Division of Pediatric Pulmonology, Women and Children's Hospital of Buffalo, State University of New York at Buffalo, NY 14222, USA.
J Pediatr Gastroenterol Nutr. 2012 Feb;54(2):248-57. doi: 10.1097/MPG.0b013e31823315d1.
Patients with cystic fibrosis (CF) who have exocrine pancreatic insufficiency (EPI) require treatment with pancreatic enzyme replacement therapy (PERT) to maintain adequate nutrition and age-appropriate growth and weight gain. Liprotamase, a nonporcine, highly purified biotechnology-derived PERT, has demonstrated significant efficacy in fat and protein malabsorption in patients with EPI compared to placebo. This study of liprotamase is the first ever long-term trial of a PERT to evaluate safety and nutritional parameters.
This phase III 12-month open-label trial assessed the safety, tolerability, and long-term nutritional effects of liprotamase treatment in patients with CF and EPI 7 years and older. All of the patients were required to discontinue their long-term use of porcine PERTs at the time of enrollment. Dosing started at 1 capsule of liprotamase (32,500 US Pharmacopoeia (USP) units crystallized cross-linked lipase, 25,000 USP units crystallized protease, and 3,750 USP units amorphous amylase) per meal or snack; dose could be increased based on protocol-defined parameters.
A total of 215 subjects were enrolled and 214 received at least 1 dose of liprotamase (mean 5.5 capsules per day). During the study period, height, weight, and body mass index z scores and lung function as measured by forced expiratory volume in 1 second were stable. There were no clinically meaningful changes in laboratory tests, including levels of fat-soluble vitamins. Liprotamase was well tolerated without any significant safety concerns. Adverse events, primarily gastrointestinal, led to treatment discontinuation for 36 subjects (16.8%), most within the first 3 months.
Treatment with a mean of 5.5 capsules of liprotamase per day, during meals and snacks, for up to 12 months was safe, well tolerated, and associated with age-appropriate growth and weight gain or weight maintenance in subjects with CF-related EPI.
患有外分泌胰腺功能不全 (EPI) 的囊性纤维化 (CF) 患者需要接受胰酶替代疗法 (PERT) 治疗，以维持充足的营养和适合年龄的生长和体重增加。与安慰剂相比，非猪源、高度纯化的生物技术衍生 PERT 制剂 liprotamase 在 EPI 患者的脂肪和蛋白质吸收不良方面显示出显著疗效。这项 liprotamase 的研究是首次对 PERT 进行的长期试验，以评估安全性和营养参数。
这项为期 12 个月的 III 期开放标签试验评估了 liprotamase 在 7 岁及以上 CF 和 EPI 患者中的安全性、耐受性和长期营养作用。所有患者在入组时均需停止长期使用猪源 PERT。起始剂量为每餐或零食服用 1 粒 liprotamase（32500USP 结晶交联脂肪酶单位、25000USP 结晶蛋白酶单位和 3750USP 无定形淀粉酶单位）；根据方案规定的参数，可以增加剂量。
共有 215 名受试者入组，214 名受试者至少接受了 1 次 liprotamase 治疗（平均每天 5.5 粒）。在研究期间，身高、体重和体重指数 z 评分以及通过 1 秒用力呼气量测量的肺功能保持稳定。实验室检查包括脂溶性维生素水平在内，均无临床意义的变化。liprotamase 耐受性良好，无明显安全性问题。不良事件主要为胃肠道，导致 36 名受试者（16.8%）停药，大多数发生在最初 3 个月内。
在 12 个月的时间里，每天平均服用 5.5 粒 liprotamase，随餐和零食服用，安全且耐受良好，与 CF 相关 EPI 患者的年龄相符的生长和体重增加或维持。
