Division of Pediatric Pulmonology, State University of New York at Buffalo, Women and Children's Hospital of Buffalo, Buffalo, NY 14222, USA.
J Cyst Fibros. 2011 Dec;10(6):443-52. doi: 10.1016/j.jcf.2011.07.001. Epub 2011 Aug 9.
Most cystic fibrosis (CF) patients have exocrine pancreatic insufficiency (EPI) and need supplementation with pancreatic enzyme replacement therapy (PERT). Liprotamase, a novel non-porcine PERT containing highly purified biotechnology-derived lipase, protease, and amylase, has successfully undergone initial efficacy and safety testing.
In this international phase III parallel-group, randomized-withdrawal, double-blind placebo-controlled trial, CF patients with EPI 7 years and older, including nutritionally and functionally compromised individuals, underwent baseline testing for coefficients of fat and nitrogen absorption (CFA and CNA) and stool weight and frequency while off PERT. After an open-label treatment period with liprotamase, subjects were randomized 1:1 to one liprotamase or placebo capsule taken with 3 meals and 2 snacks per day. The dose was fixed and increases were not allowed. The same measurements were obtained again after treatment with double-blind study drug or placebo.
138 subjects were randomized. The adjusted least squares mean (LSM) difference between the treatment and placebo groups for change in CFA was 15.1% (p=0.001) for the subgroup with baseline CFA <40%, 8.6% (p=0.006) for subjects with baseline CFA ≥40%, and 10.6% (p<0.001) for the overall intent-to-treat population. Similar results were seen for change in CNA. Stool weight was significantly decreased although not stool frequency. Liprotamase was well tolerated with no safety concerns identified.
In a CF patient population reflective of that encountered in clinical practice, this trial demonstrated that liprotamase at a fixed dose of one capsule per meal or snack (5 capsules per day) was well tolerated and significantly increased fat absorption as measured by improvement in CFA, significantly increased protein absorption as measured by improvement in CNA, and significantly decreased stool weight.
大多数囊性纤维化 (CF) 患者存在外分泌胰腺功能不全 (EPI)，需要补充胰酶替代疗法 (PERT)。Liprotamase 是一种新型的非猪源 PERT，含有高度纯化的生物技术衍生的脂肪酶、蛋白酶和淀粉酶，已成功完成初步的疗效和安全性测试。
在这项国际 III 期平行组、随机撤药、双盲安慰剂对照试验中，年龄在 7 岁及以上的 EPI CF 患者，包括营养和功能受损的个体，在停止 PERT 治疗时进行脂肪和氮吸收系数 (CFA 和 CNA)以及粪便重量和频率的基线测试。在接受 Liprotamase 开放标签治疗期后，受试者以 1:1 的比例随机分为 Liprotamase 或安慰剂胶囊，每日随三餐和两餐点服用。剂量固定，不允许增加。在接受双盲研究药物或安慰剂治疗后再次获得相同的测量值。
共有 138 名受试者被随机分配。在基线 CFA<40%的亚组中，治疗组与安慰剂组的 CFA 变化的调整后最小二乘均值 (LSM) 差异为 15.1%（p=0.001），在基线 CFA≥40%的受试者中为 8.6%（p=0.006），在总体意向治疗人群中为 10.6%（p<0.001）。CNA 变化也有类似结果。尽管粪便频率没有变化，但粪便重量显著减少。Liprotamase 耐受性良好，未发现安全性问题。
在反映临床实践中遇到的 CF 患者人群的试验中，该试验表明，Liprotamase 固定剂量为每餐或餐点一粒胶囊（每天 5 粒胶囊）耐受性良好，可显著改善 CFA 以提高脂肪吸收，显著改善 CNA 以提高蛋白质吸收，并显著减少粪便重量。
