title: A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme.
abstract: Hyperoxaluria may result from increased endogenous production or overabsorption of dietary oxalate in the gastrointestinal tract leading to nephrolithiasis and, in some, to oxalate nephropathy and chronic kidney disease. ALLN-177 is an oral formulation of a recombinant, oxalate specific, microbial enzyme oxalate decarboxylase intended to treat secondary hyperoxaluria by degrading dietary oxalate in the gastrointestinal tract, thereby reducing its absorption and subsequent excretion in the urine.
  
  
  
  This double-blind, placebo controlled, randomized, cross-over, phase 1 study of ALLN-177 evaluated the tolerability of ALLN-177 and its effect on urinary oxalate excretion in 30 healthy volunteers with hyperoxaluria induced by ingestion of a high oxalate, low calcium (HOLC) diet. The primary end point was the difference in the mean 24-hour urinary oxalate excretion during the ALLN-177 treatment period compared with the placebo treatment period.
  
  
  
  The daily urinary oxalate excretion increased in the study population from 27.2 ± 9.5 mg/day during screening to 80.8 ± 24.1 mg/day (mean ± SD) on the HOLC diet before introducing ALLN-177 or placebo therapy for 7 days. Compared to placebo, ALLN-177 treatment reduced urinary oxalate by 11.6 ± 2.7 mg/day, p = 0.0002 (least squares mean ± SD).
  
  
  
  In healthy volunteers, with diet-induced hyperoxaluria treatment with ALLN-177, when compared to placebo, significantly reduced urinary oxalate excretion by degrading dietary oxalate in the gastrointestinal tract and thereby reducing its absorption. ALLN-177 may represent a new approach for managing secondary hyperoxaluria and its complications.
authors.affiliation: Division of Kidney Diseases, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, and Lurie Children's Hospital of Chicago, Chicago, Ill., USA.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Langman
authors.forename: Danica
authors.initials: D
authors.lastname: Grujic
authors.forename: Rita M
authors.initials: RM
authors.lastname: Pease
authors.forename: Linda
authors.initials: L
authors.lastname: Easter
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nezzer
authors.forename: Alexey
authors.initials: A
authors.lastname: Margolin
authors.forename: Lee
authors.initials: L
authors.lastname: Brettman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001412:Bacillus subtilis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002262:Carboxy-Lyases / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004032:Diet / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D065569:Gastrointestinal Absorption / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D006959:Hyperoxaluria / Q000139:chemically induced / Q000188:drug therapy* / Q000652:urine; D007669:Kidney Calculi / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010070:Oxalates / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D065667:Renal Elimination
chemical_list: D001426:Bacterial Proteins; D010070:Oxalates; D011994:Recombinant Proteins; D002262:Carboxy-Lyases; C021915:oxalate decarboxylase