend toward significance: GCSI: vomiting (p=0.006), loss of appetite (p=0.034), early satiety (p=0.087); sustained effect on vomiting for 30 days (p=0.03); GSA (shown): postprandial fullness (p=0.007); CRSA: early satiety (p=0.089), abdominal distension (p=0.053), bloating (p=0.082). During the 30-day follow-up period, 3% of patients on TZP-101 vs. 10% on placebo were hospitalized due to GP. When GE was reassessed on the day after the 4th infusion, TZP-101 accelerated GE rate by 25% (vs. 8% on placebo); TZP-101 was safe and well tolerated for all doses studied. Conclusion: TZP-101, given IV for 4 consecutive days in diabetic GP patients, had a significant impact on vomiting, loss of appetite and fullness/early satiety as well as GE. Further TZP-101 evaluation in diabetic GP patients is anticipated since the results suggest a number of potential clinical benefits including improved glucose control and better nutrition. This research was supported by an industry grant from Tranzyme, Inc.Figure: Symptoms on day 4 - GSA.