Pharmacological Class:
Antidiarrheal.
Active Ingredient(s):
Crofelemer 125mg; delayed-release tablets; enteric-coated.
Company
Salix Pharmaceuticals, Inc.
Indication(s):
Symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy.
Pharmacology:
Crofelemer is an inhibitor of both cyclic adenosine monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel and the calcium-activated chloride ion channels (CaCC) at the luminal membrane of enterocytes. CFTR chloride ion channel and CaCC regulate chloride ion and fluid secretion by intestinal epithelial cells. Crofelemer blocks chloride ion secretion and the accompanying high volume water loss in diarrhea, normalizing the flow of chloride ions and water in the GI tract.
Clinical Trials:
The efficacy of crofelemer was evaluated in a randomized, double-blind, placebo-controlled (one month) and placebo-free (five month), multi-center study. The study enrolled 374 HIV-positive patients on stable antiretroviral therapy (ART) with a history of diarrhea for one month or more.
The study had a two-stage adaptive design. In both stages patients received placebo for 10 days (screening period) followed by randomization to crofelemer or placebo for 31 days of treatment (double-blind period). Only patients with one or more watery bowel movements per day on at least 5 of the 7 days in the screening period were randomized to the double-blind period. In the first stage, patients were randomized 1:1:1:1 to one of the three crofelemer dose regimens (125mg, 250mg, or 500mg twice daily.) or placebo. In the second stage, patients were randomized 1:1 to crofelemer 125mg twice daily or placebo. The efficacy analysis was based on results from the double-blind portion of both stages. Each study stage also had a five month period (placebo-free period) that followed the double-blind period. Patients treated with crofelemer continued the same dose in the placebo-free period. In the first stage, patients that received placebo were re-randomized 1:1:1 to one of the three crofelemer dose regimens (125mg, 250mg, or 500mg twice daily) in the placebo-free period. In the second stage, patients that received placebo were treated with crofelemer 125mg twice daily in the placebo-free period.
In the double-blind period of the study, 136 patients received crofelemer 125mg twice daily, 54 patients received 250mg twice daily, 47 patients received 500mg twice daily, and 138 patients received placebo. The percentages of patients that completed the double-blind period were 92%, 100%, 85%, and 94% in the 125mg, 250mg, 500mg, and placebo arms, respectively.
The primary efficacy endpoint was the proportion of patients with a clinical response, defined as ≤2 watery bowel movements per week during at least 2 of the 4 weeks of the placebo-controlled phase. Patients who received concomitant antidiarrheal medication or opiates were counted as clinical non-responders. A significantly larger proportion of patients in the crofelemer 125mg twice daily group experienced clinical response compare with patients in the placebo group (17.6% vs. 8%, 1-sided P<0.01).
In the randomized clinical study, examination of duration of diarrhea, baseline number of daily watery bowel movements, use of protease inhibitors, CD4 cell count and age subgroups did not identify differences in the consistency of the crofelemer treatment effect among these subgroups.
Of the 24 clinical responders to crofelemer (125mg twice daily), 22 entered the placebo-free period; 16 were responding at the end of month 3, and 14 were responding at the end of month 5.
Legal Classification:
Rx
Adults:
Swallow whole. One tab twice daily.
Children:
<18 years: not established.
Warnings/Precautions:
Rule out infectious etiologies of diarrhea before starting. Pregnancy (Category C). Nursing mothers: not recommended.
Adverse Reaction(s)
Upper respiratory tract infection, bronchitis, cough, flatulence, increased bilirubin.
How Supplied:
Tabs—60
LAST UPDATED:
8/23/2013
活性成分（S）：
Crofelemer的次125mg缓释片，肠溶。
公司
Salix制药公司
指示（S）：
非感染性腹泻，在与艾滋病毒/艾滋病的抗逆转录病毒治疗的成年患者的症状缓解。
药理作用：
Crofelemer的是两个环磷酸腺苷（cAMP）的刺激囊性纤维化跨膜传导调节器（CFTR）氯离子通道，钙激活的氯离子通道（CACC）在肠上皮细胞的管腔膜的抑制剂。 CFTR氯离子通道了CACC调节氯离子和肠上皮细胞的分泌液。 Crofelemer的块的氯离子分泌和腹泻随附的高体积的水损失，归一化的氯离子和水在胃肠道中的流动。
临床试验：
在随机，双盲，安慰剂对照（一个月）和安慰剂（5个月），多中心研究评估Crofelemer的疗效。该研究纳入了374名HIV阳性患者一个月或更稳定的抗逆转录病毒疗法（ART）的历史腹泻。
研究了自适应两阶段设计。在这两个阶段中，患者接受安慰剂筛选期10天（由随机Crofelemer的或安慰剂），其次为31天的治疗（双盲时期）。只有患者与一个或多个水汪汪每天排便在筛选期间的7天至少5随机双盲期限。在第一阶段中，患者被随机1:1:1:1三个Crofelemer的剂量（125毫克，250毫克，500毫克，每日两次）或安慰剂。在第二阶段，患者随机1:1 Crofelemer的次125mg，每日两次或安慰剂。疗效分析是基于两个阶段双盲部分结果。每个研究阶段，也有5个月期间（安慰剂期）之后的双盲期间。 Crofelemer的治疗的患者继续相同剂量的安慰剂无霜期。在第一阶段，接受安慰剂的患者重新随机1:1:1三个Crofelemer的剂量（125毫克，250毫克，500毫克，每日两次）安慰剂期间。在第二阶段，患者接受安慰剂治疗与Crofelemer的125毫克，每日两次安慰剂无霜期。
在双盲的研究期间，有136名患者接受Crofelemer的次125mg，每日两次，54名患者接受250毫克，每天两次，47名患者接受500毫克，每日两次，138例接受安慰剂。完成的双盲期间的患者的百分比分别为92％，100％，85％，94％，125毫克，250毫克，500毫克和安慰剂组，分别。
主要疗效终点是患者的临床反应，在至少2个4周的安慰剂对照阶段定义为≤2水汪汪的每周排便的比例。患者同时接受止泻药或鸦片算作临床非应答。 à显着比例较大的患者Crofelemer的次125mg，每日两次经历临床反应与安慰剂组患者（17.6％与8％，1双侧P <0.01）。
随机临床研究，检查腹泻持续时间，每天的水样排便的基线数，使用蛋白酶抑制剂，CD4细胞计数和各种亚组未识别的一致性，在这些子组中的Crofelemer的治疗效果的差异。
24个临床Crofelemer的应答（次125mg，每日两次），22进入安慰剂免费的时期;响应16月底的3个月，和14响应在5月结束。
法律分类：
接收
成人：
整片吞服。一个选项卡，每日两次。
儿童：
<18岁：不成立的。
警告/注意事项：
开始之前，排除传染性腹泻的病因。怀孕（C类）。哺乳母亲：不推荐。
不良反应（S）
上呼吸道感染，支气管炎，咳嗽，胃肠胀气，胆红素增加。
如何提供：
标签-60
最后更新：
2013年8月23日