Safety and Efficacy of a Novel Microbial Lipase in Patients with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis: A Randomized Controlled Clinical Trial

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• 作者：James E. Heubi ; MD¹ ; ^{James.Heubi@cchmc.org" class="auth_mail" title="E-mail the corresponding author} ; David Schaeffer ; MD² ; Richard C. Ahrens ; MD³ ; Natalie Sollo ; MD⁴ ; Steven Strausbaugh ; MD⁵ ; Gavin Graff ; MD⁶ ; Raksha Jain ; MD⁷ ; Stephan Witte ; PhD⁸ ; Kristin Forssmann ; MD⁸
• 关键词：clinical trial ; cystic fibrosis ; exocrine pancreatic insufficiency ; pancreatic enzyme-replacement therapy
• 刊名：The Journal of Pediatrics
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：176
• 期：Complete
• 页码：156-161.e1
• 全文大小：412 K

文摘

To evaluate the safety and efficacy of a novel microbial lipase (NM-BL) in a liquid formulation for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF) in a phase IIa proof-of-concept study.

Study design

We conducted a double-blind, randomized, placebo controlled crossover study in patients with cystic fibrosis and exocrine pancreatic insufficiency. Adolescent and adult patients with CF were randomized to receive NM-BL or placebo for 1 week as replacement for their usual pancreatic enzyme formulation. They were subsequently crossed-over to the alternate study treatment. The coefficient of fat absorption was evaluated as the primary endpoint. Symptoms and adverse events were evaluated as secondary endpoints.

Results

A total of 35 patients were randomized into the study and 22 patients completed both treatment periods. During treatment with NM-BL, the coefficient of fat absorption was significantly greater (72.7%) compared with placebo (53.8%) with a difference between groups of 18.8% (P < .001). Subjective assessment of stool fat and stool consistency also improved under treatment with NM-BL. Adverse events were mostly gastrointestinal in nature and were more common in the group receiving NM-BL.

Conclusions

Currently available pancreatic enzyme products are limited because of the lack of liquid formulations and being largely porcine based. The novel microbial lipase NM-BL was safe and effective in this short term trial. The trial provided clinical proof-of-concept for this novel microbial lipase as a treatment for EPI in CF. A larger phase 2 dose ranging trial is warranted.

Trial Registration

ClinicalTrials.gov: NCT01710644.