Abstract
Background: 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. Methods: 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. Results: 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). Conclusions: 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.
Original language | English (US) |
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Pages (from-to) | 150-158 |
Number of pages | 9 |
Journal | American Journal of Nephrology |
Volume | 44 |
Issue number | 2 |
DOIs | |
State | Published - Sep 1 2016 |
Keywords
- ALLN-177
- Chronic kidney disease
- Kidney stones
- Oral enzyme therapy
- Oxalate
- Oxalate nephropathy
- Secondary hyperoxaluria
- Urinary oxalate reduction
ASJC Scopus subject areas
- Nephrology
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Dive into the research topics of 'A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme'. Together they form a unique fingerprint.Datasets
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PowerPoint Slides for: A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme
Langman, C. (Creator), Grujic, D. (Creator), Pease, R. M. (Creator), Easter, L. (Creator), Nezzer, J. (Creator), Margolin, A. (Creator) & Brettman, L. (Creator), Karger Publishers, 2016
DOI: 10.6084/m9.figshare.3635727.v3, https://karger.figshare.com/articles/dataset/PowerPoint_Slides_for_A_Double-Blind_Placebo_Controlled_Randomized_Phase_1_Cross-Over_Study_with_ALLN-177_an_Orally_Administered_Oxalate_Degrading_Enzyme/3635727/3
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PowerPoint Slides for: A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme
Langman, C. (Creator), Grujic, D. (Creator), Pease, R. M. (Creator), Easter, L. (Creator), Nezzer, J. (Creator), Margolin, A. (Creator) & Brettman, L. (Creator), Karger Publishers, 2016
DOI: 10.6084/m9.figshare.3635727.v1, https://karger.figshare.com/articles/dataset/PowerPoint_Slides_for_A_Double-Blind_Placebo_Controlled_Randomized_Phase_1_Cross-Over_Study_with_ALLN-177_an_Orally_Administered_Oxalate_Degrading_Enzyme/3635727/1
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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. (Creator), Grujic, D. (Creator), Pease, R. M. (Creator), Easter, L. (Creator), Nezzer, J. (Creator), Margolin, A. (Creator) & Brettman, L. (Creator), Karger Publishers, 2016
DOI: 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/3593286/1
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