Ghrelin receptor agonist (TZP‐101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis

Abstract

SUMMARYBackground TZP-101 is a synthetic, selective ghrelin agonist in development for gastroparesis.

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

“…Post-hoc analysis of a subset of patients with severe nausea and vomiting (baseline severity score of >3.5 on the GCSI Nausea ⁄ Vomiting subscale) enrolled in this phase 2 study found that nausea and vomiting at the end of treatment (day 4) were significantly reduced for the 80 μg/kg TZP-101 dose compared to placebo and at 30 day follow-up, the improvement of nausea and vomiting appeared to persist for the 80 μg/kg and all TZP-101 dose groups (figure 1), although findings did not reach statistical significance (Table 1) [80]. No significant safety issues were identified in either the multicenter study or subset population, demonstrating TZP-101to be safe and well tolerated with a relatively benign side effect profile [78][79][80].…”

“…TZP-101 (ulimorelin) is a first-in-class macrocyclic ghrelin analogue with potent binding affinity for the ghrelin receptor [77]. Initial investigations of this agent in patients with diabetic gastroparesis were promising with 20% reduction in GE half-time of solids vs. placebo in a proof of concept study with a trend towards decreased overall postprandial symptoms and postprandial fullness (Table 1) [78]. A phase 2 multicenter doseranging study in patients with moderate to severe symptomatic diabetic gastroparesis subsequently demonstrated significant improvements from baseline on day 4 in Gastroparesis Cardinal Symptom Index (GCSI) loss of appetite and vomiting scores with the 80 μg/kg TZP-101 dose when compared to placebo and a 25% improvement in GE half-time for a small subset of combined TZP-101 dose groups compared to a 8% improvement with placebo, although differences in GE T1/2 were not statistically significant (Table 1) [79].…”

Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting - randomised clinical study subset data

“…18,19 Pharmacological doses of exogenous ghrelin have significant GI prokinetic effects in patients with both idiopathic and diabetic gastroparesis. TZP-101 accelerates gastric emptying in adults with diabetic gastroparesis, 20,21 and improves recovery of GI motility following bowel resection. 22 The pharmacokinetics of TZP-101 in patients with gastroparesis and healthy subjects are comparable and there is little accumulation of TZP-101 after multiple dosing.…”

“…23 Administration of TZP-101 is well tolerated and safety profiles are similar in placebo and TZP-101 treatment groups. [20][21][22] In a phase 2 trial in adult patients with type 1 or 2 diabetes, daily intravenous TZP-101 for 4 days demonstrated clinically and statistically significant improvements in several gastroparesis-related symptoms, including nausea and vomiting, postprandial fullness ⁄ early satiety and loss of appetite. 21 This study also showed that a single, daily dose of 80 lg ⁄ kg was the most effective dose.…”

Diabetic gastroparesis: epidemiology, mechanisms of development, modern approaches to the management

“…в последнее время все чаще применяются более современные и безопасные прокинетики, такие как итоприд и прукалоприд [6,9]. Среди новых изучаемых в настоящее время препаратов следует отметить агонисты рецепторов грелина, которые показали способность ускорять опорожнение желудка у больных с диабетическим гастропарезом, а также лечение стволовыми клетками [18]. пока нет препаратов, которые были бы в равной степени эффективны для лечения абдоминальной боли, ассоциированной с замедленным опорожнением желудка.…”