Abstract
Purpose: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. Methods: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. Results: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI − 23.71, − 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (− 2.8; 95% CI − 4.9, − 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. Conclusion: ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria. Trial registration: Clinicaltrials.gov NCT02289755.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 601-608 |
| Number of pages | 8 |
| Journal | International urology and nephrology |
| Volume | 51 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2019 |
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Keywords
- Bariatric surgery
- Enteric hyperoxaluria
- Nephrolithiasis
- Oxalate
ASJC Scopus subject areas
- Nephrology
- Urology
Cite this
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ALLN-177, oral enzyme therapy for hyperoxaluria. / Lingeman, James E.; Pareek, Gyan; Easter, Linda; Pease, Rita; Grujic, Danica; Brettman, Lee; Langman, Craig B.
In: International urology and nephrology, Vol. 51, No. 4, 01.04.2019, p. 601-608.Research output: Contribution to journal › Article
TY - JOUR
T1 - ALLN-177, oral enzyme therapy for hyperoxaluria
AU - Lingeman, James E.
AU - Pareek, Gyan
AU - Easter, Linda
AU - Pease, Rita
AU - Grujic, Danica
AU - Brettman, Lee
AU - Langman, Craig B.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Purpose: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. Methods: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. Results: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI − 23.71, − 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (− 2.8; 95% CI − 4.9, − 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. Conclusion: ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria. Trial registration: Clinicaltrials.gov NCT02289755.
AB - Purpose: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. Methods: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. Results: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI − 23.71, − 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (− 2.8; 95% CI − 4.9, − 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. Conclusion: ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria. Trial registration: Clinicaltrials.gov NCT02289755.
KW - Bariatric surgery
KW - Enteric hyperoxaluria
KW - Nephrolithiasis
KW - Oxalate
UR - http://www.scopus.com/inward/record.url?scp=85061826398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061826398&partnerID=8YFLogxK
U2 - 10.1007/s11255-019-02098-1
DO - 10.1007/s11255-019-02098-1
M3 - Article
C2 - 30783888
AN - SCOPUS:85061826398
VL - 51
SP - 601
EP - 608
JO - International Urology and Nephrology
JF - International Urology and Nephrology
SN - 0301-1623
IS - 4
ER -