Gastroenterology Department, CHU Bordeaux, Saint André Hospital, and Université Victor Segalen Bordeaux 2, Bordeaux, France.
Aliment Pharmacol Ther. 2011 Apr;33(8):911-21. doi: 10.1111/j.1365-2036.2011.04596.x. Epub 2011 Feb 14.
ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro-oesophageal reflux events and oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD) and healthy subjects.
To evaluate the effects of ADX10059 monotherapy for 2 weeks on symptom control in patients with GERD.
This was a double-blind, placebo-controlled, multi-centre trial in GERD patients who were responders to proton pump inhibitors (PPIs). Following PPIs withdrawal, a 2-week baseline washout period was followed by 2-week treatment with either ADX10059 120 mg or placebo b.d. The primary clinical efficacy endpoint was the number of GERD symptom-free days in treatment week 2 compared with the last 7 days of baseline. The effect on reflux events using 24-h impedance-pH monitoring was also determined in a subset of 24 patients.
The full analysis set comprised 103 patients ADX10059 (N= 50), Placebo (N=53). In treatment week 2, ADX10059 significantly increased GERD symptom-free days (P=0.045) and heartburn-free days (P=0.037), reduced antacid use (P=0.017), improved total symptom score (P=0.048) including subscale heartburn/regurgitation (P=0.007) and sleep disturbance because of GERD (P= 0.022). ADX10059 significantly reduced total (P=0.034) and acidic reflux events (P=0.003). ADX10059 was well tolerated. Most common adverse events for ADX10059 were mild to moderate dizziness 16% and vertigo 12% (placebo 4% and 2%).
Inhibition of mGluR5 with ADX10059 monotherapy reduces reflux events and improves symptoms in GERD patients. This mechanism has promise for the management of GERD.
ADX10059 是一种代谢型谷氨酸受体 5（mGluR5）负变构调节剂，已被证明可减少胃食管反流病（GERD）和健康受试者的胃食管反流事件和食管酸暴露。
评估 ADX10059 单药治疗 2 周对 GERD 患者症状控制的影响。
这是一项在对质子泵抑制剂（PPIs）有反应的 GERD 患者中进行的双盲、安慰剂对照、多中心试验。在停用 PPI 后，进行为期 2 周的洗脱期，随后进行为期 2 周的 ADX10059 120mg 或安慰剂 bid 治疗。主要临床疗效终点是治疗第 2 周与基线最后 7 天相比 GERD 无症状天数。通过 24 小时阻抗-pH 监测还确定了 24 例患者亚组的反流事件的影响。
全分析集包括 103 例 ADX10059 患者（N=50）、安慰剂患者（N=53）。在治疗第 2 周，ADX10059 显著增加 GERD 无症状天数（P=0.045）和无烧心天数（P=0.037），减少抗酸剂使用（P=0.017），改善总症状评分（P=0.048），包括烧心/反流亚量表（P=0.007）和 GERD 引起的睡眠障碍（P=0.022）。ADX10059 显著减少总反流事件（P=0.034）和酸性反流事件（P=0.003）。ADX10059 耐受性良好。ADX10059 最常见的不良反应是轻度至中度头晕 16%和眩晕 12%（安慰剂 4%和 2%）。
用 ADX10059 单药抑制 mGluR5 可减少 GERD 患者的反流事件并改善症状。这种机制有望用于 GERD 的治疗。
