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

Authors


Address for Correspondence
Dr. Franck Rousseau, Tranzyme, Inc., 5001 S. Miami Blvd., Suite 300, Durham, NC, USA.
Tel: +1 919 328 1111; fax +919 474 0025; e-mail: frousseau@tranzyme.com

Abstract

Background  Gastroparesis causes significant morbidity and treatment options are limited. TZP-102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double-blind, placebo-controlled trial in patients with diabetic gastroparesis.

Methods  A total of 92 outpatients were randomized to once-daily administrations of 10-mg (= 22), 20-mg (= 21), 40-mg (= 23) TZP-102 or placebo (= 26). The primary endpoint was the change from baseline in gastric half-emptying time (T½) utilizing 13C-breath test methodology and secondary endpoints included symptom improvement using patient-reported gastroparesis symptom scores (PAGI-SYM questionnaire) and patient and physician overall treatment evaluations (OTE).

Key Results  Gastric T½ changes were not statistically significant between TZP-102 and placebo after 28 days of treatment at any dose. Clinical improvements (−1.0 to −1.4 point mean decrease in symptom severity) occurred in the Gastroparesis Cardinal Symptom Index (GCSI) component of the PAGI-SYM, which was significant vs placebo for all TZP-102 doses combined. Improvements became evident after 1 week of treatment. Significantly, more patients given TZP-102 (any dose) had a 50% reduction in baseline GCSI score (28.8%vs 7.7% placebo). Safety profiles were similar across groups. All TZP-102 doses were well-tolerated with no adverse cardiac, weight, or glucose control outcomes.

Conclusions & Inferences  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.

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