Conditions: Hyperphosphatemia
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 55
Healthy volunteers: no

Brief summary:
Transition to Ferric Citrate among Hemodialysis and Peritoneal Dialysis Patients: A Phase 4 "Real World" Experience Study from Kaiser Permanente Southern California

Detailed description:
PROTOCOL SUMMARY

Title: Transition to Ferric Citrate among Hemodialysis and Peritoneal Dialysis Patients: A Phase 4 "Real World" Experience Study from Kaiser Permanente Southern California

Short Title: FeCitrate

Protocol Number: KP FeCitrate

Study Phase: 4

Study Site(s): Los Angeles Kaiser Sunset Medical Center

Number of Subjects: 55

Study Arms: 1

Indication: Hyperphosphatemia in end stage renal disease

Primary Purpose: To evaluate the efficacy of ferric citrate for control of serum phosphorus levels and maintenance of adequate iron stores among dialysis-dependent patients before and after conversion from traditional phosphate binders in a "real world" environment

Overview of Study Design: Prospective non-randomized cohort study of 6-9 months duration (active study period 6 months).

Investigational Product Administration: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.

Study Endpoint: Mean serum phosphorus levels and rate of successful phosphorus control (\<5.5mg/dl) 6 months before and after treatment with ferric citrate

Statistical Methods: Not powered to detect statistical significance

Arms:
arm 1: Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles.

Interventions: intervention 1: Ferric Citrate
Intervention descriptions: intervention 1: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.

Protocol document:
Prot_SAP_000.pdf: 
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PROTOCOL NUMBER:  
FeCitrate 
 
 
TITLE:  
Transition to Ferric Citrate among Hemodialysis and 
Peritoneal Dialysis Patients: 
 
 
STUDY PHASE: 
Phase IV   
 
IND OR IDE#: 
N/A 
 
PRINCIPAL INVESTIGATOR: 
Victoria A. Kumar, M.D. or Hui Xue, M.D. 
 
Nephrology 
LAMC 
 
4700 Sunset Bl 
Los Angeles, CA 90027 
 
CONTACT INFORMATION: 
NCT03079869 
 
 
FUNDED BY: 
Keryx Medical Affairs 
One Marina Park Drive, Tenth Floor 
Boston, MA 02210 
 
STUDY SITES: 
LAMC 
 
 
 
AMENDMENTS/REVISIONS: 
Protocol Version 1.4, dated 26-Jun-2018 
 
  
 
 


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TABLE OF CONTENTS 
 
PROTOCOL AMENDMENT……………………………………………………………………………………………………5-8  
LIST OF ABBREVIATIONS ............................................................................................................. 9 
PROTOCOL SUMMARY ............................................................................................. ……..10..10-11 
1 
INTRODUCTION ................................................................................................................... 12 
1.2  
Investigational Agent ..................................................................................................... 13 
1.3  
Preclinical Data ............................................................................................................... 13 
1.4  
Clinical Data to Date ....................................................................................................... 13 
1.5  
Hypothesis ...................................................................................................................... 13 
2 
OBJECTIVES AND PURPOSE ................................................................................................ 13 
3 STUDY DESIGN ............................................................................................................................ 14 
3.1 
Treatment Arms ............................................................................................................. 15 
3.2   
Study Duration ............................................................................................................... 15 
4 
STUDY PRODUCT INFORMATION ...................................................................................... 15 
4.1 
Description ..................................................................................................................... 15 
4.2  
Acquisition and Accountability ....................................................................................... 15 
4.3  
Formulation, Packaging, and Labeling ........................................................................... 16 
4.4  
Storage and Stability ...................................................................................................... 16 
4.5  
Dosage, Preparation and Administration ....................................................................... 16 
4.6 
Toxicity and Safety Information ..................................................................................... 16 
4.7 
Concomitant Medications/ Treatments ......................................................................... 16 
5 
SELECTION AND WITHDRAWAL OF PATIENTS ............................................................... 17 
5.1 
Inclusion Criteria ............................................................................................................ 17 
5.2 Exclusion Criteria ................................................................................................................. 17 
5.3 
Withdrawal Criteria ........................................................................................................ 17 
6 
STRATIFICATION/ RANDOMIZATION SCHEME ............................................................... 17 
7 
STUDY PRODUCT ADMINISTRATION AND TOXICITY MANAGEMENT PLAN ................ 18 


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7.1  
Administration ................................................................................................................ 18 
7.2 
Criteria for Removal from Treatment ............................................................................ 19 
7.3 
Comorbidities ................................................................................................................. 19 
8 
ASSESSMENT OF EFFICACY AND SAFETY ......................................................................... 19 
8.1 
Toxicity Monitoring ........................................................................................................ 19 
8.2 
Modification of Study Product Administration based on Toxicity ................................. 20 
8.3 
Adverse Events Reporting .............................................................................................. 20 
9 
STUDY SCHEDULE: CLINICAL/ LABORATORY EVALUATIONS ....................................... 23 
9.1  Study Schedule ................................................................................................................... 23 
9.2 
Clinical Evaluations ......................................................................................................... 27 
9.3 
Laboratory Evaluations................................................................................................... 27 
9.4 
Study Calendar ............................................................................................................... 28 
10 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS ..................................... 29 
10.1 Primary Endpoints .......................................................................................................... 29 
10.2 Secondary Endpoints ...................................................................................................... 29 
11 
SPECIAL INSTRUCTIONS ................................................................................................. 29 
12 
DATA HANDLING AND RECORD KEEPING .................................................................... 29 
12.1 Source Documentation .................................................................................................. 29 
12.2 Serious Adverse Event Monitoring Form ....................................................................... 29 
12.3 Record Retention ........................................................................................................... 30 
12.4 Data Management ......................................................................................................... 30 
13 
STUDY OVERSIGHT .......................................................................................................... 30 
13.1 Data Safety Monitoring Board (DSMB) ............................................................................. 30 
13.2 Study Site Monitoring .................................................................................................... 30 
14 
STATISTICAL CONSIDERATIONS .................................................................................... 30 
14.1 Study Hypothesis ............................................................................................................ 31 
14.2 Sample Size Considerations ........................................................................................... 31 
14.3 Planned Interim Analyses ............................................................................................... 31 
14.4 Final Analysis Plan .......................................................................................................... 31 


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15 
REGISTRATION GUIDELINE ............................................................................................ 31 
16 
BIOHAZARD CONTAINMENT .......................................................................................... 31 
17 
ETHICAL AND REGULATORY CONSIDERATIONS ......................................................... 31 
17.1 Institutional Review Board ............................................................................................. 31 
17.2 Informed Consent Process ............................................................................................. 32 
17.3 Exclusion of Women, Minorities, and Children (Special Populations) ........................... 32 
17.4 Privacy and Confidentiality ............................................................................................ 32 
17.5 Future Use of Stored Specimens and Other Identifiable Data ...................................... 32 
18 
REFERENCES/ATTACHMENTS ....................................................................................... 33 
19 
APPENDICES ..................................................................................................................... 34 
Appendix I: 
Registration form ............................................................................................. 34 
Appendix II: 
Informed Consent Form .................................................................................. 34 
Appendix III: 
Data Collection Form ....................................................................................... 34 
Appendix IV: 
Serious Adverse Event Monitoring Form ........................................................ 34 
20 
SIGNATURE ................................................................................................................... ..344 
 
 
 
 
 


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DESCRIPTION OF PROTOCOL AMENDMENT 
Original Protocol Version 1.1. 20MAY2016 
Amendment Version 1.2 Dated 16JUL2017 
Amendment 1.3 Dated 28OCT2017 
Number of global amendment 
1.1 
Date of CTP revision 
20MAY2016 
Protocol Number 
FeCitrate 
Title of protocol 
Transition to Ferric Citrate among Hemodialysis and 
Peritoneal Dialysis Patients: A Phase 4 “Real World” 
Experience Study from Kaiser Permanente Southern 
California) 
To be implemented only 
after approval of the IRB  
X 
Section to be changed 
Principal Investigator 
Description of Change 
Dr. Hui Xue added 
Section to be changed 
Title Page 
Description of Change 
Amendment/Revision Section added 1.2. 
Section To be changed 
Table of Contents 
Description of change 
Table of Contents added protocol amendment 
summary to page 5 and updated table of contents 
pages 
Section to be changed 
Section 3: Study Design 
Description of change 
Added the following sentence to bullet point 3: “If 
study staff is unable to meet with patient during 
routine visit or if the patient requests more time to 
consider participation, peritoneal dialysis patients 
may be asked to return to clinic for an additional visit 
to sign the informed consent. This will only apply to 
peritoneal dialysis patients.” 
Section to be changed 
Section 9.4 Study Calendar 


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Description of change 
Footnote 4 added “If study staff is unable to meet 
with patient during routine visit or if the patient 
requests more time to consider participation, 
peritoneal dialysis patients may be asked to return to 
clinic for an additional visit to sign the informed 
consent. This will only apply to peritoneal dialysis 
patients.” 
DESCRIPTION OF PROTOCOL AMENDMENT 
Number of global amendment 
1.2 
Date of CTP revision 
16JUL2017 
Protocol Number 
FeCitrate 
Title of protocol 
Transition to Ferric Citrate among Hemodialysis and 
Peritoneal Dialysis Patients: A Phase 4 “Real 
World” Experience Study from Kaiser Permanente 
Southern California) 
Section to be changed 
Title Page 
Description of Change 
Amendment/Revision Section changed to 1.3 
Section To be changed 
Table of Contents 
Description of change 
Updated table of contents pages 
Section to be changed 
Section 4.7 Concomitant Medication/Treatments 
Description of Change 
Removed “and cinacalcet (Sensipar)”  
Section to be changed 
Section 5.1.1. removed “3 to 19 pills per day” 
Description of Change 
Revised “3 to 19 pills per day” to 3+ pills” 
Section to be changed 
Throughout the protocol 
Description of Change 
Minor grammatical, formatting, or spelling change 
were made.  
 


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DESCRIPTION OF PROTOCOL AMENDMENT 
Number of global amendment 
1.3 
Date of CTP revision 
28OCT2017 
Protocol Number 
FeCitrate 
Title of protocol 
Transition to Ferric Citrate among Hemodialysis and 
Peritoneal Dialysis Patients: A Phase 4 “Real World” 
Experience Study from Kaiser Permanente Southern 
California) 
Section to be changed 
Title Page 
Description of Change 
Amendment/Revision Section changed to 1.4 
Section To be changed 
Table of Contents 
Description of change 
Updated table of contents pages 
Section to be changed 
Description of Protocol Amendment version 1.1 
Description of Change 
Number of global amendment and date of CTP 
Version 
Section to be changed 
List of Abbreviations 
Description of Change 
Minor format change 
Section to be changed 
Section 3.0 Study Design 
Description of Change 
Added the following sentence to bullet point #3. “If 
at any time during the study, a peritoneal, dialysis 
patient changes to hemodialysis, the patient can 
continue study at the principal investigator’s 
discretion. If at any time during the study, a 
hemodialysis patient changes dialysis to peritoneal, 
the patient can continue on study at the principal 
investigator’s discretion.  In such event, patient’s 
group assignment for analysis will be determined at 
the discretion of the Principal Investigator.  Patients 
will be allowed to continue in the trial given that 
they can continue to meet all study participation 
requirements.” 
Section to be changed 
Section 7.2 Criteria for Removal from Treatment 


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Description of Change 
Added the following: “7.2.6 At the 
discretion of the principal 
investigator, a patient may be 
removed from the study if they 
initiate dialysis care at a non-
outside/Non-Kaiser Permanente 
facility.” 
Section to be changed 
Throughout the protocol 
Description of Change 
Minor grammatical, formatting, or 
spelling change were made.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
ESA 
Erythropoiesis Stimulating Agent 
CRO 
Contract Research Organization 
ESRD 
End Stage Renal Disease 
FDA 
Food and Drug Administration 
FWA 
Federalwide Assurance 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
PHI 
Protected Health Information 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 


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PROTOCOL SUMMARY 
Title 
Transition to Ferric Citrate among Hemodialysis and Peritoneal 
Dialysis Patients: A Phase 4 “Real World” Experience Study from 
Kaiser Permanente Southern California 
Short Title 
FeCitrate 
Protocol Number 
KP FeCitrate 
Study Phase 
4 
Study Site(s) 
Los Angeles Kaiser Sunset Medical Center 
Number of 
Subjects 
55  
Study Arms 
1   
Indication 
Hyperphosphatemia in end stage renal disease 
Primary Purpose 
To evaluate the efficacy of ferric citrate for control of serum 
phosphorus levels and maintenance of adequate iron stores among 
dialysis-dependent patients before and after conversion from 
traditional phosphate binders in a “real world” environment 
Overview of Study 
Design 
 prospective non-randomized cohort study of 6-9 months duration 
(active study period 6 months). 
Investigational 
Product 
Administration 
One to two tablets of Ferric Citrate phosphorus binder 
administered by mouth before every meal to prevent dietary 
phosphorus absorption. 
Eligibility Criteria 
Inclusion criteria: 
• 
On 3 + per day of calcium acetate, sevelamer, lanthanum, 
aluminum, or calcium carbonate 
• 
Mean serum phosphorus 4.0-<8.0 mg/dl for the past 6 months 
• 
No allergy to iron 
• 
Mean corrected calcium >8.0mg/dl for past 6 months 
• 
Mean PTH < 1000 pg/ml for past 6 months 


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• 
Mean ferritin < 1500 ng/ml and mean iron sat < 50% for past 6 
months 
• 
Patients with diabetes will be included 
Exclusion criteria 
• 
History of gastrointestinal bleeding within past 6 months 
• 
History of hospitalization for gastroparesis, bowel obstruction, 
or abdominal surgery within past 6 months 
• 
Active malignancy 
• 
Renal transplant 
• 
History of autoimmune disease, hemoglobinopathy, 
hemochromatosis, or sickle cell disease 
Study Endpoint 
Mean serum phosphorus levels and rate of successful phosphorus 
control (<5.5mg/dl) 6 months before and after treatment with 
ferric citrate 
Statistical 
Methods 
Not powered to detect statistical significance 


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1 INTRODUCTION 
  
1.1  
Background 
High serum phosphorus levels are associated with a greater risk of mortality among 
patients with chronic kidney disease (CKD) and non-chronic kidney disease populations(1-
5). Elevated phosphorus levels are also associated with increased cardiovascular 
complications among dialysis patients.  As renal function declines, dietary intake and 
adherence to phosphate binders becomes more and more important for phosphorus 
control and prevention of CKD-associated mineral bone disease (CKD-MB).  
 
Reduction of serum phosphorus levels by phosphate binding agents is associated with a 
lower risk of both cardiovascular and all-cause mortality in patients with end stage renal 
disease (ESRD)(6), but side effects of phosphate binders, high pill burden, and long term 
safety concerns remain an issue.  Calcium based binders are associated with vascular 
calcifications(7, 8), which led to national guidelines that limit total elemental calcium 
intake in ESRD patients.  Aluminum hydroxide and lanthanum carbonate are potential 
alternatives to calcium based binders and sevelamer carbonate/hydrochloride, but pose 
the risk for long term buildup in the body and potential untoward consequences since they 
are metals. (9, 10)  
 
While much effort is placed on dietary counseling regarding low phosphorus diets, proper 
use of phosphate binders and vitamin D analogs, a high prevalence of CKD-MB associated 
complications still exists among patients, especially dialysis dependent patients.  Valvular 
heart disease, isolated systolic hypertension, calcific uremic ateriolopathy (calciphylaxis), 
peripheral vascular disease, and hip fractures are all more common in CKD patients, 
leading to greater morbidity and mortality(11, 12).  The pathophysiology of vascular 
disease in CKD patients is complex.  It occurs as a consequence of reduced renal function, 
increases in calcium and phosphorus balance, precipitation of calcium and phosphorus and 
the uremic milieu.  Previous observations using electron beam computed tomography have 
demonstrated an association between higher calcification and cardiovascular disease.(12, 
13) 
 
Circulatory function is further compromised by declining hemoglobin levels and anemia in 
the CKD population.  The insufficient erythropoiesis that occurs as renal function declines 
likely compounds the vascular pathology that occurs in the setting of CKD-MB.  In addition, 
elevated serum phosphorus levels and associated hyperparathyroidism lead to bone 
marrow suppression, compounding the anemia. Erythropoiesis stimulating agents (ESA’s) 
are a routine part of management of patients with CKD/ESRD, but are not without adverse 
effects, including an increased risk of cardiovascular events, mortality, and malignancy.  
Current recommendations regarding use of ESA’s in ESRD patients are to use the minimum 
dose required to prevent blood transfusion.  Maintenance of adequate iron stores ensures 
adequate erythropoiesis and avoids excessive use of ESA’s. 
 


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Control of serum phosphorus levels can be a challenge for patients with ESRD and depends 
largely on patient adherence to diet and phosphate binder use.  Many patients have 
difficulty tolerating binders, possibly due to pill size and high pill burden(14, 15).  It is not 
unusual for ESRD patients to consume upwards of 10 pills per day in an effort to control 
serum phosphorus levels.  Simpler medication regimens for phosphorus control would 
likely result in improved compliance and better outcomes for patients with ESRD. 
 
1.2  
Study Medication 
 
Ferric citrate is an iron-based phosphate binder approved by the FDA for control of serum 
phosphorus levels in patients with chronic kidney disease on dialysis.  It has been shown to 
increase serum iron parameters, including ferritin, iron and TSAT. In dialysis patients treated 
with ferric citrate in a 52-week study in which IV iron could also be administered, mean (SD) 
ferritin levels rose from 593 (293) ng/mL to 895 (482) ng/mL, mean (SD) TSAT levels rose from 
31% (11) to 39% (17) and mean (SD) iron levels rose from 73 (29) mcg/dL to 88 (42) mcg/dL. 
In contrast, in patients treated with active control, these parameters remained relatively constant. 
1.3  
Preclinical Data 
Ferric citrate has already been FDA approved.  
1.4  
Clinical Data to Date 
 
Ferric citrate coordination complex (ferric citrate) is an intestinal phosphate binder that 
has been shown previously to replete iron stores, increase hemoglobin levels, and reduce 
serum phosphate levels in patients with ESRD undergoing hemodialysis. 
1.5  
Hypothesis 
We seek to determine the efficacy and potential pleotropic effects of the new FDA 
approved phosphorus binder, ferric citrate, in patients with ESRD, including both 
hemodialysis and peritoneal dialysis patients. This study is expected to expand upon 
results obtained in previous published studies, providing “real world” experience with 
ferric citrate. 
 
2 OBJECTIVES AND PURPOSE 
   
SPECIFIC AIMS 
1) To determine efficacy and tolerability of ferric citrate in dialysis-dependent patients 
treated for hyperphosphatemia 


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2) To compare dose efficacy of ferric citrate to calcium acetate and sevelamer 
carbonate for control of serum phosphorus levels 
3) To determine changes in iron saturation and ferritin after conversion to ferric 
citrate 
4) To determine iron requirements after conversion to ferric citrate 
5) To determine changes in hemoglobin after conversion to ferric citrate 
6) To determine ESA doses and requirements after conversion to ferric citrate 
  
3 STUDY DESIGN 
 Type: non-randomized, single arm, phase IV, cohort pilot study     
 Study population: end stage renal disease patients who are on chronic hemodialysis 
or peritoneal dialysis with elevated serum phosphorus.   
 55 chronic dialysis patients (28 hemodialysis and 27 peritoneal dialysis) who are 
currently using oral phosphorus binders will be enrolled.  Potential participants will 
be screened from both the chronic hemodialysis unit and the home dialysis unit at 
the LAMC site.  Potential study patients will be approached by study investigators 
during any routine visit.   If the patient consents to participation, the study 
coordinator will see patients during the same visit.  If study staff is unable to meet 
with patient during routine visit or if the patient requests more time to consider 
participation, peritoneal dialysis patients may be asked to return to clinic for an 
additional visit to sign the informed consent. This will only apply to peritoneal 
dialysis patients.  If the patient chooses not to enter the study, the reason will be 
noted by the study coordinator.  At the appropriate time in the study, the study 
coordinator will dispense the study medication, Ferric Citrate, and provide 
instructions per study protocol.  The study coordinator will meet with the 
participant every month during either a hemodialysis visit (for hemodialysis 
patients) or a monthly clinic visit (for peritoneal dialysis patients) with his/her 
provider, and laboratory values/data and study questionnaire will be updated each 
month.  If at any time during the study, a peritoneal, dialysis patient changes to 
hemodialysis, the patient can continue study at the principal investigator’s 
discretion. If at any time during the study, a hemodialysis patient changes dialysis to 
peritoneal, the patient can continue on study at the principal investigator’s 
discretion.  In such event, patient’s group assignment for analysis will be 
determined at the discretion of the Principal Investigator.  Patients will be allowed 
to continue in the trial given that they can continue to meet all study participation 
requirements. The six month period prior to enrollment will be used to evaluate the 


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participants’ baseline laboratory values and medication use, including phosphorus 
binder use.  Laboratory values and medication use will also be evaluated and 
recorded monthly during the six months of active study.  The duration of the study 
will be six months on ferric citrate. At the end of the study, the participant can be 
provided with a prescription of ferric citrate by his/her nephrologist if the 
participant wishes to continue with ferric citrate, or he/she can go back to the 
phosphorus binder used before enrolling in this study.  
3.1 
Treatment Arms 
This is a single arm study in which all participants will be changed to the study 
medication for a total of six months. 
3.2   
Study Duration 
Patients who satisfy inclusion criteria will be enrolled in the study during an initial 
period of up to 3 months.  After initial enrollment and consent, patients will 
continue for a total of 6 months on the study drug.   
4 STUDY PRODUCT INFORMATION 
4.1 
Description 
Ferric Citrate is known chemically as iron (+3), x (1, 2, 3-propanetricarboxylic acid, 2- hydroxy-
), y (H2O) x=0.70 – 0.87, y = 1.9 – 3.3. 
 
Ferric citrate’s trade name is Auryxia.  Auryxia 210 mg ferric iron tablets, equivalent to 1g 
ferric citrate, are film-coated, peach-colored, and oval-shaped tablets embossed with 
“KX52”. The inactive ingredients are pregelatinized starch and calcium stearate.  In 
addition, the film-coating contains the following inactive ingredients; hypromellose, 
titanium dioxide, triacetin, and FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake, FD&C 
Red #40/Allura Red AC Aluminum Lake, and FD&C Blue #2/Indigo Carmine Aluminum 
Lake.   
 
Mechanism of Action  
Ferric iron binds dietary phosphate in the GI tract and precipitates as ferric phosphate. Ferric 
phosphate is insoluble and is excreted out of the body in the stool. By binding phosphate in the 
GI tract and decreasing absorption, ferric citrate lowers the phosphate concentration in the 
serum.  
4.2  
Acquisition and Accountability 
Ferric Citrate will be supplied by the manufacture, Keryx Biopharmaceuticals, Inc., in 200 
tablet foil sealed bottles to the study site.  This study is to be conducted at a single site, at 
LAMC, and the medication will be stored in a secure, locked location within LAMC campus 
pharmacy that is accessible only to the study investigators and staff.  Medication will be 


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delivered every 2 months based on need.  Participants will be able to keep any unused 
investigational product already dispensed at the termination of the study.  Any medication 
that is unused or returned by participating patients will be properly disposed of with the 
aide of the study pharmacist per LAMC pharmacy’s waste medication disposal protocol.  
4.3  
Formulation, Packaging, and Labeling 
Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets 
in 400-cc high-density polyethylene bottles.    
4.4  
Storage and Stability 
Store at 20 to 25°C (68 to 77°F): excursions permitted to 15° to 30°C (59°F to 86°F)   Protect 
from moisture. 
4.5  
Dosage, Preparation and Administration 
Study medication will be dispensed in multiple of 200 tablet bottles on a monthly basis, 
based on a given participant’s phosphorus binder requirement.  Following the physician’s 
monthly dialysis rounding, patient will be seen by the study coordinator on the same day, 
and the following month’s supply of ferric citrate will be dispensed.  In center hemodialysis 
patients will be asked to bring their study drug with them to the dialysis center, where they 
will undergo a weekly pill count.  Peritoneal dialysis patients will have weekly telephone 
follow up by the study coordinator regarding medication compliance, and will have an in 
person monthly pill counting during their monthly dialysis follow up visit.  
4.6 
Toxicity and Safety Information 
 
 
Patients with iron overload syndromes (e.g., hemochromatosis) are contraindicated 
to take Ferric Citrate, as the iron absorption may lead to excessive elevation in iron stores.  
Iron levels in blood will be monitored closely on a monthly basis.  Accidental overdose of 
iron-containing products is a leading cause of fatal poisoning in children under 6 years of age, 
therefore no children are included in this study. Patients with inflammatory bowel disease or 
active, symptomatic gastrointestinal bleeding were excluded from clinical trials, therefore 
these populations are excluded from this current study.    
 
In clinical trials, adverse events reported in more than 5% of patients treated with Ferric 
Citrate, at a rate similar to the control group.  Side effects reported included diarrhea (21%), 
nausea (11%), constipation (8%), vomiting (7%), and cough (6%4) as per the package insert.     
Gastrointestinal adverse reactions were the most common reason for discontinuing Ferric 
Citrate.  The study medication is also associated with discolored feces. 
4.7 
Concomitant Medications/ Treatments 
Other non-study oral phosphorus binders are excluded from concomitant 
medications/treatments for the study due to potential impact on serum phosphorus and 
calcium levels. All other concurrent treatments are allowed. 


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5 SELECTION AND WITHDRAWAL OF PATIENTS 
5.1 Inclusion Criteria 
5.1.1 Currently using 3 + pills per day of calcium acetate, sevelamer, lanthanum, or 
calcium carbonate 
5.1.2 Mean serum phosphorus 4.0-<8.0 mg/dl for 6 months prior to enrollment 
5.1.3 No allergy to iron 
5.1.4 Mean corrected serum calcium > 8.0 mg/dl for 6 months prior to enrollment 
5.1.5 Mean PTH < 1000 pg/ml for 6 months prior to enrollment 
5.1.6 Mean ferritin < 1500 ng/ml and mean iron sat < 50% for 6 months prior to 
enrollment 
5.2 Exclusion Criteria 
 
5.2.1 
History of gastrointestinal bleeding within past 6 months 
5.2.2 
History of hospitalization for gastroparesis, bowel obstruction, or abdominal 
surgery within past 6 months 
5.2.3 
Acute kidney injury equal to or less than 3 months before the initial screening date 
5.2.4 
Active malignancy 
5.2.5 
Functioning renal transplant 
5.2.6 
Patients with iron overload syndrome (e.g., Hemochromatosis) 
5.2.7 
History autoimmune disease, hemoglobinopathy, hemochromatosis, sickle cell 
disease 
5.2.8 
Active or past history of calciphylaxis  
 
5.3 
Withdrawal Criteria 
Participants are eligible to withdraw voluntarily at any time, and will be terminated 
from the study based on any serious adverse event, loss to follow-up, kidney 
transplantation, pregnancy and/or withdrawal as determined by the study 
investigator. 
6 STRATIFICATION/ RANDOMIZATION SCHEME 
No stratification or randomization scheme is needed in this single arm study. 


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7 STUDY PRODUCT ADMINISTRATION AND TOXICITY 
MANAGEMENT PLAN 
7.1  
Administration 
 
Ferric Citrate will be administered orally with water within 30 minutes of a meal.  
Study drug dosing conversion will be based on type of phosphate binder that the 
patient is taking at the initiation of the study.  Given the binding capacity of the 
different binders (appendix table), we will make the conversion as below 
i. For calcium carbonate, calcium acetate, sevelamer carbonate 
1. 1 tablet with meals will convert to 1 tablet of ferric citrate with 
meals 
2. 2 tablets or higher will convert to 2 tablets of ferric citrate with 
meals and will be titrated up based on week 2, week 4, and 
subsequent routine monthly labs 
ii. For Lanthanum 
1. 1 or more tablets with meals will convert to 2 tablets will 
convert to 2 tablets of ferric citrate with meals and will be 
titrated up based on week 2, week 4, and subsequent routine 
monthly labs 
All subsequent phosphate binder dose adjustments will be based on decisions made by 
the nephrologists based on routine clinical laboratory results and patients subjective 
tolerability to binders.   Laboratory monitoring of baseline labs (Calcium, phosphorus, 
iron levels, ferritin, hemoglobin, hematocrit) will be every 2 weeks for the first 2 
months, and ferric citrate dose may be titrated every 2 weeks until stable phosphorus 
control is obtained.  
 
 
7.1b 
Management of IV iron during study phase  
If patient is receiving IV iron at the time active study starts (ie, start of ferric 
citrate administration), IV iron will be discontinued if the patient’s ferritin 
level is > 200 ng/ml and iron saturation is > 20%.  Otherwise IV iron may be 
continued until patient’s serum ferritin level is > 200 ng/ml and iron 


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saturation is > 20% with concomitant use of the study drug.  IV iron will not 
be used if the iron saturation is greater than 50%, even if a patient’s serum 
ferritin level falls below 200 ng/ml. 
 
If during the active study period a patient’s serum ferritin level falls below 200 
ng/ml and/or iron saturation level falls below 20%, IV iron may be restarted, at 
the discretion of the study investigator(s). 
7.2 
Criteria for Removal from Treatment 
7.2. 1 After six months of study drug use, the study drug will no longer be 
provided by Keryx free of charge.  Patients may continue with Ferric Citrate 
as their oral phosphorus binder of choice, if desired (at their own expense).  
 
7.2.2 Patients will discontinue treatment in the event of iron overload or 
any serious adverse side effect deemed attributable or possibly attributable 
to the study drug. 
 
7.2.3 Patient will be removed if he/she misses the medication continuously 
for more than 2 weeks.   
 
 
 
7.2.4 A patient will be removed from treatment if he/she receives a renal 
transplant. 
 
7.2.5 Patient will be removed from the study if consent is withdrawn or patient 
is lost to follow up. 
 
7.2.6   At the discretion of the principal investigator, a patient may 
be removed from study if they initiate dialysis care at an 
outside/Non-Kaiser Permanente facility.  
 
7.3 
Comorbidities 
 
 
Participants’ comorbid conditions will be managed by their physicians per usual protocol.  
  
8 ASSESSMENT OF EFFICACY AND SAFETY 
8.1 
Toxicity Monitoring 
Laboratory monitoring will occur on a bi-monthly basis for the first two months, 
then on a monthly basis and as needed.   Laboratories monitored will include 


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calcium, phosphorus, iron levels, ferritin, and complete blood count.  In addition, 
participants will be screened by the study coordinator either in person or via the 
phone every week to two weeks on adverse side effect monitoring.  
8.2 
Modification of Study Product Administration based on Toxicity 
Any changes in ferric citrate dosing will be at the discretion of the study 
investigators and will occur no more frequent than every 2 weeks.   If a patient’s 
absolute iron saturation level increases to greater than 50%, the study medication 
dose will be reduced by half and iron saturation and ferritin levels will be repeated 
in two weeks.  If the iron saturation level is not improved or phosphorus control is 
not achievable, then the participant will be removed from the study.  If a patient’s 
ferritin level increases to >2000 ng/ml, patient’s chart will be reviewed by two 
study investigator to assess the reason for the ferritin increase, and whether the 
participant should remain in the study.  
8.3 
Adverse Events Reporting 
 
All Adverse event reporting will follow KPSC clinical trials reporting 
guideline per KPSC CT SOP 401, Clinical Trial Regulatory Management. 
Reportable Event or Incident 
Timeframe to report to IRB 
Unanticipated death of a research subject 
that is determined by the PI to be at least 
possibly related to the study  
 
Within one business day following 
discovery and at time of continuing review  
 
Reportable Event or Incident Timeframe to 
report to IRB Internal Unanticipated 
Serious Adverse Events that meet the three 
reporting criteria  
 
Within 10 business days following 
discovery  
and at time of continuing review  
 
External Unanticipated Serious Adverse 
Events that meet the reporting criteria  
 
Within 10 business days following 
discovery  
and at time of continuing review  
 
External Unanticipated Serious Adverse 
Events that do NOT meet the reporting 
criteria (e.g., IND Safety Reports)  
 
At the time of continuing review  
 
Unanticipated Adverse Device Effect  
 
Within 10 business days following 
discovery and at time of continuing review 
 


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Breach 
Report to KPSC Privacy Officer and IRB  
immediately following discovery  
 
 Protocol Violations  
Within 10 business days following 
discovery  
and at time of continuing review  
 
Protocol Deviations 
Within 10 business days following 
discovery  
and at time of continuing review  
 
New Safety Information (e.g., updated 
investigators’ brochure containing new 
safety information of which the IRB is not 
yet aware) that meets the reporting 
criteria.  
 
Within 10 business days following 
discovery  
and at time of continuing review  
 
Emergent modifications to the IRB-
approved protocol to protect the safety, 
rights, or welfare of one or more research 
participants when there is not time to 
obtain IRB approval  
 
Within five business days of beginning  
implementation  
 
Incarceration of research a participant  
 
Within two business days following 
discovery  
 
Inspection by external regulatory agency,3 
e.g., FDA, OHRP, DOT, non-US  
 
Within two business days following 
discovery  
 
 
8.3.1 
Definitions 
 
Adverse Event (AE) is any untoward medical occurrence associated with the use 
of a drug in humans, whether or not considered drug related. 
All adverse events, including those that are reported by the patient spontaneously, 
those the study investigator observes, and those that the study investigator elicits 
in response to open-ended questions. Recorded adverse events will be assessed 
by the study investigator indicating the causal relationship of the event with the 
study drug and whether it meets the criteria for a Serious Adverse Event.  


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Some reported adverse drug reactions include diarrhea, constipation, abdominal 
discomfort, abdominal distension, duodenal ulcer, and nausea.  
Serious Adverse Event noted in prior publications included death, duodenal ulcer, 
congestive heart failure, dialysis access shunt stenosis, and infections. 
 
8.3.2 
Serious Adverse Event Reporting 
SERIOUS ADVERSE EVENT (SAE) is an adverse event or suspected adverse 
reaction if, in the view the study investigator, it meets one or more of the 
following criteria: 
• Results in death 
• Is a life-threatening adverse event (places the subject at immediate risk of 
death from the event as it occurred) 
• Results in inpatient hospitalization or prolongation of existing 
hospitalization 
• Results in a persistent or significant incapacity or substantial disruption of 
the ability to conduct normal life functions 
• An important medical event that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, 
based upon appropriate medical judgment, the event may jeopardize the 
patient and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition 
8.3.3 
Investigator Reporting: Notifying FDA 
 
Any SAE, including death from any cause, which occurs during the study and is 
deemed related or possibly related to the study drug, will be reported to the FDA 
and to Med Watch by the study investigator within 24 hours of detection of the 
SAE.  
 
Withdrawal from the trial and all therapeutic measures taken will be at the 
discretion of the Principal Investigator (PI).  All SAEs (related or of possible 
relationship to the study drug) will be followed until satisfactory resolution or 
until the PI deems the event to be chronic or the subject to be stable. 
 


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Any subject experiencing one or more SAEs will receive treatment and follow-up 
evaluations by the Investigator or will be referred to another appropriate 
physician for treatment and follow-up.  SAEs will be monitored from the time of 
consent and for up to 14 days after the subject has discontinued study drug. 
 
All adverse events, whether serious or non-serious will be followed until 
resolution (or stabilization, if applicable) or until the adverse event is 
determined by the Investigator to be no longer clinically significant.  
 
  Reporting of SAE’s to Ferric Citrate Drug Manufacturer/Supplier: 
 
Serious Adverse Events (SAE) which occur in patients receiving ferric citrate, 
from the time of randomization through and including 14 days after the last 
administration of the study drug, must be reported to Keryx Biopharmaceuticals 
within 24 hours of becoming aware of the SAE. The Investigator Sponsor will 
submit an SAE form to Keryx (available 24 hours/day, 7 days/week) to the 
following: 
 
Email:  PV_Keryx@quintiles.com   
 
Fax:     1-866-599-1342 
 
8.3.4 
Investigator Reporting: Notifying KPSC IRB 
The study investigator will also notify the KPSC Institutional Review Board (IRB) 
of any SAE within 10 business days per the KPSC IRB SOP 502, Principal 
Investigator Reportable Event and Incident Requirements. 
8.3.3 
Time Period and Frequency for Event Assessment and Follow-up 
Adverse events are collected on a weekly basis for the in center hemodialysis 
patients, and on a bi-monthly basis from the home dialysis patients, and again 
30days after the termination of the study.    
9 STUDY SCHEDULE: CLINICAL/ LABORATORY EVALUATIONS 
9.1  Study Schedule 
 9.1.1 
Screening Visit 
Screening visit will occur during the participant’s routine monthly dialysis follow 
up visit by the participant’s nephrologist.  Patients who meet the inclusion 
criteria based on chart review by the study coordinator will be approached and 


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offered to discuss the study in an opt-in fashion introduced by the patient’s 
nephrologist.   
  
 
Obtain and document consent from potential patient 
 Review medical history to determine preliminary 
eligibility based on protocol eligibility criteria 
 Obtain comprehensive medical history and limited 
physical exam from the medical history, supplemented 
by information from the patient 
 Assign participant a study ID 
 Collect blood specimens for aluminum level 
 
9.1.2 Recording of baseline data 
A baseline assessment of patient’s compliance with usual medications will be 
performed.   
The study coordinator will then review previously obtained routine monthly 
laboratory values from the dialysis unit, including complete blood count, iron 
saturation, ferritin, phosphorus, calcium, parathyroid hormone (a total of 6 
months of previous data to be reviewed).  The study coordinator will then use this 
baseline data to help determine a patient’s eligibility for participation in the active 
portion of the study, based on the criteria listed in section 5.1.  After it is 
determined that patient actually qualifies for participation in the study, the 
following will be recorded by the study coordinator: 
 
 Patient’s average weekly IV iron and erythropoiesis stimulating agent 
use (6 months of retrospective data) 
 6 months of retrospective routine laboratory data (CBC, iron 
saturation, ferritin, calcium, phosphorus, albumin, intact parathyroid 
hormone levels) will be recorded for each of the previous 6 calendar 
months 
 6 months of retrospective data regarding medication use will be 
recorded for each of the previous 6 calendar months (including 
calcitriol or other vitamin D analogs, cinacalcet, and phosphorus 
binders), including frequency and dose 
 


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After baseline data is obtained, participants will be dispensed a 1 month supply 
of the study medication, with the starting dose of 1-2 tablets per meal, three 
times a day.  This will mark the start of the active study drug phase.  
9.1.3  Study phase monthly visit 1-5 (V1, V2, V3, V4, V5) ± 14 days 
 
Participants will be evaluated in person by the study coordinator on a 
monthly visit, during the same visit when the subject is seen by his/her 
dialysis provider.  Study records will be updated with the following: 
 Limited physical exam from the dialysis provider’s notes 
 Updates in medical history 
 Monthly routine dialysis laboratory values from the dialysis 
unit, including complete blood count, iron saturation, 
ferritin, phosphorus, calcium, parathyroid hormone 
 Provide blood test tube to draw monthly aluminum level 
 Update patient’s IV iron and erythropoiesis stimulating agent use.  
 Assess for study medication compliance via pill counting 
 Dispense study medication supply for the following month 
 Assess for adverse events 
 
 
9.1.4  Lab draw 2 weeks and 6 weeks into the study (L0.5, L1.5) with 
optional visit ± 7 days 
 
Participant will have lab draw 2 weeks into the study, and possibly 
again 6 weeks into the study (if deemed necessary by the study 
investigator), in between their routine monthly labs, to help adjust 
the study drug dose to control the serum phosphorus level. 
 Collect blood specimens at dialysis unit for complete blood 
count, iron saturation, ferritin, phosphorus, calcium 
 Study coordinator will review laboratory tests with study 
investigator to assess if study drug dose adjustment is 
needed. 
 Optional visit by study coordinator with the patient to 
review study medication dosage change 
9.1.5   Weekly in-center & bi-monthly home dialysis follow up ± 7 days 
 


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Participants who are in center dialysis patients will be visited by 
the study coordinator once a week for pill count and adverse side 
effect evaluation.  Participants who are home dialysis patients will 
have bi-monthly telephone follow up by the study coordinator to 
assess medication compliance and adverse side effect evaluation.  
9.1.4 Withdrawal/ Final Visit (V6) ± 14 days 
 
At end of 6 months of study drug use, or patient’s withdrawal from 
the study, study coordinator will perform the following: 
 Update comprehensive medical history 
 Update limited physical exam from dialysis provider’s note 
 Update medical history from health records 
 Collect blood specimens for aluminum level test 
 Adverse event assessment 
 
 Update laboratory values from the dialysis unit, including complete 
blood count, iron saturation, ferritin, phosphorus, calcium, 
parathyroid hormone 
 Update patient’s average weekly IV iron and erythropoiesis 
stimulating agent use.  
 Perform final pill count to assess medication compliance 
 Collect unused investigational product from patient who withdrew 
from the study 
 Record patient preference for oral phosphorus binder at the end of 
study. 
Any participant who wishes to continue with the study drug as their oral 
phosphorus binder of choice will be provided a prescription for Ferric Citrate.  
Participants who wish to return to their previous phosphorus binder will be 
returned to their original binder.  
9.1.5 30 day post study termination follow-up ± 14 days 
Study coordinator will follow up with each participant 30 days after termination 
or study by patient withdrawal or study completion.  Following assessment will 
be completed: 


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 Adverse event assessment 
 Laboratory values from patient’s dialysis unit on complete 
blood count, iron saturation, ferritin, phosphorus, calcium 
 
9.2 
Clinical Evaluations 
Laboratory testing will include: complete blood count, iron saturation, ferritin, 
phosphorus, calcium, parathyroid hormone, and aluminum level 
 
Symptoms evaluation will include: any hospitalizations, infections, GI bleed, 
dialysis access complications, diarrhea, constipation, abdominal discomfort, 
abdominal distension, duodenal ulcer, nausea, and stool color changes.   
9.3 
Laboratory Evaluations 
 
Routine dialysis laboratory values will be collected from the patient’s dialysis unit on a 
monthly basis per current standard of care.  At week 2 and week 6, additional complete 
blood count, iron saturation, and ferritin levels will be collected at the patient’s dialysis 
unit.  Six aluminum levels will be drawn for each participant over the course of the study.  
Aluminum level tests will be collected in a single vial (royal blue top tube, approximately 
4 ml of blood) by the study coordinator and transported on ice to the LAMC laboratory.  
 
 


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9.4 
Study Calendar 
 
Study Procedures 
Screening 
Baseline  
Data to 
be 
collected 
 
Study phase 
monthly Visit # 
1-5, V1-V5  1 
 
Laboratory  
on week 2 and  
week 6 2 
weekly in-center 
& bi-monthly 
home dialysis  
follow up 
End of  
Treatment 
30 post  
follow up  
Signed Consent Form 
X 4 
 
 
 
 
 
 
Assessment of 
Eligibility 
X 
X 
 
 
 
 
 
Comprehensive 
History 
X 
 
 
 
 
X 
 
Limited Physical Exam 
X 
 
X 
 
 
X 
 
Update Medical 
History 
 
X 
X 
 
 
X 
 
Complete Blood Count 
X 
X 
X 
X 
 
X 
 
Iron saturation   
X 
X 
X 
X 
 
X 
 
Ferritin 
X 
X 
X 
X 
 
X 
 
Phosphorus 
X 
X 
X 
X 
 
X 
 
Calcium  
X 
X 
X 
X 
 
X 
 
IV iron use 
X 
X 
X 
 
 
X 
 
Parathyroid Hormone 
 (iPTH) 
X 
X 
X 
 
 
X 
 
Aluminum level3 
 
 
X 
 
 
 
 
 Mean weekly  
ESA agent dose 
X 
X 
X 
 
 
X 
 
Medication dispensed   
 
 
X 
 
 
 
 
Medication compliance 
 update 
 
 
X 
 
X 
X 
 
Adverse Event 
Assessment 
 
X 
X 
 
X 
X 
X 
  
1        Each visit will correspond with monthly hemodialysis or peritoneal dialysis 
monthly laboratory result round 
2        Blood test will be drawn during routine hemodialysis.  Home dialysis patients 
will be asked to go to any KPSC laboratory (normal routine for these patients).  
3 
Aluminum level blood tube will be brought by study coordinator to be drawn at 
hemodialysis with the patient’s regular monthly labs.  Aluminum test tube will 
be transported on ice to the LAMC laboratory.  Home dialysis patients will be 
referred to any KPSC laboratory for aluminum testing, when needed.  
4 
Screening visit: If study staff is unable to meet with patient during routine visit 
or if the patient requests more time to consider participation, peritoneal dialysis 
patients may be asked to return to clinic for an additional visit to sign the 
informed consent. This will only apply to peritoneal dialysis patients. 


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10 CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS 
10.1 
Primary Endpoints 
 
Mean serum phosphorus levels and rate of control (<5.5mg/dl) 6 months before and after 
treatment with ferric citrate, including PTH, calcium, iron saturation, ferritin, hemoglobin and 
aluminum levels 
 
10.2 
Secondary Endpoints 
i. 
Total cumulative and average weekly dose, number of doses of iv iron 
administered before and after treatment with ferric citrate 
ii. 
Total ESA dose and mean weekly dose administered 6 months before and 
after ferric citrate treatment 
iii. 
Total dose of ferric citrate and average number of pills/day required to 
maintain phosphorus control compared to previous dose and pill burden 
with binder 
iv. 
Compare serious adverse events including tolerability of ferric citrate 
compared to previous binder 
 
11 SPECIAL INSTRUCTIONS 
N/A 
12 DATA HANDLING AND RECORD KEEPING 
12.1 
Source Documentation 
Electronic medical records, worksheets, study questionnaires will be used, and all 
paper material will be kept in a locked, secure office on LAMC campus.  All electronic 
records will be kept only on KPSC approved electronic device with encryption and 
password protection, stored in secure KPSC buildings.   
12.2 
Serious Adverse Event Monitoring Form 
Serious adverse event monitoring form will be de-identified, scanned electronically, 
and shared with the study sponsor.  Original forms will be kept at LAMC with all 
other sources documents.    


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12.3 
Record Retention 
 
All paper records will be scanned into electronic files, and paper records will be 
destroyed after 2 years via KPSC’s secure recycling (bins are kept locked and papers 
shredded).  All electronic data containing any personal identifying information such as 
name, contact telephone number, will be permanently deleted after 24 months.  All de-
identified study data will be maintained for future research.  Data containing personal 
identifiers will be housed in a separate (also password protected) database from those 
with study/clinical information to maximize participant anonymity.  
12.4 
Data Management 
Study data will only be accessible to IRB approved personnel.  All data will be stored 
on KPSC issued computers and KPSC computer server with encryption and 
password protection.   
13 STUDY OVERSIGHT 
13.1 Data Safety Review Panel 
In this pilot study with an FDA approved medication, a modified Data Safety Review 
Panel will be established with 2 study investigators and one non-study nephrologist.  
The Data Safety Review Panel will meet on a quarterly basis to evaluate any adverse 
events, including patients whose serum ferritin increased to >1500.   If Data Safety 
Review Panel identifies new drug related adverse event, reporting will follow per 
previously outlined protocol.   Study coordinator will help to keep records of the 
Data Safety Review Panel meetings.  
13.2 
Study Site Monitoring 
Study investigators are responsible for study site monitoring and supervision of the 
study coordinator.  Participant records will be reviewed on an intermittent basis to 
ensure proper and clear record keeping by the study coordinator.  Study 
investigator will also be responsible for resolving any identified issues. 
14 STATISTICAL CONSIDERATIONS 
In this pilot study, the goal is to assess the feasibility of transitioning from current oral 
phosphorus binders to the newly FDA approved iron based oral phosphorus binder, 
and identify challenges encountered in the real world, not previously seen in stringent 
clinical trial settings.    


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14.1 
Study Hypothesis 
We hypothesize that the majority of patients on chronic dialysis, who do not have a 
contraindication to oral iron supplements, can be successfully transitioned to the new 
iron based oral phosphorus binder, Ferric Citrate. 
14.2 
Sample Size Considerations 
 
 
 N/A 
14.3 
Planned Interim Analyses 
N/A 
14.4 
Final Analysis Plan 
N/A 
15 REGISTRATION GUIDELINE 
Forms and records needed for registration:  Informed Consent, Registration/Eligibility 
Worksheet, baseline data collection sheet.  All participants will be given a Bill of Rights 
along with one copy of the Informed Consent to take home, as well as leaving a signed 
copy of the informed consent for study files and patient’s medical chart.   
16 BIOHAZARD CONTAINMENT 
Participants are able to keep any used study medication at the end of the study, and to 
use the medication with his/her nephrologist’s supervision.  Any returned medication 
and left over study medication will be disposed of per LAMC pharmacy waste 
medication disposal protocol in an environmentally safe and responsible fashion. 
17 ETHICAL AND REGULATORY CONSIDERATIONS 
17.1 
Institutional Review Board 
This study will fall under the jurisdiction of the KPSC Institutional Review Board 
(IRB).  Any changes or updates to study protocol will be formally submitted to the 
IRB, and only IRB approved personnel will have access to study data.  Adverse 
report will follow IRB guidelines as previously outlined under the section of Adverse 
Reporting.   


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17.2 
Informed Consent Process 
All institutional and Federal regulations concerning the Informed Consent form will 
be fulfilled.  The study will be conducted in adherence to ICH Good Clinical Practice. 
Written informed consent, in compliance with 21 CFR 50 will be obtained before 
any study-related procedures are initiated. Informed consent will be obtained from 
each patient or patient’s legally authorized representative. Informed consent 
includes the principle that it is critical that the individual be informed about the 
potential risks and benefits of participating in this study. This information will allow 
individuals to make a personal risk-versus-benefit decision and understand the 
following general principles: 
1. Participation in this program is entirely voluntary. 
2. Patients may withdraw from participation in this program at any time 
without penalty or loss of benefits to which they are otherwise entitled. 
3. Refusal to participate in this study involves no penalty. 
4. The individual is free to ask any questions that will allow him/her to 
understand the nature of this study. 
17.3 
Exclusion of Women, Minorities, and Children (Special Populations) 
In this small pilot study, pregnant women are excluded, as end stage renal failure 
and uremia is usually not compatible with pregnancy, and very few women become 
pregnant on dialysis.  Racial and ethnic minorities are included.  Children are 
excluded as the dialysis units are adult dialysis units without pediatric patients.   
  
17.4 
Privacy and Confidentiality 
Participant privacy will be protected with the highest regards.  All paper containing 
personal identifying information will be disposed in KPSC secure paper shred boxes, 
after they are scanned into the computer.   A separate file containing the matching 
personal identifying information and the assigned study ID will be kept on a password 
protected secure KPSC server, and accessed only on KPSC LAMC campus through 
secure desktop computers.  
17.5 
Future Use of Stored Specimens and Other Identifiable Data 
No biology specimens will be stored.  All identifiable Data will be destroyed within 
12 months after the completion of the study.   


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18 REFERENCES/ATTACHMENTS 
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Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus 
and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a 
national study. Am J Kidney Dis. 1998;31(4):607-17. 
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Chang AR, Lazo M, Appel LJ, Gutierrez OM, Grams ME. High dietary phosphorus 
intake is associated with all-cause mortality: results from NHANES III. Am J Clin Nutr. 
2014;99(2):320-7. 
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Naves-Diaz M, Passlick-Deetjen J, Guinsburg A, Marelli C, Fernandez-Martin JL, 
Rodriguez-Puyol D, et al. Calcium, phosphorus, PTH and death rates in a large sample of 
dialysis patients from Latin America. The CORES Study. Nephrol Dial Transplant. 
2011;26(6):1938-47. 
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Sim JJ, Bhandari SK, Smith N, Chung J, Liu IL, Jacobsen SJ, et al. Phosphorus and risk 
of renal failure in subjects with normal renal function. Am J Med. 2013;126(4):311-8. 
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Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, et al. Mortality 
risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: 
the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 
2008;52(3):519-30. 
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Cannata-Andia JB, Fernandez-Martin JL, Locatelli F, London G, Gorriz JL, Floege J, et 
al. Use of phosphate-binding agents is associated with a lower risk of mortality. Kidney 
Int. 2013;84(5):998-1008. 
7. 
Chertow GM, Raggi P, Chasan-Taber S, Bommer J, Holzer H, Burke SK. Determinants 
of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 
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8. 
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery 
calcification in young adults with end-stage renal disease who are undergoing dialysis. N 
Engl J Med. 2000;342(20):1478-83. 
9. 
Smith AJ, Faugere MC, Abreo K, Fanti P, Julian B, Malluche HH. Aluminum-related 
bone disease in mild and advanced renal failure: evidence for high prevalence and 
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cardiovascular system. Circulation. 2007;116(1):85-97. 
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Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. Mortality effect of coronary 
calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int. 
2007;71(5):438-41. 
13. 
Haydar AA, Hujairi NM, Covic AA, Pereira D, Rubens M, Goldsmith DJ. Coronary 
artery calcification is related to coronary atherosclerosis in chronic renal disease patients: 
a study comparing EBCT-generated coronary artery calcium scores and coronary 
angiography. Nephrol Dial Transplant. 2004;19(9):2307-12. 
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Arenas MD, Malek T, Gil MT, Moledous A, Alvarez-Ude F, Reig-Ferrer A. Challenge of 
phosphorus control in hemodialysis patients: a problem of adherence? J Nephrol. 
2010;23(5):525-34. 


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15. 
Chiu YW, Teitelbaum I, Misra M, de Leon EM, Adzize T, Mehrotra R. Pill burden, 
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Dwyer JP, Sika M, Schulman G, Chang IJ, Anger M, Smith M, et al. Dose-response and 
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Yokoyama K, Hirakata H, Akiba T, Fukagawa M, Nakayama M, Sawada K, et al. Ferric 
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Umanath K, Jalal DI, Greco BA, Umeukeje EM, Reisin E, Manley J, et al. Ferric Citrate 
Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD. J Am Soc 
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Rodby R, Umanath K, Niecestro R, Jackson JH, Sika M, Lewis JB, et al. Phosphorus 
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19 APPENDICES 
Appendix I: 
Registration form 
Appendix II: 
Informed Consent Form 
Appendix III: 
Data Collection Form 
Appendix IV: 
Serious Adverse Event Monitoring Form 
 
20 SIGNATURE 
 This study will be performed in compliance with Good Clinical Practices, including the 
archiving of essential documents.  
 
Name of Principal 
Investigator: 
 
Department/Specialty: 
 
Study Site/ Location Name: 
 
Site Address: 
 


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City, State and Zip code: 
 
Phone 
Number: 
 
 
 
Signature & Date: