Supplementary Material for: A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme Langman C.B. Grujic D. Pease R.M. Easter L. Nezzer J. Margolin A. Brettman L. 10.6084/m9.figshare.3593286.v1 https://karger.figshare.com/articles/dataset/Supplementary_Material_for_A_Double-Blind_Placebo_Controlled_Randomized_Phase_1_Cross-Over_Study_with_ALLN-177_an_Orally_Administered_Oxalate_Degrading_Enzyme/3593286 <p><b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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). <b><i>Conclusions:</i></b> 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.</p> 2016-08-17 06:26:01 ALLN-177 Oral enzyme therapy Kidney stones Oxalate Oxalate nephropathy Secondary hyperoxaluria Urinary oxalate reduction Chronic kidney disease