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

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 (n = 22), 20‐mg (n = 21), 40‐mg (n = 23) TZP‐102 or placebo (n = 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.