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

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.

Study Overview

• Status: Completed
• Conditions: Endstage Renal Disease
• Intervention / Treatment: Drug: low-dose sucroferric oxyhydroxide; Drug: high-dose sucroferric oxyhydroxide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Ordensklinikum Linz GmbH Elisabethinen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Prim. Priv. Doz. Dr. Daniel Cejka
• Collaborators: Vifor Fresenius Medical Care Renal Pharma
• Investigators: Principal Investigator: Daniel Cejka, Dr., Sponsor/PI

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2017
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): May 10, 2019

Study Registration Dates

• First Submitted: December 22, 2016
• First Submitted That Met QC Criteria: January 3, 2017
• First Posted (Estimate): January 4, 2017

Study Record Updates

• Last Update Posted (Actual): July 22, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Hematinics; Ferric Compounds
• Other Study ID Numbers: PA21-T50-CKD5D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No