TY - JOUR
T1 - Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis
T2 - a randomized, placebo-controlled study
AU - Ejskjaer, N
AU - Dimcevski, G
AU - Wo, J
AU - Hellström, P M
AU - Gormsen, L C
AU - Sarosiek, I
AU - Søfteland, E
AU - Nowak, T
AU - Pezzullo, J C
AU - Shaughnessy, L
AU - Kosutic, G
AU - McCallum, R
PY - 2010/10
Y1 - 2010/10
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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Appetite/drug effects
KW - Diabetes Complications/drug therapy
KW - Diabetes Mellitus, Type 1/complications
KW - Diabetes Mellitus, Type 2/complications
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Endpoint Determination
KW - Female
KW - Gastroparesis/drug therapy
KW - Ghrelin/agonists
KW - Humans
KW - Macrocyclic Compounds/adverse effects
KW - Male
KW - Middle Aged
KW - Satiety Response/drug effects
KW - Surveys and Questionnaires
KW - Vomiting/epidemiology
KW - Young Adult
U2 - 10.1111/j.1365-2982.2010.01519.x
DO - 10.1111/j.1365-2982.2010.01519.x
M3 - Journal article
C2 - 20524987
SN - 1365-2982
VL - 22
SP - 1069-e281
JO - Neurogastroenterology and Motility Online
JF - Neurogastroenterology and Motility Online
IS - 10
ER -