Aarhus University, Aarhus, Denmark.
Neurogastroenterol Motil. 2010 Oct;22(10):1069-e281. doi: 10.1111/j.1365-2982.2010.01519.x. Epub 2010 Jun 28.
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.
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.
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.
胃轻瘫是一种异常胃动力的慢性疾病，在糖尿病患者中很常见。一种合成的、选择性的生长激素释放肽受体激动剂 TZP-101，正在开发用于治疗胃轻瘫。这项双盲、随机、安慰剂对照研究评估了多种 TZP-101 剂量在中重度症状性糖尿病性胃轻瘫患者中的安全性和疗效。
患者入院并适应性随机接受单次 30 分钟静脉输注 20、40、80、160、320 或 600μgkg(-1)TZP-101（n=57）或安慰剂（n=19），连续 4 天。每天使用患者自评胃轻瘫 cardinal 症状指数（GCSI）和胃轻瘫症状评估（GSA）评估症状。临床医生在治疗第 4 天评估胃轻瘫症状。
80μgkg(-1)剂量被确定为最有效剂量。与安慰剂相比，该剂量组在第 4 天的 GCSI 食欲不振和呕吐严重程度评分均有统计学意义的改善（P=0.034 和 P=0.006）。此外，在 80μgkg(-1)剂量组，呕吐评分至少改善 50%的患者比例与安慰剂相比差异有统计学意义（P=0.019）。与安慰剂相比，80μgkg(-1)TZP-101 组餐后饱胀的与进餐相关的 GSA 评分显著改善（P=0.012）。临床医生评价 80μgkg(-1)组的整体症状改善优于安慰剂（P=0.047）。安慰剂和 TZP-101 组的安全性特征相似，所有剂量均耐受良好。
TZP-101 似乎安全、耐受良好，能有效迅速缓解多种胃轻瘫症状。
