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



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.



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.



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.



ClinicalTrials.gov: NCT01710644.
Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address: James.Heubi@cchmc.org.
James E
JE
Heubi
Nemours Children's Clinic, Jacksonville, FL.
David
D
Schaeffer
Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA.
Richard C
RC
Ahrens
University of Kansas School of Medicine-Wichita/Via Christi Research, Wichita, KS.
Natalie
N
Sollo
Rainbow Babies and Children's Hospital, Cleveland, OH.
Steven
S
Strausbaugh
Penn State Milton S. Hershey Medical Center, Hershey, PA.
Gavin
G
Graff
The University of Texas Southwestern Medical Center, Dallas, TX.
Raksha
R
Jain
Nordmark Arzneimittel GmbH & Co. KG, Uetersen, Germany.
Stephan
S
Witte
Nordmark Arzneimittel GmbH & Co. KG, Uetersen, Germany.
Kristin
K
Forssmann
D000293:Adolescent; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000150:complications; D004311:Double-Blind Method; D010188:Exocrine Pancreatic Insufficiency / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D008049:Lipase / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
C081378:solysime; D008049:Lipase
clinical trial; cystic fibrosis; exocrine pancreatic insufficiency; pancreatic enzyme-replacement therapy