Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers
ABSTRACT Despite the widespread use of currently available serum phosphate management options, elevated serum phosphate is common in patients with end‐stage kidney disease on dialysis. Characteristics of currently available phosphate binders that lead to poor patient experiences such as large drug v...
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Wiley
2025-01-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70116 |
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| author | Pablo E. Pergola Melanie S. Joy Armando Garsd Steve J. Hasal Atul Khare Guru Reddy Pramod Gupta William F. Finn |
| author_facet | Pablo E. Pergola Melanie S. Joy Armando Garsd Steve J. Hasal Atul Khare Guru Reddy Pramod Gupta William F. Finn |
| author_sort | Pablo E. Pergola |
| collection | DOAJ |
| description | ABSTRACT Despite the widespread use of currently available serum phosphate management options, elevated serum phosphate is common in patients with end‐stage kidney disease on dialysis. Characteristics of currently available phosphate binders that lead to poor patient experiences such as large drug volume size of required daily medication (e.g., many large tablets) and adverse gastrointestinal effects may decrease compliance to labeled dosing instructions, thus decreasing their efficacy. Oxylanthanum carbonate is a new molecule yielding the same phosphate‐binding capacity as lanthanum carbonate, but in a much smaller drug volume and tablet size. It is formulated as small tablets that can be easily swallowed. In a double‐blind dose‐escalation phase 1 study, healthy volunteers (n = 32) were randomly divided into four treatment arms and randomly assigned to receive oxylanthanum carbonate tablets or a placebo over a period of 4 days to evaluate safety, urinary and fecal excretion of phosphorus, and pharmacokinetics. Each treatment arm evaluated a different dose of oxylanthanum carbonate: 500, 1000, 1500, or 2000 mg three times a day (TID). The study drug was well‐tolerated. Oxylanthanum carbonate effectively decreased dietary phosphorus absorption, demonstrated by decreased urinary phosphorus excretion and increased fecal phosphorus excretion. Systemic absorption of oxylanthanum carbonate was minimal, with lanthanum serum concentration values below the level of quantification (0.500 ng/mL) in all subjects receiving 500 mg TID and did not exceed 0.7 ng/mL at other doses. Future studies should evaluate and confirm the ability of oxylanthanum carbonate to reduce pill burden and improve dose administration, patient tolerability, adherence, and treatment outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT01560884 |
| format | Article |
| id | doaj-art-731171a5ad2e454b837872ef3ea82b9e |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj-art-731171a5ad2e454b837872ef3ea82b9e2025-01-24T08:17:46ZengWileyClinical and Translational Science1752-80541752-80622025-01-01181n/an/a10.1111/cts.70116Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy VolunteersPablo E. Pergola0Melanie S. Joy1Armando Garsd2Steve J. Hasal3Atul Khare4Guru Reddy5Pramod Gupta6William F. Finn7Renal Associates, PA San Antonio Texas USASkaggs School of Pharmacy and Pharmaceutical Sciences, School of Medicine, Division of Renal Diseases and Hypertension University of Colorado Aurora Colorado USAStatistical Consultant Unicycive Therapeutics Inc. Los Altos California USAUnicycive Therapeutics Inc. Los Altos California USAUnicycive Therapeutics Inc. Los Altos California USAUnicycive Therapeutics Inc. Los Altos California USAUnicycive Therapeutics Inc. Los Altos California USAUniversity of North Carolina at Chapel Hill Chapel Hill North Carolina USAABSTRACT Despite the widespread use of currently available serum phosphate management options, elevated serum phosphate is common in patients with end‐stage kidney disease on dialysis. Characteristics of currently available phosphate binders that lead to poor patient experiences such as large drug volume size of required daily medication (e.g., many large tablets) and adverse gastrointestinal effects may decrease compliance to labeled dosing instructions, thus decreasing their efficacy. Oxylanthanum carbonate is a new molecule yielding the same phosphate‐binding capacity as lanthanum carbonate, but in a much smaller drug volume and tablet size. It is formulated as small tablets that can be easily swallowed. In a double‐blind dose‐escalation phase 1 study, healthy volunteers (n = 32) were randomly divided into four treatment arms and randomly assigned to receive oxylanthanum carbonate tablets or a placebo over a period of 4 days to evaluate safety, urinary and fecal excretion of phosphorus, and pharmacokinetics. Each treatment arm evaluated a different dose of oxylanthanum carbonate: 500, 1000, 1500, or 2000 mg three times a day (TID). The study drug was well‐tolerated. Oxylanthanum carbonate effectively decreased dietary phosphorus absorption, demonstrated by decreased urinary phosphorus excretion and increased fecal phosphorus excretion. Systemic absorption of oxylanthanum carbonate was minimal, with lanthanum serum concentration values below the level of quantification (0.500 ng/mL) in all subjects receiving 500 mg TID and did not exceed 0.7 ng/mL at other doses. Future studies should evaluate and confirm the ability of oxylanthanum carbonate to reduce pill burden and improve dose administration, patient tolerability, adherence, and treatment outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT01560884https://doi.org/10.1111/cts.70116chronic kidney diseaseend‐stage kidney diseasehyperphosphatemiaoxylanthanum carbonatephosphate binder |
| spellingShingle | Pablo E. Pergola Melanie S. Joy Armando Garsd Steve J. Hasal Atul Khare Guru Reddy Pramod Gupta William F. Finn Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers Clinical and Translational Science chronic kidney disease end‐stage kidney disease hyperphosphatemia oxylanthanum carbonate phosphate binder |
| title | Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers |
| title_full | Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers |
| title_fullStr | Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers |
| title_full_unstemmed | Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers |
| title_short | Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers |
| title_sort | safety and phosphate binding capacity of oxylanthanum carbonate in healthy volunteers |
| topic | chronic kidney disease end‐stage kidney disease hyperphosphatemia oxylanthanum carbonate phosphate binder |
| url | https://doi.org/10.1111/cts.70116 |
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