A phase 2a, randomized, double‐blind 28‐day study of TZP‐102 a ghrelin receptor agonist for diabetic gastroparesis

Abstract

TZP-102 for 28 days, at doses of 10-40 mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit.

Architectural Organization of the Metabolic Regulatory Enzyme Ghrelin O-Acyltransferase

“…Supporting this possibility, inhibition of GOAT in mice prevented weight gain on a high fat diet and improved glucose control (8) and may represent an attractive target for the treatment of obesity and diabetes. Additionally, ghrelin has been implicated in a host of other physiologic processes, including gastric motility (9,10); learning, memory, and reward behavior (11)(12)(13); cardiovascular function (14 -16); and survival in extreme starvation (17)(18)(19).…”

The relationship between gastric motility and nausea: Gastric prokinetic agents as treatments

“…In animal models of gastroparesis and dyspepsia, ghrelin receptor agonists increase gastric emptying and alleviate anorexia and vomiting (Liu et al, 2006;Rudd et al, 2006;Qiu et al, 2008). In a pilot study with the intravenous ghrelin receptor agonist TZP-101 (Ejskjaer et al, 2010) and a phase IIa trial with TZP-102 (an orally-administered ghrelin receptor agonist; Ejskjaer et al, (2012)) there was some relief from symptoms in patients with diabetic gastroparesis but gastric emptying was unchanged and symptomatic benefit was not maintained in a larger phase IIb trial with TZP-102 and development was stopped (http://ir.tranzyme.com/releasedetail.cfm? ReleaseID=721471).…”

Pharmacological agents currently in clinical trials for disorders in neurogastroenterology

“…The 20-mg TZP-102 dose was superior to placebo for nausea, early satiety, postprandial fullness, bloating, upper abdominal pain, and patient-reported overall treatment effect (21). In patients with baseline gastric emptying t 1/2 exceeding 168 minutes (on 13 C-octanoate breath test), TZP-102 did not accelerate gastric emptying, but it reduced a composite symptom score of nausea, inability to finish meals, upper abdominal pain, and bloating (22). However, in a preliminary report of a randomized, placebo-controlled, 12-week trial of 10 and 20 mg oral TZP-102 in 201 patients with diabetic gastroparesis, there was no significant symptomatic benefit of either dose over placebo (23).…”