The Effect of Phosphate Lowering Using Sucroferric Oxyhydroxide (PA21) on Calcification Propensity of Serum

Study Overview
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Brief Summary
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This is a single-center, prospective, open-label, controlled, randomized, cross-over study in 34 prevalent end-stage renal disease patients on chronic hemodialysis treatment with hyperphosphatemia.

Detailed Description
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Patients will be randomized in a 1:1 ratio to either receive low-dose (250mg/d) PA-21 followed by high-dose (2000mg/d) PA-21 (sequence A-B) or to receive high-dose PA21 followed by low-dose PA21 (sequence B-A) with washout-phases in between. An open label design with a sub-therapeutic dose of PA21 as control treatment was chosen because creating a convincing placebo for PA21 is not feasible. The study will start with two study visits on the 2nd and 3rd dialysis session of the week , where dialysis patients are still treated with standard of care to establish baseline values (duration: 0.5 weeks). Next will be an initial run-in wash-out phase, where all phosphate binders taken by the patient as standard of care treatment will be discontinued and no phosphate binders will be introduced. Consequently, there will be a PA21 treatment (high dose/low dose) phase, followed by a wash-out phase, followed by another PA21 treatment (high dose/low dose) phase, followed by a final wash-out phase. Each study phase, including wash-out phases as well as low-dose and high-dose treatment phases will be 14 days of duration. Patients will be followed up to 10.5 weeks after randomization until the last study visit of the final wash-out phase.

Official Title
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The Effect of Phosphate Lowering Using Sucroferric Oxyhydroxide (PA21) on Calcification Propensity of Serum

Conditions
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Endstage Renal Disease

Intervention / Treatment
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* Drug: low-dose sucroferric oxyhydroxide
* Drug: high-dose sucroferric oxyhydroxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prevalent patients (≥ 3 months on dialysis) treated with thrice weekly hemodialysis (HD) or hemodiafiltration (HDF) Hyperphosphatemia (serum phosphate > upper limit of normal within the last 3 months) or current phosphate binder use No use or constant dose of vitamin D and/or calcimimetics for ≥2 weeks Exclusion Criteria: Allergy to sucroferric oxyhydroxide (PA21), to other ingredients of Velphoro or to any iron-medication Current or history of calciphylaxis (calcific uremic arteriolopathy - CUA) parathormone >800 pg/ml Parathyreoidektomie planned or expected Significant GI or hepatic disorders Hypercalcemia (total serum calcium >2.6 mmol/l) at screening Antacids containing aluminum, calcium, magnesium or bicarbonate Oral iron treatments/supplements Pregnant and nursing (lactating) women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: low-dose sucroferric oxyhydroxide<br>Low dose 250 mg sucroferric oxyhydroxide (PA21) per day (1x 250mg tablets/day) for 14 days. | Drug: low-dose sucroferric oxyhydroxide<br>* 250 mg suroferric oxyhydroxide<br>* Other names: Velphoro;|
| Active Comparator: high-dose sucroferric oxyhydroxide<br>Uniform dose 2000 mg of sucroferric oxyhydroxide (PA21) per day (4x 500mg tablets/day) for 14 days | Drug: high-dose sucroferric oxyhydroxide<br>* 2000 mg suroferric oxyhydroxide<br>* Other names: Velphoro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Propensity of serum for calcification - H1 | The primary outcome is change in the mean T50- Test values between different study phases (wash-out/treatment/control). | 10.5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Phosphate | The secondary outcome is the Change of mean Serum Phosphate Levels between different study visits | 10.5 weeks |