Tack J, Rotondo A, Meulemans A, Thielemans L, Cools M
TARGID, University of Leuven, Leuven, Belgium.
Shire-Movetis NV, Turnhout, Belgium.
Neurogastroenterol Motil. 2016 Apr;28(4):487-97. doi: 10.1111/nmo.12736.
Gastroparesis is a chronic gastric disorder characterized by delayed gastric emptying without mechanical obstruction, and clinical symptoms as postprandial fullness, early satiety, bloating, nausea, vomiting, and abdominal pain. Prokinetic agents are used for the treatment of gastroparesis. Revexepride, a 5-hydroxytryptamine (serotonin) receptor (5-HT4 R) agonist, could be a good candidate drug for the gastroparesis treatment.
In the current phase II, exploratory, double-blind, randomized, stratified, placebo-controlled, repeated dose trial (EudraCT number 2007-004997-23), the efficacy on gastrointestinal symptoms and gastric emptying rate, safety, and pharmacokinetic profile of three oral doses of revexepride (0.02, 0.1, and 0.5 mg administered orally t.i.d. for 4 weeks) was evaluated in trial participants (diabetic and non-diabetic) with upper gastrointestinal tract symptoms suggestive for gastroparesis.
Eighty participants, enrolled in four parallel treatment groups, were asked to score their symptom diary data, gastroparesis cardinal symptom index (GCSI), patient assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM), quality of life questionnaires, and meal-related symptom score. Gastric emptying rate was evaluated by (13) C-octanoic acid breath test.
The severity of the symptoms assessed by means of GCSI and PAGI-SYM decreased at Week 2 and decreased further at Week 4 in all treatment groups including placebo, with similar trends in all treatment groups. Quality of life improved in all treatment groups after 4 weeks of treatment. No differences on gastric emptying rate were shown between any of the active treatment groups and placebo. Revexepride was generally safe and well-tolerated.
CONCLUSIONS & INFERENCES: Four weeks of revexepride treatment did not improve symptoms or gastric emptying over placebo in patients with symptoms suggestive of gastroparesis.
胃轻瘫是一种慢性胃部疾病，其特征为胃排空延迟且无机械性梗阻，并伴有餐后饱胀、早饱、腹胀、恶心、呕吐及腹痛等临床症状。促动力药用于治疗胃轻瘫。瑞伐必利是一种5-羟色胺（血清素）受体（5-HT4R）激动剂，可能是治疗胃轻瘫的一种理想候选药物。
在当前的II期探索性双盲随机分层安慰剂对照重复剂量试验（欧盟临床试验编号2007-004997-23）中，对80名有提示胃轻瘫的上消化道症状的试验参与者（糖尿病患者和非糖尿病患者）口服三种剂量（0.02、0.1和0.5毫克，每日三次，共4周）的瑞伐必利后的胃肠道症状疗效、胃排空率、安全性及药代动力学特征进行了评估。
80名参与者被纳入四个平行治疗组，要求他们对症状日记数据、胃轻瘫主要症状指数（GCSI）、上消化道疾病患者评估-症状严重程度指数（PAGI-SYM）、生活质量问卷及进餐相关症状评分进行打分。通过¹³C-辛酸呼气试验评估胃排空率。
在包括安慰剂组在内的所有治疗组中，通过GCSI和PAGI-SYM评估的症状严重程度在第2周时降低，在第4周时进一步降低，所有治疗组趋势相似。治疗4周后，所有治疗组的生活质量均有所改善。任何活性治疗组与安慰剂组之间在胃排空率方面均未显示出差异。瑞伐必利总体安全且耐受性良好。
对于有胃轻瘫症状的患者，与安慰剂相比，四周的瑞伐必利治疗并未改善症状或胃排空情况。
