Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: A randomized, placebo-controlled study

N. Ejskjaer, G. Dimcevski, John Wo, P. M. Hellström, L. C. Gormsen, I. Sarosiek, E. Søfteland, Thomas Nowak, J. C. Pezzullo, L. Shaughnessy, G. Kosutic, R. McCallum

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Abstract

Background Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP-101, is in clinical development for treatment of gastroparesis. This double-blind, randomized, placebo-controlled study evaluated the safety and efficacy of multiple TZP-101 doses in patients with moderate to severe symptomatic diabetic gastroparesis. Methods Patients were admitted to the hospital and adaptively randomized to receive a single 30-min intravenous infusion of 20, 40, 80, 160, 320, or 600 μg kg-1 TZP-101, (n = 57) or placebo, (n = 19) for four consecutive days. Symptoms were evaluated daily with the patient-rated Gastroparesis Cardinal Symptom Index (GCSI) and Gastroparesis Symptom Assessment (GSA). Clinicians rated gastroparesis symptoms on treatment day 4. Key Results The 80 μg kg-1 dose was identified as the most effective dose. On day 4, there was statistically significant improvement compared with placebo in the severity of GCSI Loss of Appetite and Vomiting scores for that dose group (P = 0.034 and P = 0.006). In addition, at the 80 μg kg-1 dose, the proportion of patients with at least 50% improvement in vomiting score was significantly different (P = 0.019) compared with placebo. Meal-related GSA scores for Postprandial fullness were significantly improved in the 80 μg kg-1 TZP-101 group compared with placebo (P = 0.012). Clinicians rated the 80 μg kg-1 group better improved than placebo for overall symptom assessment (P = 0.047). Safety profiles were similar in the placebo and TZP-101 groups and all doses were well-tolerated. Conclusions & Inferences TZP-101 appears to be safe, well-tolerated, and effective at acutely addressing several gastroparesis symptoms.

Original languageEnglish (US)
JournalNeurogastroenterology and Motility
Volume22
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Gastroparesis
Ghrelin
Placebos
Safety
Symptom Assessment
Vomiting
Ghrelin Receptor
ulimorelin
Appetite
Intravenous Infusions
Meals
Stomach
Diabetes Mellitus

Keywords

  • gastric motility
  • gastroparesis management
  • ghrelin

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis : A randomized, placebo-controlled study. / Ejskjaer, N.; Dimcevski, G.; Wo, John; Hellström, P. M.; Gormsen, L. C.; Sarosiek, I.; Søfteland, E.; Nowak, Thomas; Pezzullo, J. C.; Shaughnessy, L.; Kosutic, G.; McCallum, R.

In: Neurogastroenterology and Motility, Vol. 22, No. 10, 10.2010.

Research output: Contribution to journalArticle

Ejskjaer, N, Dimcevski, G, Wo, J, Hellström, PM, Gormsen, LC, Sarosiek, I, Søfteland, E, Nowak, T, Pezzullo, JC, Shaughnessy, L, Kosutic, G & McCallum, R 2010, 'Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: A randomized, placebo-controlled study', Neurogastroenterology and Motility, vol. 22, no. 10. https://doi.org/10.1111/j.1365-2982.2010.01519.x
Ejskjaer, N. ; Dimcevski, G. ; Wo, John ; Hellström, P. M. ; Gormsen, L. C. ; Sarosiek, I. ; Søfteland, E. ; Nowak, Thomas ; Pezzullo, J. C. ; Shaughnessy, L. ; Kosutic, G. ; McCallum, R. / Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis : A randomized, placebo-controlled study. In: Neurogastroenterology and Motility. 2010 ; Vol. 22, No. 10.
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abstract = "Background Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP-101, is in clinical development for treatment of gastroparesis. This double-blind, randomized, placebo-controlled study evaluated the safety and efficacy of multiple TZP-101 doses in patients with moderate to severe symptomatic diabetic gastroparesis. Methods Patients were admitted to the hospital and adaptively randomized to receive a single 30-min intravenous infusion of 20, 40, 80, 160, 320, or 600 μg kg-1 TZP-101, (n = 57) or placebo, (n = 19) for four consecutive days. Symptoms were evaluated daily with the patient-rated Gastroparesis Cardinal Symptom Index (GCSI) and Gastroparesis Symptom Assessment (GSA). Clinicians rated gastroparesis symptoms on treatment day 4. Key Results The 80 μg kg-1 dose was identified as the most effective dose. On day 4, there was statistically significant improvement compared with placebo in the severity of GCSI Loss of Appetite and Vomiting scores for that dose group (P = 0.034 and P = 0.006). In addition, at the 80 μg kg-1 dose, the proportion of patients with at least 50{\%} improvement in vomiting score was significantly different (P = 0.019) compared with placebo. Meal-related GSA scores for Postprandial fullness were significantly improved in the 80 μg kg-1 TZP-101 group compared with placebo (P = 0.012). Clinicians rated the 80 μg kg-1 group better improved than placebo for overall symptom assessment (P = 0.047). Safety profiles were similar in the placebo and TZP-101 groups and all doses were well-tolerated. Conclusions & Inferences TZP-101 appears to be safe, well-tolerated, and effective at acutely addressing several gastroparesis symptoms.",
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AU - Dimcevski, G.

AU - Wo, John

AU - Hellström, P. M.

AU - Gormsen, L. C.

AU - Sarosiek, I.

AU - Søfteland, E.

AU - Nowak, Thomas

AU - Pezzullo, J. C.

AU - Shaughnessy, L.

AU - Kosutic, G.

AU - McCallum, R.

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N2 - Background Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP-101, is in clinical development for treatment of gastroparesis. This double-blind, randomized, placebo-controlled study evaluated the safety and efficacy of multiple TZP-101 doses in patients with moderate to severe symptomatic diabetic gastroparesis. Methods Patients were admitted to the hospital and adaptively randomized to receive a single 30-min intravenous infusion of 20, 40, 80, 160, 320, or 600 μg kg-1 TZP-101, (n = 57) or placebo, (n = 19) for four consecutive days. Symptoms were evaluated daily with the patient-rated Gastroparesis Cardinal Symptom Index (GCSI) and Gastroparesis Symptom Assessment (GSA). Clinicians rated gastroparesis symptoms on treatment day 4. Key Results The 80 μg kg-1 dose was identified as the most effective dose. On day 4, there was statistically significant improvement compared with placebo in the severity of GCSI Loss of Appetite and Vomiting scores for that dose group (P = 0.034 and P = 0.006). In addition, at the 80 μg kg-1 dose, the proportion of patients with at least 50% improvement in vomiting score was significantly different (P = 0.019) compared with placebo. Meal-related GSA scores for Postprandial fullness were significantly improved in the 80 μg kg-1 TZP-101 group compared with placebo (P = 0.012). Clinicians rated the 80 μg kg-1 group better improved than placebo for overall symptom assessment (P = 0.047). Safety profiles were similar in the placebo and TZP-101 groups and all doses were well-tolerated. Conclusions & Inferences TZP-101 appears to be safe, well-tolerated, and effective at acutely addressing several gastroparesis symptoms.

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KW - gastroparesis management

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