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A 58-Week Safety and Efficacy Trial of Ferric Citrate in Patients With ESRD on Dialysis

Sponsor
Keryx Biopharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01191255
Collaborator
(none)
441
Enrollment
56
Locations
3
Arms
28.1
Duration (Months)
7.9
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is up to a 58 week study comparing ferric citrate to active control for 52 weeks in ESRD dialysis patients, and subsequently comparing ferric citrate to placebo for 4 weeks.

Condition or Disease Intervention/Treatment Phase
  • Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo
 Phase 3

Detailed Description

This trial is a three-period, multicenter, safety and efficacy clinical trial. The first period is a two-week Washout Period, the second period is a 52-week randomized, open-label, active control Safety Assessment Period, and the third period is a four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period in only the patients who were randomized to treatment with ferric citrate during the Safety Assessment Period. The primary objectives of this trial are to determine the long-term safety over 52 weeks of up to twelve (12) caplets/day of KRX-0502 (ferric citrate) in patients with ESRD undergoing either hemodialysis or peritoneal dialysis and to determine the efficacy of KRX-0502 (ferric citrate) in the four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period.

Study Design

Study Type:
Interventional
Actual Enrollment :
441 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
A Three-Period, 58-Week Safety and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD) on Dialysis
Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Jan 1, 2013
Actual Study Completion Date :
Feb 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Active Control

PhosLo (calcium acetate) Renvela (sevelamer carbonate)

Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo
All intervention doses will be based on serum phosphorus levels and/or drug label requirements
Other Names:
  • PhosLo
  • Renvela
  • KRX-0502
  • Zerenex

    		•
    Placebo Comparator: Placebo

    Placebo

    Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo
    All intervention doses will be based on serum phosphorus levels and/or drug label requirements
    Other Names:
  • PhosLo
  • Renvela
  • KRX-0502
  • Zerenex

    		•
    Experimental: KRX-0502 (Ferric Citrate)

    ferric citrate

    Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo
    All intervention doses will be based on serum phosphorus levels and/or drug label requirements
    Other Names:
  • PhosLo
  • Renvela
  • KRX-0502
  • Zerenex

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Mean Serum Phosphorus From Baseline (Week 52) to the End of the Efficacy Assessment Period (EAP; Week 56) [4 weeks]

      Patients who completed the 52-week Safety Assessment Period (SAP) on KRX-0502 (ferric citrate) were randomized in a 1:1 ratio to receive either KRX-0502 (ferric citrate) or Placebo for 4 weeks.

    Secondary Outcome Measures

    1. Change in Mean Serum Ferritin From Baseline to Week 52 [52 weeks]

    2. Change in Mean Serum Transferrin Saturation (TSAT) From Baseline to the End of the Safety Assessment Period (Week 52) [52 weeks]

    3. IV Iron Analysis [52 weeks]

      Full Analysis Population, cumulative IV Iron administration from Baseline to the end of the Safety Assessment Period (Week 52)

    4. ESA Analysis [52 weeks]

      Full analysis population, cumulative Erythropoiesis-stimulating agent (ESA) administration from baseline to the end of the Safety Assessment Period (Week 52)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Males or non-pregnant, non-breast-feeding females

    2. Age ≥18 years

    3. On thrice-weekly hemodialysis or on peritoneal dialysis for at least the previous three months prior to Screening

    4. Serum phosphorus ≥6.0 mg/dL for study entry

    5. Taking less than 3-18 pills/day of current phosphate binder

    6. Willing to be discontinued from current phosphate binder(s) and initiated on ferric citrate

    7. Willing and able to give informed consent

    8. Life expectancy >1 year

    Exclusion Criteria:

    1. Parathyroidectomy within six months prior to Screening

    2. Actively symptomatic gastrointestinal bleeding or inflammatory bowel disease

    3. History of multiple drug allergies or intolerances

    4. History of malignancy in the last five years (treated cervical or non-melanomatous skin cancer may be permitted if approved by CCC)

    5. Previous intolerance to oral ferric citrate

    6. Intolerance to oral iron-containing products

    7. Psychiatric disorder that interferes with the patient's ability to comply with the study protocol

    8. Inability to tolerate oral drug intake

    9. Intolerance to calcium acetate and sevelamer carbonate

    10. Any other medical condition that renders the patient unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the patient

    11. Receipt of any investigational drug within 30 days of Screening Visit (Visit 0)

    12. Inability to cooperate with study personnel or history of noncompliance

    13. Unsuitable for this trial per Investigator's clinical judgment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Southwest Clinical Research Institute, LLC Tempe Arizona United States 85284
    2 Tower Nephrology Medical Group Los Angeles California United States 90048
    3 Veterans Administration Greater Los Angeles Healthcare System, West Los Angeles Los Angeles California United States 90073
    4 Apex Research of Riverside Riverside California United States 92505
    5 American Institute of Research Whittier California United States 90603
    6 University of Colorado Denver Aurora Colorado United States 80045
    7 Western Nephrology Westminster Colorado United States 80031
    8 PAB Clinical Research Brandon Florida United States 33511
    9 Mayo Clinic Jacksonville Florida United States 32216
    10 ASA Clinical Research, LLC Jupiter Florida United States 33458
    11 Ocala Kidney Group Ocala Florida United States 34471
    12 Pines Clinical Research, Inc. Pembroke Pines Florida United States 33028
    13 Kidney Care Associates, LLC Augusta Georgia United States 30901
    14 Atlanta Nephrology Referral Center Decatur Georgia United States 30030
    15 Circle Medical Management Chicago Illinois United States 60607
    16 Nephrology Specialists, PC Michigan City Indiana United States 46360
    17 LSU Health Sciences Center Section of Nephrology and Hypertension Department of Internal Medicine New Orleans Louisiana United States 70112
    18 Rockville Dialysis Center Rockville Maryland United States 20850
    19 Tufts Medical Center Boston Massachusetts United States 02111
    20 Pioneer Valley Nephrology Holyoke Massachusetts United States 01040
    21 Western New England Renal & Transplant Associates Springfield Massachusetts United States 01107
    22 Henry Ford Hospital Detroit Michigan United States 48202
    23 Michigan Kidney Consultants, PC Pontiac Michigan United States 48341
    24 Nephrology Hypertension Clinic Southgate Michigan United States 48195
    25 Kansas City VA Medical Center Kansas City Missouri United States 64128
    26 Brookdale Physician's Dialysis Associates Brooklyn New York United States 11212
    27 Mountain Kidney and Hypertension Associates, PA Asheville North Carolina United States 28801
    28 Metrolina Nephrology Associates, PA Charlotte North Carolina United States 28207
    29 Duke University Medical Center Division of Nephrology Durham North Carolina United States 27705
    30 Trial Management Associates Wilmington North Carolina United States 28401
    31 Wake Forest University School of Medicine Winston Salem North Carolina United States 27157
    32 Clinical Research Limited Canton Ohio United States 44718
    33 Division of Nephrology and Hypertension Department of Internal Medicine University of Cincinnati College of Medicine Cincinnati Ohio United States 45267
    34 Cleveland Clinic Foundation Q7-150 Nephrology Cleveland Ohio United States 44195
    35 The Ohio State University Division of Nephrology Columbus Ohio United States 43210
    36 DaVita Oklahoma City Oklahoma United States 73116
    37 University of Pennsylvania Health System Philadelphia Pennsylvania United States 19104
    38 Southeast Renal Research Institute Nephrology Associates Chattanooga Tennessee United States 37404
    39 Nephrology Associates, PC Nashville Tennessee United States 37205
    40 Vanderbilt University Medical Center Clinical Trials Center Nashville Tennessee United States 37232-1371
    41 UT Southwestern Medical Center at Dallas Dallas Texas United States 75390
    42 Kidney Associates Houston Texas United States 77030
    43 Nephrology, PA Houston Texas United States 77030
    44 Kidney Specialists of North Houston, PLLC The Woodlands Texas United States 77384
    45 University of Utah Health Sciences Center Salt Lake City Utah United States 84132
    46 University of Vermont/ Fletcher Allen Health Care; Renal Services Burlington Vermont United States 05401
    47 Nephrology Clinical Research Center Charlottesville Virginia United States 22908
    48 Clinical Research & Consulting Center, LLC Fairfax Virginia United States 22030
    49 Nephrology Associates of Northern Virginia, Inc. Fairfax Virginia United States 22033
    50 Peninsula Kidney Associates Hampton Virginia United States 23666
    51 McGuire VA Medical Center Richmond Virginia United States 23249
    52 Medical College of Wisconsin Froedert Memorial Lutheran Hospital Division of Nephrology Milwaukee Wisconsin United States 53226
    53 Department of Nephrology and Hypertension Brazilai Medical Center Ashkelon Israel
    54 Tel Aviv Sourasky Medical Center Nephrology Department Tel Aviv Israel
    55 RCMI-Clinical Research Center Medical Sciences Campus University of Puerto Rico Rio Piedras Puerto Rico 00936-5067
    56 Puerto Rico Renal Health & Research Center, Inc/ Atlantic Healthcare Group, Inc Trujillo Alto Puerto Rico 00976

    Sponsors and Collaborators

    • Keryx Biopharmaceuticals

    Investigators

    • Study Chair: Julia B Lewis, MD, Collaborative Study Group
    • Study Chair: Samuel Blumenthal, MD, Collaborative Study Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Keryx Biopharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01191255
    Other Study ID Numbers:
    • KRX-0502-304
    • NCT01510106
    First Posted:
    Aug 30, 2010
    Last Update Posted:
    Dec 10, 2014
    Last Verified:
    Dec 1, 2014
    Keywords provided by Keryx Biopharmaceuticals
    ESRD
    end-stage renal disease
    dialysis
    hemodialysis
    peritoneal dialysis
    hemodialysis (HD)
    peritoneal dialysis (PD)
    chronic renal insufficiency
    phosphate binder
    kidney failure
    renal failure
    Additional relevant MeSH terms:
    Renal Insufficiency
    Hyperphosphatemia
    Sevelamer

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Only subjects that completed the SAP on KRX-0502 were eligible to be included in the EAP in the EAP, subjects received only Placebo or KRX-0502-EAP 3 Subjects switched from 'Active Control' to KRX-0502 during the SAP and were randomized into the EAP In the 'Active Control' group, a combination of phosphate binders was allowed
    Arm/Group Title Active Control-SAP KRX-0502 (Ferric Citrate)-SAP Placebo-EAP KRX-0502 (Ferric Citrate)-EAP
    Arm/Group Description Patients received either PhosLo (calcium acetate), Renvela (sevelamer carbonate), or a combination of these treatments during a 52-week Safety Assessment Period. Patients received KRX-0502 (ferric citrate) during a 52-week Safety Assessment Period. Patients that completed the 52-week Safety Assessment Period were randomized to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period.
    Period Title: Safety Assessment Period
    STARTED 149 292 0 0
    Safety Population 149 289 0 0
    COMPLETED 111 193 0 0
    NOT COMPLETED 38 99 0 0
    Period Title: Safety Assessment Period
    STARTED 0 0 96 96
    COMPLETED 0 0 70 90
    NOT COMPLETED 0 0 26 6

    Baseline Characteristics

    Arm/Group Title Active Control-SAP KRX-0502 (Ferric Citrate)-SAP Placebo-EAP KRX-0502 (Ferric Citrate)-EAP Total
    Arm/Group Description Patients received either PhosLo (calcium acetate), Renvela (sevelamer carbonate), or a combination of these treatments during a 52-week Safety Assessment Period. Patients received KRX-0502 (ferric citrate) during a 52-week Safety Assessment Period. Patients that completed the 52-week Safety Assessment Period were randomized to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Total of all reporting groups
    Overall Participants 146 281 91 91 609
    Age, Customized (participants) [Number]
    Age <65 years (SAP)
    118
    80.8%
    223
    79.4%
    0
    0%
    0
    0%
    341
    56%
    Age >= 65 years (SAP)
    28
    19.2%
    58
    20.6%
    0
    0%
    0
    0%
    86
    14.1%
    Age <65 years (EAP)
    0
    0%
    0
    0%
    77
    84.6%
    73
    80.2%
    150
    24.6%
    Age >= 65 years (EAP)
    0
    0%
    0
    0%
    14
    15.4%
    18
    19.8%
    32
    5.3%
    Sex/Gender, Customized (participants) [Number]
    Female (SAP)
    62
    42.5%
    106
    37.7%
    0
    0%
    0
    0%
    168
    27.6%
    Male (SAP)
    84
    57.5%
    175
    62.3%
    0
    0%
    0
    0%
    259
    42.5%
    Female (EAP)
    0
    0%
    0
    0%
    77
    84.6%
    73
    80.2%
    150
    24.6%
    Male (EAP)
    0
    0%
    0
    0%
    14
    15.4%
    18
    19.8%
    32
    5.3%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino (SAP)
    23
    15.8%
    41
    14.6%
    0
    0%
    0
    0%
    64
    10.5%
    Not Hispanic or Latino (SAP)
    123
    84.2%
    239
    85.1%
    0
    0%
    0
    0%
    362
    59.4%
    Unknown or not reported (SAP)
    0
    0%
    1
    0.4%
    0
    0%
    0
    0%
    1
    0.2%
    Hispanic or Latino (EAP)
    0
    0%
    0
    0%
    14
    15.4%
    9
    9.9%
    23
    3.8%
    Not Hispanic or Latino (EAP)
    0
    0%
    0
    0%
    77
    84.6%
    82
    90.1%
    159
    26.1%
    Unknown or not reported (EAP)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    American Indian or Alaska Native (SAP)
    1
    0.7%
    2
    0.7%
    0
    0%
    0
    0%
    3
    0.5%
    Asian (SAP)
    1
    0.7%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    Native Hawaiian or Other Pacific Islander (SAP)
    2
    1.4%
    0
    0%
    0
    0%
    0
    0%
    2
    0.3%
    Black or African American (SAP)
    77
    52.7%
    153
    54.4%
    0
    0%
    0
    0%
    230
    37.8%
    White (SAP)
    61
    41.8%
    114
    40.6%
    0
    0%
    0
    0%
    175
    28.7%
    More Than One Race (SAP)
    0
    0%
    1
    0.4%
    0
    0%
    0
    0%
    1
    0.2%
    Unknown or Not Reported (SAP)
    4
    2.7%
    11
    3.9%
    0
    0%
    0
    0%
    15
    2.5%
    American Indian or Alaska Native (EAP)
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    1
    0.2%
    Asian (EAP)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander (EAP)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American (EAP)
    0
    0%
    0
    0%
    48
    52.7%
    59
    64.8%
    107
    17.6%
    White (EAP)
    0
    0%
    0
    0%
    39
    42.9%
    28
    30.8%
    67
    11%
    More Than One Race (EAP)
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    1
    0.2%
    Unknown or Not Reported (EAP)
    0
    0%
    0
    0%
    2
    2.2%
    4
    4.4%
    6
    1%

    Outcome Measures

    1. Primary Outcome
    Title Change in Mean Serum Phosphorus From Baseline (Week 52) to the End of the Efficacy Assessment Period (EAP; Week 56)
    Description Patients who completed the 52-week Safety Assessment Period (SAP) on KRX-0502 (ferric citrate) were randomized in a 1:1 ratio to receive either KRX-0502 (ferric citrate) or Placebo for 4 weeks.
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population (LOCF)
    Arm/Group Title Active Control-SAP KRX-0502 (Ferric Citrate)-SAP Placebo-EAP KRX-0502 (Ferric Citrate)-EAP
    Arm/Group Description Patients received either PhosLo (calcium acetate), Renvela (sevelamer carbonate), or a combination of these treatments during a 52-week Safety Assessment Period. Patients received KRX-0502 (ferric citrate) during a 52-week Safety Assessment Period. Patients that completed the 52-week Safety Assessment Period were randomized to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period.
    Measure Participants 0 0 91 91
    Baseline (Week 52)
    5.44
    (1.459)
    5.12
    (1.189)
    End of EAP (Week 56)
    7.23
    (1.784)
    4.89
    (1.291)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-EAP, KRX-0502 (Ferric Citrate)-EAP
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The P-value for the change in mean serum phosphorus was calculated via an ANCOVA model with treatment as the fixed effect and Week-52-baseline as the co-variate.
    Method ANCOVA
    Comments
    2. Secondary Outcome
    Title Change in Mean Serum Ferritin From Baseline to Week 52
    Description
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population (LOCF)
    Arm/Group Title Active Control-SAP KRX-0502 (Ferric Citrate)-SAP Placebo-EAP KRX-0502 (Ferric Citrate)-EAP
    Arm/Group Description Patients received either PhosLo (calcium acetate), Renvela (sevelamer carbonate), or a combination of these treatments during a 52-week Safety Assessment Period. Patients received KRX-0502 (ferric citrate) during a 52-week Safety Assessment Period. Patients that completed the 52-week Safety Assessment Period were randomized to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period.
    Measure Participants 137 253 0 0
    Baseline
    609.50
    (307.689)
    592.80
    (292.863)
    End of SAP (Week 52)
    631.87
    (368.919)
    894.88
    (481.788)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Active Control-SAP, KRX-0502 (Ferric Citrate)-SAP
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The P-value for the change in mean serum Ferritin were created via an ANCOVA model with treatment as the fixed effect and Study-baseline as the co-variate.
    Method ANCOVA
    Comments
    3. Secondary Outcome
    Title Change in Mean Serum Transferrin Saturation (TSAT) From Baseline to the End of the Safety Assessment Period (Week 52)
    Description
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population (LOCF)
    Arm/Group Title Active Control-SAP KRX-0502 (Ferric Citrate)-SAP Placebo-EAP KRX-0502 (Ferric Citrate)-EAP
    Arm/Group Description Patients received either PhosLo (calcium acetate), Renvela (sevelamer carbonate), or a combination of these treatments during a 52-week Safety Assessment Period. Patients received KRX-0502 (ferric citrate) during a 52-week Safety Assessment Period. Patients that completed the 52-week Safety Assessment Period were randomized to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period.
    Measure Participants 137 252 0 0
    Baseline
    30.8
    (11.57)
    31.3
    (11.21)
    End of SAP (Week 52)
    29.7
    (11.43)
    39.2
    (16.78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Active Control-SAP, KRX-0502 (Ferric Citrate)-SAP
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    4. Secondary Outcome
    Title IV Iron Analysis
    Description Full Analysis Population, cumulative IV Iron administration from Baseline to the end of the Safety Assessment Period (Week 52)
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Active Control-SAP KRX-0502 (Ferric Citrate)-SAP Placebo-EAP KRX-0502 (Ferric Citrate)-EAP
    Arm/Group Description Patients received either PhosLo (calcium acetate), Renvela (sevelamer carbonate), or a combination of these treatments during a 52-week Safety Assessment Period. Patients received KRX-0502 (ferric citrate) during a 52-week Safety Assessment Period. Patients that completed the 52-week Safety Assessment Period were randomized to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period.
    Measure Participants 138 271 0 0
    Median (Full Range) [mg/day]
    3.83
    1.87
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Active Control-SAP, KRX-0502 (Ferric Citrate)-SAP
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    5. Secondary Outcome
    Title ESA Analysis
    Description Full analysis population, cumulative Erythropoiesis-stimulating agent (ESA) administration from baseline to the end of the Safety Assessment Period (Week 52)
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Active Control-SAP KRX-0502 (Ferric Citrate)-SAP Placebo-EAP KRX-0502 (Ferric Citrate)-EAP
    Arm/Group Description Patients received either PhosLo (calcium acetate), Renvela (sevelamer carbonate), or a combination of these treatments during a 52-week Safety Assessment Period. Patients received KRX-0502 (ferric citrate) during a 52-week Safety Assessment Period. Patients that completed the 52-week Safety Assessment Period were randomized to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period. Patients that completed the 52-week Safety Assessment Period on KRX-0502 were randomized 1:1 to continue to receive KRX-0502 (ferric citrate) or placebo for a 4-week Efficacy Assessment Period.
    Measure Participants 141 273 0 0
    Median (Full Range) [Units/Day]
    993.46
    755.80
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Active Control-SAP, KRX-0502 (Ferric Citrate)-SAP
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments

    Adverse Events

    Time Frame Serious treatement emergent adverse events (TEAEs) up to 56 weeks
    Adverse Event Reporting Description Safety Population, includes all patients that took at least 1 dose of study drug
    Arm/Group Title KRX-0502 (SAP) Active Control (SAP) KRX-0502 (EAP) Placebo (EAP)
    Arm/Group Description Safety Assessment Period (Week 1-52) Safety Assessment Period (Week 1-52) Efficacy Assessment Period (Week 52-56) Efficacy Assessment Period (Week 52-56)
    All Cause Mortality
    KRX-0502 (SAP) Active Control (SAP) KRX-0502 (EAP) Placebo (EAP)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    KRX-0502 (SAP) Active Control (SAP) KRX-0502 (EAP) Placebo (EAP)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 114/289 (39.4%) 73/149 (49%) 11/95 (11.6%) 17/95 (17.9%)
    Blood and lymphatic system disorders
    Anemia 4/289 (1.4%) 4 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Graft thrombosis 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Iron deficiency anemia 1/289 (0.3%) 1 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Sepsis 5/289 (1.7%) 5 8/149 (5.4%) 8 0/95 (0%) 0 1/95 (1.1%) 1
    Disseminated Intravascular Coagulation 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Leukocytosis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Lymphadenopathy 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Thrombocytopenia 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Cardiac disorders
    Acute coronary syndrome 1/289 (0.3%) 1 2/149 (1.3%) 2 1/95 (1.1%) 1 0/95 (0%) 0
    Acute myocardial infarction 1/289 (0.3%) 1 4/149 (2.7%) 4 0/95 (0%) 0 0/95 (0%) 0
    Aortic stenosis 0/289 (0%) 0 2/149 (1.3%) 2 1/95 (1.1%) 1 0/95 (0%) 0
    Atrial fibrillation 4/289 (1.4%) 4 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Cardiac arrest 3/289 (1%) 3 2/149 (1.3%) 2 1/95 (1.1%) 1 0/95 (0%) 0
    Cardiac failure congestive 1/289 (0.3%) 1 3/149 (2%) 3 0/95 (0%) 0 0/95 (0%) 0
    Chest discomfort 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Chest pain 8/289 (2.8%) 8 5/149 (3.4%) 5 2/95 (2.1%) 2 1/95 (1.1%) 1
    Coronary artery disease 1/289 (0.3%) 1 3/149 (2%) 3 1/95 (1.1%) 1 0/95 (0%) 0
    Dyspnea 1/289 (0.3%) 1 3/149 (2%) 3 0/95 (0%) 0 0/95 (0%) 0
    Hypertensive crisis 3/289 (1%) 3 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Hypertensive emergency 3/289 (1%) 3 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Myocardial infarction 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Orthostatic hypotension 3/289 (1%) 3 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Sudden death 2/289 (0.7%) 2 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Atrial Thrombosis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Diastolic Dysfunction 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Sinus Tachycardia 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Angina Pectoris 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Angina Unstable 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Arrhythmia 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Cardiac Failure 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Cardiac Failure Acute 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Cardiac Tamponade 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Cardio-Respiratory Arrest 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Pericardial Effusion 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Tachycardia 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Ventricular Fibrillation 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Endocarditis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    atrial flutter 0/289 (0%) 0 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Mitral Valve Incompetence 0/289 (0%) 0 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Ear and labyrinth disorders
    Vertigo 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Vertigo Positional 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Eye disorders
    Retinopathy Hypertensive 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Gastrointestinal disorders
    Abdominal pain 4/289 (1.4%) 4 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Constipation 2/289 (0.7%) 2 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Diarrhea 2/289 (0.7%) 2 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Gastroenteritis 0/289 (0%) 0 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Gastrointestinal hemorrhage 5/289 (1.7%) 5 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Ileitis 0/289 (0%) 0 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Impaired gastric emptying 1/289 (0.3%) 1 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Nausea 3/289 (1%) 3 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Pancreatitis 2/289 (0.7%) 2 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Pancreatitis acute 0/289 (0%) 0 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Rectal hemorrhage 0/289 (0%) 0 3/149 (2%) 3 0/95 (0%) 0 0/95 (0%) 0
    Vomiting 2/289 (0.7%) 2 4/149 (2.7%) 4 0/95 (0%) 0 0/95 (0%) 0
    Colitis 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Duodenitis 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Small Intestinal Obstruction 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Abdominal Pain Upper 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Ascites 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Gastritis Erosive 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Haematemesis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Lower Gastrointestinal Haemorrhage 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Oesophagitis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Retroperitoneal Haematoma 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Swollen Tongue 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Upper Gastrointestinal Haemorrhage 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Gastroenteritis Viral 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Gastrointestinal Viral Infection 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    General disorders
    Asthenia 3/289 (1%) 3 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Fluid Overload 5/289 (1.7%) 5 5/149 (3.4%) 5 0/95 (0%) 0 0/95 (0%) 0
    Hyperkalemia 4/289 (1.4%) 4 2/149 (1.3%) 2 0/95 (0%) 0 1/95 (1.1%) 1
    Hypokalemia 3/289 (1%) 3 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Non-cardiac chest pain 0/289 (0%) 0 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Pyrexia 4/289 (1.4%) 4 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Adverse Event 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Device Occlusion 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Hernia Obstructive 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Oedema 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Acute Hepatic Failure 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Cholecystitis Acute 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Cholelithiasis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Hepatic Cirrhosis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Immune system disorders
    Anaphylactic Reaction 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Infections and infestations
    Bacteremia 1/289 (0.3%) 1 3/149 (2%) 3 0/95 (0%) 0 2/95 (2.1%) 2
    Cellulitis 1/289 (0.3%) 1 2/149 (1.3%) 2 0/95 (0%) 0 1/95 (1.1%) 1
    Clostridium difficile colitis 0/289 (0%) 0 2/149 (1.3%) 2 0/95 (0%) 0 1/95 (1.1%) 1
    Device related infection 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Gangrene 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Osteomyelitis 3/289 (1%) 3 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Peritonitis 2/289 (0.7%) 2 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Urinary tract infection 4/289 (1.4%) 4 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Wound infection 3/289 (1%) 3 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Lobar Pneumonia 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Staphylococcal Bacteraemia 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Staphylococcal Infection 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Viral Infection 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Abscess 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Anal Abscess 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Appendicitis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Arteriovenous Graft Site Infection 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Breast Abscess 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Catheter Site Cellulitis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Catheter Site Infection 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Clostridial Infection 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Diabetic Foot Infection 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Diverticulitis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Enterococcal Sepsis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Gastroenteritis Viral 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Graft Infection 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Localised Infection 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Oesophageal Candidiasis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Pelvic Abscess 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Postoperative Wound Infection 1/289 (0.3%) 1 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Tooth Abscess 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Viral Upper Respiratory Tract Infection 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Bronchitis 0/289 (0%) 0 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Injury, poisoning and procedural complications
    Hip Fracture 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Vascular Graft Complication 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Arteriovenous Fistula Site Complication 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Arteriovenous Fistula Site Haemorrhage 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Fall 1/289 (0.3%) 1 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Fibula Fracture 0/289 (0%) 0 1/149 (0.7%) 1 1/95 (1.1%) 1 0/95 (0%) 0
    Post Procedural Haematoma 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Post Procedural Haemorrhage 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Postoperative Wound Complication 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Procedural Hypertension 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Procedural Pain 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Spinal Compression Fracture 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Subdural Haematoma 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Tibia Fracture 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Vascular Graft Thrombosis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Wound 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Graft Infection 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Ankle Fracture 0/289 (0%) 0 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Rib Fracture 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Investigations
    Alanine Aminotransferase Increased 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Aspartate Aminotransferase Increased 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Blood Glucose Decreased 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Catheterisation Cardiac 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Electrocardiogram Qt Prolonged 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Heart Rate Increased 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    International Normalised Ratio Increased 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Liver Function Test Abnormal 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Troponin I Increased 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Troponin Increased 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Metabolism and nutrition disorders
    Hypoglycemia 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Hyperglycaemia 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Decreased Appetite 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Diabetic Ketoacidosis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Back Pain 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Chondrocalcinosis Pyrophosphate 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Fistula 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Intervertebral Disc Degeneration 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Joint Effusion 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Joint Swelling 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Muscular Weakness 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 1/95 (1.1%) 1
    Musculoskeletal Pain 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Pain In Extremity 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Spinal Column Stenosis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gallbladder Cancer Metastatic 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Metastatic Neoplasm 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Oesophageal Neoplasm 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Lymphoma 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Neoplasm Malignant 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Renal Cyst Infection 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Prostate Cancer 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Hepatobiliary Disorders 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Nervous system disorders
    Syncope 4/289 (1.4%) 4 2/149 (1.3%) 2 0/95 (0%) 0 0/95 (0%) 0
    Transient ischemic attack 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Cerebrovascular Accident 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 1/95 (1.1%) 1
    Cerebral Haemorrhage 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Aphasia 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Brain Oedema 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Brain Stem Haemorrhage 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Cerebral Infarction 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Convulsion 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Encephalopathy 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Hemiparesis 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Ischaemic Cerebral Infarction 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Lumbar Radiculopathy 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Myoclonus 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Quadriplegia 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Hepatic Cancer Metastatic 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Haemorrhagic Stroke 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Loss of Consciousness 0/289 (0%) 0 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Psychiatric Disorders 0/289 (0%) 0 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Psychiatric disorders
    Confusional state 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Mental disorder 3/289 (1%) 3 2/149 (1.3%) 2 1/95 (1.1%) 1 0/95 (0%) 0
    Depression 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Anxiety 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Mental Status Changes 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Suicide Attempt 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Renal and urinary disorders
    Renal failure chronic 1/289 (0.3%) 1 2/149 (1.3%) 2 1/95 (1.1%) 1 0/95 (0%) 0
    Renal Failure Acute 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Renal Mass 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Urethral Obstruction 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Reproductive system and breast disorders
    Vaginal Haemorrhage 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary edema 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Chronic obstructive pulmonary disease 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Cough 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Dyspnea 2/289 (0.7%) 2 4/149 (2.7%) 4 0/95 (0%) 0 0/95 (0%) 0
    Hypoxia 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Pleural effusion 3/289 (1%) 3 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Pneumonia 8/289 (2.8%) 8 4/149 (2.7%) 4 0/95 (0%) 0 1/95 (1.1%) 1
    Pulmonary edema 2/289 (0.7%) 2 3/149 (2%) 3 0/95 (0%) 0 1/95 (1.1%) 1
    Pulmonary embolism 2/289 (0.7%) 2 3/149 (2%) 3 0/95 (0%) 0 0/95 (0%) 0
    Respiratory failure 3/289 (1%) 3 3/149 (2%) 3 0/95 (0%) 0 0/95 (0%) 0
    Acute Respiratory Failure 1/289 (0.3%) 1 1/149 (0.7%) 1 0/95 (0%) 0 1/95 (1.1%) 1
    Asthma 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Dyspnoea Exertional 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Pulmonary Mass 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Respiratory Distress 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Pneumonia Aspiration 0/289 (0%) 0 0/149 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0
    Skin and subcutaneous tissue disorders
    Skin ulcer 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Penile Ulceration 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Angioedema 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Surgical and medical procedures
    Arteriovenous graft 2/289 (0.7%) 2 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Leg amputation 2/289 (0.7%) 2 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Renal transplant 13/289 (4.5%) 13 5/149 (3.4%) 5 1/95 (1.1%) 1 0/95 (0%) 0
    Arterial Bypass Operation 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Arteriovenous Fistula Operation 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Coronary Angioplasty 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Coronary Artery Bypass 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Debridement 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Pancreas Transplant 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Parathyroidectomy 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Renal And Pancreas Transplant 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Stent Placement 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Surgery 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Metabolism And Nutrition Disorders 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Vascular disorders
    Deep vein thrombosis 1/289 (0.3%) 1 3/149 (2%) 3 0/95 (0%) 0 1/95 (1.1%) 1
    Hypertension 5/289 (1.7%) 5 5/149 (3.4%) 5 1/95 (1.1%) 1 1/95 (1.1%) 1
    Hypotension 6/289 (2.1%) 6 4/149 (2.7%) 4 1/95 (1.1%) 1 0/95 (0%) 0
    Vascular access complication 2/289 (0.7%) 2 3/149 (2%) 3 1/95 (1.1%) 1 0/95 (0%) 0
    Arteriosclerosis 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Arteriovenous Fistula 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Haematoma 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Hypovolaemic Shock 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Ischaemia 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Malignant Hypertension 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Necrosis Ischaemic 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Peripheral Ischaemia 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Peripheral Vascular Disorder 1/289 (0.3%) 1 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Steal Syndrome 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Subclavian Artery Occlusion 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 1/95 (1.1%) 1
    Septic Shock 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Dizziness 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Haemorrhoids 0/289 (0%) 0 1/149 (0.7%) 1 0/95 (0%) 0 0/95 (0%) 0
    Haemorrhage 0/289 (0%) 0 0/149 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1
    Other (Not Including Serious) Adverse Events
    KRX-0502 (SAP) Active Control (SAP) KRX-0502 (EAP) Placebo (EAP)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 211/289 (73%) 88/149 (59.1%) 5/95 (5.3%) 0/95 (0%)
    Cardiac disorders
    Dyspnea 10/289 (3.5%) 10 11/149 (7.4%) 11 0/95 (0%) 0 0/95 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 14/289 (4.8%) 14 7/149 (4.7%) 7 0/95 (0%) 0 0/95 (0%) 0
    Constipation 21/289 (7.3%) 21 6/149 (4%) 6 0/95 (0%) 0 0/95 (0%) 0
    Diarrhea 72/289 (24.9%) 72 19/149 (12.8%) 19 0/95 (0%) 0 0/95 (0%) 0
    Feces discolored 49/289 (17%) 49 0/149 (0%) 0 0/95 (0%) 0 0/95 (0%) 0
    Nausea 38/289 (13.1%) 38 18/149 (12.1%) 18 0/95 (0%) 0 0/95 (0%) 0
    Vomiting 24/289 (8.3%) 24 18/149 (12.1%) 18 0/95 (0%) 0 0/95 (0%) 0
    General disorders
    Chest pain 15/289 (5.2%) 15 6/149 (4%) 6 0/95 (0%) 0 0/95 (0%) 0
    Edema peripheral 9/289 (3.1%) 9 8/149 (5.4%) 8 0/95 (0%) 0 0/95 (0%) 0
    Pyrexia 9/289 (3.1%) 9 7/149 (4.7%) 7 0/95 (0%) 0 0/95 (0%) 0
    Infections and infestations
    Nasopharyngitis 21/289 (7.3%) 21 9/149 (6%) 9 0/95 (0%) 0 0/95 (0%) 0
    Injury, poisoning and procedural complications
    Arteriovenous fistula site complication 12/289 (4.2%) 12 8/149 (5.4%) 8 0/95 (0%) 0 0/95 (0%) 0
    Vascular access complication 23/289 (8%) 23 14/149 (9.4%) 14 5/95 (5.3%) 5 0/95 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 15/289 (5.2%) 15 5/149 (3.4%) 5 0/95 (0%) 0 0/95 (0%) 0
    Hyperkalemia 8/289 (2.8%) 8 9/149 (6%) 9 0/95 (0%) 0 0/95 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 7/289 (2.4%) 7 7/149 (4.7%) 7 0/95 (0%) 0 0/95 (0%) 0
    Pain in extremity 15/289 (5.2%) 15 14/149 (9.4%) 14 0/95 (0%) 0 0/95 (0%) 0
    Nervous system disorders
    Dizziness 14/289 (4.8%) 14 10/149 (6.7%) 10 0/95 (0%) 0 0/95 (0%) 0
    Headache 22/289 (7.6%) 22 11/149 (7.4%) 11 0/95 (0%) 0 0/95 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 26/289 (9%) 26 15/149 (10.1%) 15 0/95 (0%) 0 0/95 (0%) 0
    Dyspnea 12/289 (4.2%) 12 7/149 (4.7%) 7 0/95 (0%) 0 0/95 (0%) 0
    Hypotension 15/289 (5.2%) 15 12/149 (8.1%) 12 0/95 (0%) 0 0/95 (0%) 0
    Skin and subcutaneous tissue disorders
    Pruritus 14/289 (4.8%) 14 10/149 (6.7%) 10 0/95 (0%) 0 0/95 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Medical Information
    Organization Keryx Biopharmaceuticals Inc
    Phone 1-844-44-KERYX (1-844-445-3799
    Email medicalinfo@keryx.com
    Responsible Party:
    Keryx Biopharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01191255
    Other Study ID Numbers:
    • KRX-0502-304
    • NCT01510106
    First Posted:
    Aug 30, 2010
    Last Update Posted:
    Dec 10, 2014
    Last Verified:
    Dec 1, 2014