Safety and preliminary clinical activity of a novel pancreatic enzyme preparation in pancreatic insufficient cystic fibrosis patients.
OBJECTIVE
Currently available pancreatic enzyme products are crude porcine products with few data available regarding their efficacy, safety, and manufacture. We conducted a phase 1 study of a novel pancreatic enzyme product, TheraCLEC-Total (TCT), a proprietary formulation of microbial-derived lipase, protease, and amylase, to determine its safety and preliminary efficacy in cystic fibrosis.


METHODS
We conducted an open-label, dose-ranging study in 23 subjects diagnosed with pancreatic insufficiency with cystic fibrosis. The subjects received TCT containing lipase dose of 100, 500, 1000, 2500, or 5000 USP U/kg per meal with each meal or snack for 3 days. The clinical and laboratory parameters and adverse events (AEs) were monitored.


RESULTS
There were no serious AEs. Most AEs were mild, although gastrointestinal complaints were common. TCT increased the coefficient of fat and nitrogen absorption in all groups except in the low-dose group. At the other dosing levels, the mean coefficient of fat and nitrogen absorption increases were 19.1% +/- 24.9% and 17.8% +/- 13.6%, respectively, whereas the mean stool weight decreased by 517 +/- 362 g.


CONCLUSIONS
TCT was well tolerated in this short-term exposure study. The preliminary efficacy data demonstrate lipase and protease activity with little difference seen with lipase doses greater than 500 USP U/kg per meal. These data support a larger randomized phase 2 trial.
Borowitz
Drucy
D
CF Therapeutics Development Network, Seattle, Wash, USA. dborowitz@upa.chob.edu
Goss
Christopher H
CH
Stevens
Christopher
C
Hayes
Denise
D
Newman
Laurie
L
O'Rourke
Anna
A
Konstan
Michael W
MW
Wagener
Jeffrey
J
Moss
Richard
R
Hendeles
Leslie
L
Orenstein
David
D
Ahrens
Richard
R
Oermann
Christopher M
CM
Aitken
Moira L
ML
Mahl
Thomas C
TC
Young
K Randall
KR
Dunitz
Jordan
J
Murray
Frederick T
FT
D000293:Adolescent; D000328:Adult; D000681:Amylases / Q000008:administration & dosage* / Q000009:adverse effects; D003550:Cystic Fibrosis / Q000150:complications*; D010188:Exocrine Pancreatic Insufficiency / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008049:Lipase / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000008:administration & dosage*
D008049:Lipase; D000681:Amylases; D010447:Peptide Hydrolases; D009584:Nitrogen