Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)

Sponsor
Akebia Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT02680574
Collaborator
(none)
1,725
503
2
53.9
3.4
0.1

Study Details

Study Description

Brief Summary

A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance treatment of anemia in participants with Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of Vadadustat versus Darbepoetin alfa for the maintenance treatment of anemia in participants with NDD-CKD

Study Design

Study Type:
Interventional
Actual Enrollment :
1725 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
Sponsor was blinded during the study
Primary Purpose:
Treatment
Official Title:
Phase 3, Randomized, Open-label, Active-controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Maintenance Treatment of Anemia in Subjects With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD) (PRO2TECT-CONVERSION)
Actual Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Jun 18, 2020
Actual Study Completion Date :
Jul 31, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Vadadustat

Drug: Vadadustat
Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
Other Names:
  • AKB-6548
  • Active Comparator: Darbepoetin alfa

    Drug: Darbepoetin alfa
    Subcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Other Names:
  • Aranesp
  • Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) [Baseline; Weeks 24 to 36]

      The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates.

    2. Median Time to First Major Adverse Cardiovascular Event (MACE) [Up to Week 208]

      MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    Secondary Outcome Measures

    1. Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52) [Baseline; Weeks 40 to 52]

      The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates.

    2. Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis [Up to Week 208]

      MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    3. Median Time to First Cardiovascular MACE [Up to Week 208]

      MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    4. Median Time to First Cardiovascular Death [Up to Week 208]

      Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    5. Median Time to First All-cause Mortality [Up to Week 208]

      Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    Other Outcome Measures

    1. Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) [Weeks 24 to 36]

    2. Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) [Weeks 24 to 36]

    3. Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) [Weeks 40 to 52]

    4. Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) [Weeks 40 to 52]

    5. Exploratory - Proportion of Participants With an Hb Increase of >1.0 g/dL From Baseline Visit [Baseline; up to Week 52]

    6. Exploratory - Time to Achieve Hb Increase of >1.0 g/dL From Baseline Visit [Baseline; up to Week 52]

    7. Exploratory - Mean Change in Hb Between Baseline (Mean Pretreatment Hb) and the Primary Evaluation Period (Mean Hb From Weeks 24 to 36) Stratified by Pre-baseline Erythropoiesis-stimulating Agent (ESA) Exposure [Baseline; Weeks 24 to 36]

    8. Exploratory - Mean Monthly Dose of Intravenous (IV) Elemental Iron Administered in Participants Who Have Received IV Iron [Up to Week 52]

    9. Exploratory - Proportion of Participants Receiving IV Iron Therapy [Up to Week 52]

    10. Exploratory - Proportion of Participants Receiving Red Blood Cells (RBCs) Transfusion(s) [Up to Week 52]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • ≥18 years of age

    • Diagnosis of chronic kidney disease (CKD) with an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) at Screening and not expected to start dialysis within 6 months of Screening

    • Currently maintained on erythropoiesis-stimulating agents therapy, with a dose received within 6 weeks prior to or during Screening

    • Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States (US) and between 9.0 and 12.0 g/dL (inclusive) outside of the US

    • Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening

    Exclusion Criteria:
    • Anemia due to a cause other than CKD or participant with active bleeding or recent blood loss

    • Red blood cell transfusion within 8 weeks prior to randomization

    • Uncontrolled hypertension

    • Severe heart failure at Screening (New York Heart Association Class IV)

    • Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular, or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure, or stroke within 12 weeks prior to or during Screening

    • Hypersensitivity to Darbepoetin or Vadadustat or to any of their excipients

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Birmingham Alabama United States 35211
    2 Research Site Huntsville Alabama United States 35805
    3 Research Site Tuscumbia Alabama United States 35674
    4 Research Site Glendale Arizona United States 85306
    5 Research Site Mesa Arizona United States 85210
    6 Research Site Phoenix Arizona United States 85027
    7 Research Site Tucson Arizona United States 85718
    8 Research Site Tucson Arizona United States 85724
    9 Research Site Anaheim California United States 92801
    10 Research Site Bakersfield California United States 93309
    11 Research Site #1 Chula Vista California United States 91910
    12 Research Site #2 Chula Vista California United States 91910
    13 Research Site El Centro California United States 92243
    14 Research Site Fountain Valley California United States 92708
    15 Research Site Glendale California United States 91206
    16 Research Site Granada Hills California United States 91344
    17 Research Site La Mesa California United States 91942
    18 Research Site Laguna Hills California United States 92653
    19 Research Site Long Beach California United States 90807
    20 Research Site Long Beach California United States 92886
    21 Research Site Los Angeles California United States 90048
    22 Research Site Lynwood California United States 90260
    23 Research Site #1 Northridge California United States 91324
    24 Research Site #2 Northridge California United States 91324
    25 Research Site Riverside California United States 92505
    26 Research Site Roseville California United States 95661
    27 Research Site Salinas California United States 93901
    28 Research Site San Diego California United States 92103-6204
    29 Research Site #1 San Dimas California United States 91773
    30 Research Site #2 San Dimas California United States 91773
    31 Research Site Santa Ana California United States 92704
    32 Research Site Santa Monica California United States 90404
    33 Research Site Sherman Oaks California United States 91403
    34 Research Site Thousand Oaks California United States 91360
    35 Research Site Whittier California United States 90603
    36 Research Site Whittier California United States 99999
    37 Research Site Arvada Colorado United States 80002
    38 Research Site Denver Colorado United States 80230
    39 Research Site Westminster Colorado United States 80031
    40 Research Site Stamford Connecticut United States 06902
    41 Research Site Waterbury Connecticut United States 06708
    42 Research Site Bradenton Florida United States 34209
    43 Research Site Brandon Florida United States 33511
    44 Research Site Cooper City Florida United States 33024
    45 Research Site #1 Coral Gables Florida United States 33134
    46 Research Site #2 Coral Gables Florida United States 33134
    47 Research Site Coral Springs Florida United States 33065
    48 Research Site Coral Springs Florida United States 33071
    49 Research Site Doral Florida United States 33166
    50 Research Site Edgewater Florida United States 32132
    51 Research Site Hialeah Florida United States 33010
    52 Research Site #1 Hialeah Florida United States 33012
    53 Research Site #2 Hialeah Florida United States 33012
    54 Research Site #3 Hialeah Florida United States 33012
    55 Research Site Hialeah Florida United States 33018
    56 Research Site #1 Hollywood Florida United States 33024
    57 Research Site #2 Hollywood Florida United States 33024
    58 Research Site Jacksonville Florida United States 32204
    59 Research Site #1 Jacksonville Florida United States 32216
    60 Research Site #2 Jacksonville Florida United States 32216
    61 Research Site Lake Worth Florida United States 33467
    62 Research Site Lauderdale Lakes Florida United States 33313
    63 Research Site Miami Beach Florida United States 33140
    64 Research Site Miami Lakes Florida United States 33014
    65 Research Site #1 Miami Lakes Florida United States 33016
    66 Research Site #2 Miami Lakes Florida United States 33016
    67 Research Site Miami Florida United States 33122
    68 Research Site Miami Florida United States 33125-4141
    69 Research Site #1 Miami Florida United States 33126
    70 Research Site #2 Miami Florida United States 33126
    71 Research Site Miami Florida United States 33133
    72 Research Site Miami Florida United States 33134
    73 Research Site Miami Florida United States 33135
    74 Research Site Miami Florida United States 33143
    75 Research Site #1 Miami Florida United States 33144
    76 Research Site #2 Miami Florida United States 33144
    77 Research Site Miami Florida United States 33145
    78 Research Site Miami Florida United States 33150
    79 Research Site Miami Florida United States 33157
    80 Research Site Miami Florida United States 33165
    81 Research Site Miami Florida United States 33169
    82 Research Site Miami Florida United States 33173
    83 Research Site #1 Miami Florida United States 33175
    84 Research Site #2 Miami Florida United States 33175
    85 Research Site Pembroke Pines Florida United States 33026
    86 Research Site Pompano Beach Florida United States 33060
    87 Research Site Port Charlotte Florida United States 33952
    88 Research Site Tampa Florida United States 33604
    89 Research Site Tampa Florida United States 33612
    90 Research Site Tampa Florida United States 33614
    91 Research Site Atlanta Georgia United States 30338
    92 Research Site Atlanta Georgia United States 30342
    93 Research Site Atlanta Georgia United States 30350
    94 Research Site Augusta Georgia United States 30909
    95 Research Site Columbus Georgia United States 31901
    96 Research Site #1 Columbus Georgia United States 31904
    97 Research Site #2 Columbus Georgia United States 31904
    98 Research Site #1 Lawrenceville Georgia United States 30046
    99 Research Site #2 Lawrenceville Georgia United States 30046
    100 Research Site Macon Georgia United States 31217
    101 Research Site Meridian Idaho United States 83642
    102 Research Site Chicago Illinois United States 60637
    103 Research Site Elk Grove Village Illinois United States 60007
    104 Research Site Evanston Illinois United States 60201
    105 Research Site McHenry Illinois United States 60050
    106 Research Site Peoria Illinois United States 61603
    107 Research Site Anderson Indiana United States 46011
    108 Research Site Fort Wayne Indiana United States 46804
    109 Research Site Jeffersonville Indiana United States 47130
    110 Research Site #1 Merrillville Indiana United States 46410
    111 Research Site #2 Merrillville Indiana United States 46410
    112 Research Site Michigan City Indiana United States 46360
    113 Research Site Muncie Indiana United States 47304
    114 Research Site Monroe Louisiana United States 71201
    115 Research Site New Orleans Louisiana United States 70115
    116 Research Site Shreveport Louisiana United States 71101
    117 Research Site Shreveport Louisiana United States 71103
    118 Research Site Portland Maine United States 04102
    119 Research Site Baltimore Maryland United States 21218
    120 Research Site Greenbelt Maryland United States 20770
    121 Research Site Takoma Park Maryland United States 20912
    122 Research Site Methuen Massachusetts United States 01844
    123 Research Site Plymouth Massachusetts United States 02360
    124 Research Site Springfield Massachusetts United States 01107
    125 Research Site Detroit Michigan United States 48202
    126 Research Site Pontiac Michigan United States 48341
    127 Research Site Port Huron Michigan United States 91344
    128 Research Site Roseville Michigan United States 48066
    129 Research Site Minneapolis Minnesota United States 55404
    130 Research Site Saint Paul Minnesota United States 55102
    131 Research Site Gulfport Mississippi United States 39501
    132 Research Site Columbia Missouri United States 65201
    133 Research Site Kansas City Missouri United States 64111
    134 Research Site Kansas City Missouri United States 64128
    135 Research Site Butte Montana United States 59701
    136 Research Site Lincoln Nebraska United States 68510
    137 Research Site Omaha Nebraska United States 68124
    138 Research Site #1 Las Vegas Nevada United States 89106
    139 Research Site #2 Las Vegas Nevada United States 89106
    140 Research Site Portsmouth New Hampshire United States 03801
    141 Research Site Berlin New Jersey United States 08009
    142 Research Site Voorhees New Jersey United States 08043
    143 Research Site Albuquerque New Mexico United States 87106
    144 Research Site Albuquerque New Mexico United States 87108
    145 Research Site Albuquerque New Mexico United States 87109
    146 Research Site Santa Fe New Mexico United States 87505
    147 Research Site Bronx New York United States 10467
    148 Research Site Flushing New York United States 11355
    149 Research Site Laurelton New York United States 11413
    150 Research Site Mineola New York United States 11501
    151 Research Site New York New York United States 10010
    152 Research Site Asheville North Carolina United States 28801
    153 Research Site #1 Greenville North Carolina United States 27834
    154 Research Site #2 Greenville North Carolina United States 27834
    155 Research Site Jacksonville North Carolina United States 28546
    156 Research Site Kinston North Carolina United States 28504
    157 Research Site Morehead City North Carolina United States 28557
    158 Research Site New Bern North Carolina United States 28560
    159 Research Site Wilmington North Carolina United States 28401
    160 Research Site Winston-Salem North Carolina United States 27103
    161 Research Site Akron Ohio United States 44302
    162 Research Site Columbus Ohio United States 43203
    163 Research Site Marion Ohio United States 43302
    164 Research Site Maumee Ohio United States 43537
    165 Research Site Portland Oregon United States 97216
    166 Research Site Doylestown Pennsylvania United States 18901
    167 Research Site Jersey Shore Pennsylvania United States 17740
    168 Research Site Philadelphia Pennsylvania United States 19140
    169 Research Site East Providence Rhode Island United States 02915
    170 Research Site Providence Rhode Island United States 02908
    171 Research Site Anderson South Carolina United States 29625
    172 Research Site Columbia South Carolina United States 29203
    173 Research Site Orangeburg South Carolina United States 29118
    174 Research Site Sumter South Carolina United States 29150-1900
    175 Research Site West Columbia South Carolina United States 29169
    176 Research Site Chattanooga Tennessee United States 37408
    177 Research Site Knoxville Tennessee United States 37923
    178 Research Site Memphis Tennessee United States 38104
    179 Research Site Nashville Tennessee United States 37205
    180 Research Site Arlington Texas United States 76015
    181 Research Site Dallas Texas United States 75220
    182 Research Site Dallas Texas United States 75390
    183 Research Site DeSoto Texas United States 75115
    184 Research Site El Paso Texas United States 79935
    185 Research Site Fort Worth Texas United States 76104
    186 Research Site Gonzales Texas United States 78629
    187 Research Site Greenville Texas United States 75401
    188 Research Site Greenville Texas United States 75402
    189 Research Site Houston Texas United States 33143
    190 Research Site #1 Houston Texas United States 77004
    191 Research Site #2 Houston Texas United States 77004
    192 Research Site Houston Texas United States 77054
    193 Research Site Lewisville Texas United States 75057
    194 Research Site #1 McAllen Texas United States 78503
    195 Research Site #2 McAllen Texas United States 78503
    196 Research Site McKinney Texas United States 75069
    197 Research Site McKinney Texas United States 75071
    198 Research Site Plano Texas United States 75024-5327
    199 Research Site San Antonio Texas United States 78207
    200 Research Site San Antonio Texas United States 78212-4740
    201 Research Site San Antonio Texas United States 78224
    202 Research Site San Antonio Texas United States 78240-1501
    203 Research Site Sherman Texas United States 75090
    204 Research Site Victoria Texas United States 77901
    205 Research Site Clinton Utah United States 84015
    206 Research Site Saint George Utah United States 84790
    207 Research Site Salt Lake City Utah United States 84115
    208 Research Site Burlington Vermont United States 05401
    209 Research Site Alexandria Virginia United States 22304
    210 Research Site Arlington Virginia United States 22207
    211 Research Site Danville Virginia United States 24541
    212 Research Site Hampton Virginia United States 23666
    213 Research Site Lansdowne Town Center Virginia United States 20176
    214 Research Site Norfolk Virginia United States 23507
    215 Research Site Salem Virginia United States 24153
    216 Research Site Woodbridge Virginia United States 22191
    217 Research Site Tacoma Washington United States 98405
    218 Research Site Wenatchee Washington United States 98801
    219 Research Site Madison Wisconsin United States 53705
    220 Research Site Bahia Blanca Buenos Aires Argentina B8001HXM
    221 Research Site Junin Buenos Aires Argentina 6000
    222 Research Site Junin Buenos Aires Argentina B6000BHA
    223 Research Site Mar del Plata Buenos Aires Argentina B7600FYK
    224 Research Site Mar del Plata Buenos Aires Argentina B7600FZ
    225 Research Site Mar del Plata Buenos Aires Argentina B7602DCK
    226 Research Site Pergamino Buenos Aires Argentina B2700CPM
    227 Research Site Ramos Mejia Buenos Aires Argentina B1704ETD
    228 Research Site San Miguel Buenos Aires Argentina B1663CNJ
    229 Research Site San Nicolas Buenos Aires Argentina B2900DMH
    230 Research Site Sarandi Buenos Aires Argentina B1872EEA
    231 Research Site Temperley Buenos Aires Argentina 1834
    232 Research Site Godoy Cruz Mendoza Argentina 5501
    233 Research Site Rosario Santa Fe Argentina S2000DIF
    234 Research Site Rosario Santa Fe Argentina S2000DNM
    235 Research Site San Miguel de Tucuman Tucuman Argentina 4000
    236 Research Site San Miguel de Tucuman Tucuman Argentina T4000AXL
    237 Research Site San Miguel de Tucuman Tucuman Argentina T4000ICL
    238 Research Site San Miguel de Tucuman Tucuman Argentina T4000
    239 Research Site Ciudad Autonoma Buenos Aires Argentina C1093AAS
    240 Research Site Ciudad Autonoma Buenos Aires Argentina C1430CKE
    241 Research Site Cordoba Argentina 5000
    242 Research Site Cordoba Argentina X5000AAW
    243 Research Site Cordoba Argentina X5000EVQ
    244 Research Site Cordoba Argentina X5020AAA
    245 Research Site Corrientes Argentina 3400
    246 Research Site Salta Argentina 4406
    247 Research Site San Luis Argentina 5700
    248 Research Site Camperdown New South Wales Australia 2050
    249 Research Site Liverpool New South Wales Australia 2170
    250 Research Site Westmead New South Wales Australia 2145
    251 Research Site Cairns Queensland Australia 4870
    252 Research Site Gold Coast Queensland Australia 9726
    253 Research Site Adelaide South Australia Australia 5000
    254 Research Site Launceston Tasmania Australia 7250
    255 Research Site Bentleigh East Victoria Australia 3165
    256 Research Site Box Hill Victoria Australia 3128
    257 Research Site Fitzroy Victoria Australia 3065
    258 Research Site Nedlands Western Australia Australia 6009
    259 Research Site Perth Western Australia Australia 6000
    260 Research Site St. Pölten Austria 3100
    261 Research Site Wien Austria 1030
    262 Research Site Wien Austria 1220
    263 Research Site Feira de Santana Bahia Brazil 44001-584
    264 Research Site Itabuna Bahia Brazil 45600-625
    265 Research Site Salvador Bahia Brazil 40451-065
    266 Research Site Fortaleza Ceará Brazil 60115-282
    267 Research Site Fortaleza Ceará Brazil 60430-370
    268 Research Site Vitória Espírito Santo Brazil 29055-450
    269 Research Site Belo Horizonte Minas Gerais Brazil 30150-320
    270 Research Site Juiz de Fora Minas Gerais Brazil 36036-330
    271 Research Site Curitiba Paraná Brazil 80230-130
    272 Research Site #1 Curitiba Paraná Brazil 80810-040
    273 Research Site #2 Curitiba Paraná Brazil 80810-040
    274 Research Site Maringá Paraná Brazil 87060-040
    275 Research Site Rio de Janeiro Rio Do Janeiro Brazil 20551-030
    276 Research Site Caxias do Sul Rio Grande Do Sul Brazil 95010-005
    277 Research Site Porto Alegre Rio Grande Do Sul Brazil 90035-074
    278 Research Site Porto Alegre Rio Grande Do Sul Brazil 90035-903
    279 Research Site Porto Alegre Rio Grande Do Sul Brazil 90160-093
    280 Research Site Porto Alegre Rio Grande Do Sul Brazil 90610-000
    281 Research Site Criciúma Santa Catarina Brazil 88801-250
    282 Research Site Joinville Santa Catarina Brazil 89202-050
    283 Research Site Botucatu Sao Paulo Brazil 18618-970
    284 Research Site Campinas Sao Paulo Brazil 13087-567
    285 Research Site Santo André Sao Paulo Brazil 09080-110
    286 Research Site Santo André Sao Paulo Brazil 09090-790
    287 Research Site São Bernardo do Campo Sao Paulo Brazil 09715-090
    288 Research Site São Paulo Sao Paulo Brazil 01141-020
    289 Research Site São Paulo Sao Paulo Brazil 01406-200
    290 Research Site São Paulo Sao Paulo Brazil 04025-011
    291 Research Site São Paulo Sao Paulo Brazil 05403-000
    292 Research Site Byala Bulgaria 7100
    293 Research Site Cherven bryag Bulgaria 5980
    294 Research Site Lom Bulgaria 3600
    295 Research Site Silistra Bulgaria 7500
    296 Research Site Sliven Bulgaria 8800
    297 Research Site Smolyan Bulgaria 4700
    298 Research Site Sofia Bulgaria 1233
    299 Research Site Sofia Bulgaria 1407
    300 Research Site #1 Sofia Bulgaria 1431
    301 Research Site #2 Sofia Bulgaria 1431
    302 Research Site Sofia Bulgaria 1606
    303 Research Site Sofia Bulgaria 1784
    304 Research Site Stara Zagora Bulgaria 6000
    305 Research Site Varna Bulgaria 9000
    306 Research Site Varna Bulgaria 9002
    307 Research Site Veliko Tarnovo Bulgaria 5000
    308 Research Site Vratsa Bulgaria 3000
    309 Research Site Scarborough Ontario Canada M1H 3G4
    310 Research Site Concepción Chile 4030000
    311 Research Site Puerto Varas Chile 5550170
    312 Research Site Santiago Chile 8431657
    313 Research Site Temuco Chile 4780000
    314 Research Site Barranquilla Colombia 080020
    315 Research Site Bogota Colombia 110221
    316 Research Site Espinal Colombia 00000
    317 Research Site Manizales Colombia 170004
    318 Research Site #1 Medellin Colombia 050021
    319 Research Site #2 Medellin Colombia 050021
    320 Research Site Medellín Colombia 500515
    321 Research Site Ceske Budejovice Czechia 370 01
    322 Research Site Hradec Kralove Czechia 50333
    323 Research Site Praha 2 Czechia 128 08
    324 Research Site Praha 4 Czechia 140 21
    325 Research Site Lille Alpes De Haute Provence France 59000
    326 Research Site Saint-Priest-En-Jarez Loire France 42055
    327 Research Site Reims Cedex Marne France 51090
    328 Research Site Pontoise Val d'Oise France 95300
    329 Research Site Créteil Cedex Val De Marne France 94010
    330 Research Site Paris France 75015
    331 Research Site Paris France 75020
    332 Research Site Villingen-Schwenningen Baden Wuerttemberg Germany 78052
    333 Research Site Rostock Mecklenburg Vorpommern Germany 18057
    334 Research Site Duesseldorf Nordrhein Westfalen Germany 40210
    335 Research Site Berlin Germany 10117
    336 Research Site Berlin Germany 12627
    337 Research Site Hamburg Germany 22297
    338 Research Site #1 Baja Hungary 6500
    339 Research Site #2 Baja Hungary 6500
    340 Research Site Balatonfured Hungary 8230
    341 Research Site Budapest Hungary 1076
    342 Research Site Budapest Hungary 1145
    343 Research Site Debrecen Hungary 4032
    344 Research Site Esztergom Hungary 2500
    345 Research Site Hodmezovasarhely Hungary 6800
    346 Research Site Kalocsa Hungary 6300
    347 Research Site Kaposvar Hungary 7400
    348 Research Site Kecskemet Hungary 6000
    349 Research Site Kistarcsa Hungary 2143
    350 Research Site Pecs Hungary 7623
    351 Research Site Szeged Hungary 6720
    352 Research Site Szigetvar Hungary 7900
    353 Research Site Ashkelon Israel 78278
    354 Research Site Haifa Israel 3109601
    355 Research Site Nahariya Israel 2210001
    356 Research Site Ramat Gan Israel 52363
    357 Research Site Rishon Lezion Israel 75141
    358 Research Site Piedimonte Matese Caserta Italy 81016
    359 Research Site San Giovanni Rotondo Foggia Italy 71013
    360 Research Site Bari Italy 70124
    361 Research Site Lecco Italy 23900
    362 Research Site Milano Italy 20142
    363 Research Site Milano Italy 20162
    364 Research Site #1 Napoli Italy 80138
    365 Research Site #2 Napoli Italy 80138
    366 Research Site Parma Italy 43100
    367 Research Site Pavia Italy 27100
    368 Research Site Roma Italy 00168
    369 Research Site Siena Italy 53100
    370 Research Site Bucheon-si Gyeonggi-do Korea, Republic of 14647
    371 Research Site Goyang-si Gyeonggi-do Korea, Republic of 10380
    372 Research Site Guri-si Gyeonggi-do Korea, Republic of 11923
    373 Research Site Seongnam-si Gyeonggi-do Korea, Republic of 13620
    374 Research Site Busan Korea, Republic of 47392
    375 Research Site Busan Korea, Republic of 49201
    376 Research Site Daegu Korea, Republic of 41944
    377 Research Site Seoul Korea, Republic of 02841
    378 Research Site Seoul Korea, Republic of 03080
    379 Research Site Seoul Korea, Republic of 06591
    380 Research Site Seoul Korea, Republic of 07345
    381 Research Site Seoul Korea, Republic of 135-710
    382 Research Site Alor Setar Kedah Malaysia 05460
    383 Research Site Kuala Lumpur Malaysia 56000
    384 Research Site Kuala Lumpur Malaysia 59100
    385 Research Site Pulau Pinang Malaysia 10990
    386 Research Site Torreon Coahuila Mexico 27000
    387 Research Site Mexico Distrito Federal Mexico 06100
    388 Research Site Mexico Distrito Federal Mexico 06700
    389 Research Site Acapulco de Juarez Guerrero Mexico 39670
    390 Research Site #1 Pachuca Hidalgo Mexico 42070
    391 Research Site #2 Pachuca Hidalgo Mexico 42070
    392 Research Site Guadalajara Jalisco Mexico 44130
    393 Research Site Zapopan Jalisco Mexico 45030
    394 Research Site Zapopan Jalisco Mexico 45116
    395 Research Site Zapopan Jalisco Mexico 45200
    396 Research Site Morelia Michoacán Mexico 58260
    397 Research Site Monterrey Nuevo León Mexico 64620
    398 Research Site Monterrey Nuevo León Mexico 64710
    399 Research Site San Juan del Rio Queretaro Mexico 76800
    400 Research Site Culiacan Sinaloa Mexico 80200
    401 Research Site Culiacan Sinaloa Mexico 80230
    402 Research Site Culiacán Sinaloa Mexico 80030
    403 Research Site Mazatlan Sinaloa Mexico 82110
    404 Research Site Chihuahua Mexico 31203
    405 Research Site Chihuahua Mexico 31217
    406 Research Site Durango Mexico 34000
    407 Research Site Veracruz Mexico 91900
    408 Research Site Hamilton New Zealand 3200
    409 Research Site New Plymouth New Zealand 4342
    410 Research Site Nowa Sol Poland 67-100
    411 Research Site Caguas Puerto Rico 00725
    412 Research Site Bucuresti Romania 010719
    413 Research Site Bucuresti Romania 011794
    414 Research Site #1 Bucuresti Romania 022328
    415 Research Site #2 Bucuresti Romania 022328
    416 Research Site Bucuresti Romania 042122
    417 Research Site Oradea Romania 410469
    418 Research Site Timisoara Romania 300182
    419 Research Site Kazan Russian Federation 420012
    420 Research Site Kemerovo Russian Federation 650066
    421 Research Site Krasnoyarsk Russian Federation 660062
    422 Research Site Nizhniy Novgorod Russian Federation 603076
    423 Research Site Novosibirsk Russian Federation 630054
    424 Research Site Novosibirsk Russian Federation 630091
    425 Research Site Petrozavodsk Russian Federation 185019
    426 Research Site Pushkin Russian Federation 196603
    427 Research Site Saint-Petersburg Russian Federation 195271
    428 Research Site Saint-Petersburg Russian Federation 197022
    429 Research Site Yaroslavl Russian Federation 150062
    430 Research Site #1 Belgrade Serbia 11000
    431 Research Site #2 Belgrade Serbia 11000
    432 Research Site #3 Belgrade Serbia 11000
    433 Research Site Kragujevac Serbia 34000
    434 Research Site Lazarevac Serbia 11000
    435 Research Site Nis Serbia 18000
    436 Research Site Zajecar Serbia 19000
    437 Research Site Bardejov Slovakia 08501
    438 Research Site Bratislava Slovakia 83103
    439 Research Site Galanta Slovakia 924 22
    440 Research Site Svidnik Slovakia 08901
    441 Research Site Trstena Slovakia 02801
    442 Research Site Bloemfontein Free State South Africa 9301
    443 Research Site Brandfort Free State South Africa 9400
    444 Research Site Pretoria Gauteng South Africa 0002
    445 Research Site Pretoria Gauteng South Africa 1692
    446 Research Site Vereeniging Gauteng South Africa 1935
    447 Research Site #1 Durban KwaZulu-Natal South Africa 4001
    448 Research Site #2 Durban KwaZulu-Natal South Africa 4001
    449 Research Site Durban KwaZulu-Natal South Africa 4092
    450 Research Site Durban KwaZulu-Natal South Africa 4320
    451 Research Site Tongaat KwaZulu-Natal South Africa 4399
    452 Research Site Worcester Western Cape South Africa 6850
    453 Research Site Elche Alicante Spain 03293
    454 Research Site Torrevieja Alicante Spain 03186
    455 Research Site Palma de Mallorca Baleares Spain 07120
    456 Research Site L'Hospitalet de Llobregat Barcelona Spain 08907
    457 Research Site Malaga Málaga Spain 29010
    458 Research Site Almeria Spain 04007
    459 Research Site Almeria Spain 04009
    460 Research Site Badajoz Spain 06006
    461 Research Site Barcelona Spain 08003
    462 Research Site Barcelona Spain 08025
    463 Research Site Barcelona Spain 08035
    464 Research Site Madrid Spain 28007
    465 Research Site Madrid Spain 28040
    466 Research Site Madrid Spain 28041
    467 Research Site Pamplona Spain 31001
    468 Research Site Sevilla Spain 41013
    469 Research Site Sevilla Spain 41071
    470 Research Site Valencia Spain 46014
    471 Research Site Valencia Spain 46026
    472 Research Site Ankara Turkey 06100
    473 Research Site Erciyes Turkey 38039
    474 Research Site Istanbul Turkey 34098
    475 Research Site Istanbul Turkey 34722
    476 Research Site Kocaeli Turkey 41380
    477 Research Site Dnipro Ukraine 49005
    478 Research Site Ivano-Frankivsk Ukraine 76008
    479 Research Site Ivano-Frankivsk Ukraine 76018
    480 Research Site Kharkiv Ukraine 61037
    481 Research Site Kharkiv Ukraine 61039
    482 Research Site Kharkiv Ukraine 61103
    483 Research Site Kharkiv Ukraine 61157
    484 Research Site Kropyvnytskyi Ukraine 25006
    485 Research Site Kyiv Ukraine 02125
    486 Research Site Kyiv Ukraine 04050
    487 Research Site Lutsk Ukraine 43005
    488 Research Site Lviv Ukraine 79013
    489 Research Site Mykolaiv Ukraine 54058
    490 Research Site Odesa Ukraine 65025
    491 Research Site Vinnytsia Ukraine 21001
    492 Research Site Vinnytsia Ukraine 21005
    493 Research Site Vinnytsia Ukraine 21018
    494 Research Site Zaporizhzhia Ukraine 69118
    495 Research Site Exeter Devon United Kingdom EX2 5DW
    496 Research Site London Greater London United Kingdom E1 1BB
    497 Research Site London Greater London United Kingdom SE5 9RS
    498 Research Site Salford Greater Manchester United Kingdom M6 8HD
    499 Research Site Stevenage Hertfordshire United Kingdom SG1 4AB
    500 Research Site Leicester Leicestershire United Kingdom LE5 4PW
    501 Research Site King's Lynn Norfolk United Kingdom PE30 4ET
    502 Research Site Doncaster South Yorkshire United Kingdom DN2 5LT
    503 Research Site Swansea United Kingdom SA6 6NL

    Sponsors and Collaborators

    • Akebia Therapeutics

    Investigators

    • Study Director: Chief Medical Officer, Akebia Therapeutics Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Akebia Therapeutics
    ClinicalTrials.gov Identifier:
    NCT02680574
    Other Study ID Numbers:
    • AKB-6548-CI-0015
    • 2015-004774-14
    First Posted:
    Feb 11, 2016
    Last Update Posted:
    Jun 27, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Akebia Therapeutics
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 2961 participants were screened for entry into the study. Of these, 1725 participants were enrolled and randomized into the study.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Period Title: Overall Study
    STARTED 862 863
    COMPLETED 704 711
    NOT COMPLETED 158 152

    Baseline Characteristics

    Arm/Group Title Vadadustat Darbepoetin Alfa Total
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. Total of all reporting groups
    Overall Participants 862 863 1725
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    67.3
    (13.14)
    66.5
    (13.52)
    66.9
    (13.33)
    Sex: Female, Male (Count of Participants)
    Female
    468
    54.3%
    488
    56.5%
    956
    55.4%
    Male
    394
    45.7%
    375
    43.5%
    769
    44.6%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    32
    3.7%
    26
    3%
    58
    3.4%
    Asian
    62
    7.2%
    55
    6.4%
    117
    6.8%
    Black or African American
    93
    10.8%
    131
    15.2%
    224
    13%
    Native Hawaiian or Other Pacific Islander
    3
    0.3%
    0
    0%
    3
    0.2%
    White
    631
    73.2%
    603
    69.9%
    1234
    71.5%
    Not Reported
    15
    1.7%
    13
    1.5%
    28
    1.6%
    Reported as Other
    25
    2.9%
    32
    3.7%
    57
    3.3%
    Multiple
    1
    0.1%
    3
    0.3%
    4
    0.2%
    Average hemoglobin (Grams per deciliter (g/dL)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Grams per deciliter (g/dL)]
    10.423
    (0.8871)
    10.390
    (0.9430)
    10.406
    (0.9154)
    Mean estimated glomerular filtration rate (mL/min/1.73m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mL/min/1.73m^2]
    22.6
    (11.64)
    22.8
    (12.04)
    22.7
    (11.84)
    Number of Participants with History of Diabetes (Count of Participants)
    Count of Participants [Participants]
    444
    51.5%
    432
    50.1%
    876
    50.8%
    Number of Participants with NYHA Functional Classification of Heart Failure (Count of Participants)
    NYHA Class 0
    610
    70.8%
    595
    68.9%
    1205
    69.9%
    NYHA Class I
    108
    12.5%
    108
    12.5%
    216
    12.5%
    NYHA Class II
    113
    13.1%
    122
    14.1%
    235
    13.6%
    NYHA Class III
    29
    3.4%
    36
    4.2%
    65
    3.8%
    NYHA Class IV
    0
    0%
    0
    0%
    0
    0%
    NYHA Class Missing
    2
    0.2%
    2
    0.2%
    4
    0.2%
    Number of Participants with Any History of Heart Failure (Count of Participants)
    Yes
    44
    5.1%
    52
    6%
    96
    5.6%
    No
    613
    71.1%
    595
    68.9%
    1208
    70%
    Missing
    205
    23.8%
    216
    25%
    421
    24.4%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
    Description The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates.
    Time Frame Baseline; Weeks 24 to 36

    Outcome Measure Data

    Analysis Population Description
    Randomized Population: All participants randomized. Analyses of this population were based on the randomized treatment.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Measure Participants 862 863
    Least Squares Mean (Standard Error) [Grams per deciliter (g/dL)]
    0.41
    (0.036)
    0.42
    (0.037)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments Treatment comparison: Vadadustat minus Darbepoetin Alfa
    Type of Statistical Test Non-Inferiority
    Comments Establishment of non-inferiority was based on a margin of -0.75 g/dL applied to the difference in mean change of hemoglobin: Vadadustat minus Darbepoetin alfa
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least squares mean difference
    Estimated Value -0.01
    Confidence Interval (2-Sided) 95%
    -0.09 to 0.07
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.042
    Estimation Comments
    2. Primary Outcome
    Title Median Time to First Major Adverse Cardiovascular Event (MACE)
    Description MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
    Time Frame Up to Week 208

    Outcome Measure Data

    Analysis Population Description
    Safety Population (PRO2TECT): All participants from the PRO2TECT (Non-dialysis-dependent chronic kidney disease [NDD-CKD]) population who received 1 or more doses of study drug. Only those participants with MACE events were analyzed for this outcome measure.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Measure Participants 168 152
    Median (Inter-Quartile Range) [Weeks]
    53.21
    58.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments Statistical analysis from study AKB-6548-CI-0015 has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per Food and Drug Administration [FDA]) and 1.3 (per European Medicines Agency [EMA]).
    Statistical Test of Hypothesis p-Value =0.2015
    Comments
    Method Log Rank
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.16
    Confidence Interval (2-Sided) 95%
    0.930 to 1.446
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first MACE for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 382 and 344 respectively; median time to first event (Q1, Q3) = 50.07 (23.00, 82.86) weeks versus 51.93 (27.79, 91.00) weeks, respectively. Statistical analysis from the pooled data has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.0725
    Comments
    Method Log Rank
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    1.012 to 1.355
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)
    Description The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates.
    Time Frame Baseline; Weeks 40 to 52

    Outcome Measure Data

    Analysis Population Description
    Randomized Population. Analyses of this population were based on the randomized treatment.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Measure Participants 862 863
    Least Squares Mean (Standard Error) [g/dL]
    0.43
    (0.044)
    0.44
    (0.044)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments Treatment comparison: Vadadustat minus Darbepoetin Alfa
    Type of Statistical Test Non-Inferiority
    Comments Establishment of non-inferiority was based on a margin of -0.75 g/dL applied to the difference in mean change: Vadadustat minus Darbepoetin alfa.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least squares mean difference
    Estimated Value -0.00
    Confidence Interval (2-Sided) 95%
    -0.10 to 0.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.05
    Estimation Comments
    4. Secondary Outcome
    Title Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis
    Description MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
    Time Frame Up to Week 208

    Outcome Measure Data

    Analysis Population Description
    Safety Population (PRO2TECT). Only those participants with MACE plus hospitalization for heart failure or thromboembolic event excluding vascular access thrombosis were analyzed for this outcome measure.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Measure Participants 197 195
    Median (Inter-Quartile Range) [Weeks]
    48.29
    49.29
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments Statistical analysis from study AKB-6548-CI-0015 has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.7770
    Comments
    Method Log Rank
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.851 to 1.268
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first MACE plus hospitalization for heart failure or thromboembolic events excluding vascular access thrombosis for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 451 and 424 respectively; median time to first event (Q1, Q3) = 42.86 (19.71, 73.43) weeks versus 43.86 (21.36, 80.43) weeks, respectively.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.2305
    Comments
    Method Log Rank
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.972 to 1.267
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Median Time to First Cardiovascular MACE
    Description MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
    Time Frame Up to Week 208

    Outcome Measure Data

    Analysis Population Description
    Safety Population (PRO2TECT). Only those participants with cardiovascular MACE events were analyzed for this outcome measure.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Measure Participants 89 83
    Median (Inter-Quartile Range) [Weeks]
    45.57
    50.29
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments Statistical analysis from study AKB-6548-CI-0015 has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.5509
    Comments
    Method Gray's Test
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.817 to 1.501
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first cardiovascular MACE for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 198 and 178 respectively; median time to first event (Q1, Q3) = 45.57 (21.71, 73.29) weeks versus 47.36 (20.00, 88.43) weeks, respectively. Statistical analysis from the pooled data has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.2531
    Comments
    Method Gray's Test
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.16
    Confidence Interval (2-Sided) 95%
    0.947 to 1.420
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Median Time to First Cardiovascular Death
    Description Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
    Time Frame Up to Week 208

    Outcome Measure Data

    Analysis Population Description
    Safety Population (PRO2TECT). Only those participants with cardiovascular death were analyzed for this outcome measure.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Measure Participants 56 66
    Median (Inter-Quartile Range) [Weeks]
    48.29
    54.21
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments Statistical analysis from study AKB-6548-CI-0015 has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.4184
    Comments
    Method Gray's test
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.88
    Confidence Interval (2-Sided) 95%
    0.610 to 1.258
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first cardiovascular death for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 127 and 131 respectively; median time to first event (Q1, Q3) = 48.29 (28.86, 76.14) weeks versus 48.43 (21.29, 92.29) weeks, respectively. Statistical analysis from the pooled data has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.8613
    Comments
    Method Gray's test
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.792 to 1.293
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Median Time to First All-cause Mortality
    Description Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
    Time Frame Up to Week 208

    Outcome Measure Data

    Analysis Population Description
    Safety Population (PRO2TECT). Only those participants with all-cause mortality were analyzed for this outcome measure.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    Measure Participants 139 139
    Median (Inter-Quartile Range) [Weeks]
    57.71
    62.14
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments Statistical analysis from study AKB-6548-CI-0015 has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.8041
    Comments
    Method Log Rank
    Comments Based on non-parametric analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.820 to 1.315
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vadadustat, Darbepoetin Alfa
    Comments MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first all-cause mortality for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 319 and 307 respectively; median time to first event (Q1, Q3) = 52.14 (28.71, 84.71) weeks versus 53.00 (30.71, 94.14) weeks, respectively. Statistical analysis from the pooled data has been reported in this section.
    Type of Statistical Test Non-Inferiority
    Comments The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA).
    Statistical Test of Hypothesis p-Value =0.4577
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.09
    Confidence Interval (2-Sided) 95%
    0.930 to 1.274
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Other Pre-specified Outcome
    Title Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)
    Description
    Time Frame Weeks 24 to 36

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Other Pre-specified Outcome
    Title Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)
    Description
    Time Frame Weeks 24 to 36

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Other Pre-specified Outcome
    Title Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)
    Description
    Time Frame Weeks 40 to 52

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    11. Other Pre-specified Outcome
    Title Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)
    Description
    Time Frame Weeks 40 to 52

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    12. Other Pre-specified Outcome
    Title Exploratory - Proportion of Participants With an Hb Increase of >1.0 g/dL From Baseline Visit
    Description
    Time Frame Baseline; up to Week 52

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    13. Other Pre-specified Outcome
    Title Exploratory - Time to Achieve Hb Increase of >1.0 g/dL From Baseline Visit
    Description
    Time Frame Baseline; up to Week 52

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    14. Other Pre-specified Outcome
    Title Exploratory - Mean Change in Hb Between Baseline (Mean Pretreatment Hb) and the Primary Evaluation Period (Mean Hb From Weeks 24 to 36) Stratified by Pre-baseline Erythropoiesis-stimulating Agent (ESA) Exposure
    Description
    Time Frame Baseline; Weeks 24 to 36

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    15. Other Pre-specified Outcome
    Title Exploratory - Mean Monthly Dose of Intravenous (IV) Elemental Iron Administered in Participants Who Have Received IV Iron
    Description
    Time Frame Up to Week 52

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    16. Other Pre-specified Outcome
    Title Exploratory - Proportion of Participants Receiving IV Iron Therapy
    Description
    Time Frame Up to Week 52

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    17. Other Pre-specified Outcome
    Title Exploratory - Proportion of Participants Receiving Red Blood Cells (RBCs) Transfusion(s)
    Description
    Time Frame Up to Week 52

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame Up to 208 weeks
    Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported in study AKB-6548-CI-0015 (NCT02680574). Of the participants randomized, 1723 participants were included in the Safety population (861 and 862 participants in the Vadadustat and Darbepoetin alfa treatment groups, respectively). Two randomized participants did not receive treatment.
    Arm/Group Title Vadadustat Darbepoetin Alfa
    Arm/Group Description Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
    All Cause Mortality
    Vadadustat Darbepoetin Alfa
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 139/861 (16.1%) 139/862 (16.1%)
    Serious Adverse Events
    Vadadustat Darbepoetin Alfa
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 504/861 (58.5%) 488/862 (56.6%)
    Blood and lymphatic system disorders
    Anaemia 16/861 (1.9%) 18/862 (2.1%)
    Blood loss anaemia 2/861 (0.2%) 4/862 (0.5%)
    Nephrogenic anaemia 1/861 (0.1%) 3/862 (0.3%)
    Thrombocytopenia 2/861 (0.2%) 1/862 (0.1%)
    Immune thrombocytopenia 0/861 (0%) 2/862 (0.2%)
    Iron deficiency anaemia 1/861 (0.1%) 1/862 (0.1%)
    Bone marrow failure 1/861 (0.1%) 0/862 (0%)
    Coagulopathy 0/861 (0%) 1/862 (0.1%)
    Pancytopenia 1/861 (0.1%) 0/862 (0%)
    Cardiac disorders
    Cardiac failure congestive 29/861 (3.4%) 31/862 (3.6%)
    Acute myocardial infarction 34/861 (3.9%) 24/862 (2.8%)
    Cardiac failure acute 15/861 (1.7%) 16/862 (1.9%)
    Atrial fibrillation 16/861 (1.9%) 13/862 (1.5%)
    Cardiac failure 10/861 (1.2%) 19/862 (2.2%)
    Cardiac arrest 9/861 (1%) 16/862 (1.9%)
    Coronary artery disease 7/861 (0.8%) 9/862 (1%)
    Cardiac failure chronic 7/861 (0.8%) 7/862 (0.8%)
    Acute left ventricular failure 5/861 (0.6%) 6/862 (0.7%)
    Myocardial infarction 7/861 (0.8%) 4/862 (0.5%)
    Left ventricular failure 3/861 (0.3%) 7/862 (0.8%)
    Angina unstable 3/861 (0.3%) 6/862 (0.7%)
    Atrial flutter 2/861 (0.2%) 5/862 (0.6%)
    Cardio-respiratory arrest 3/861 (0.3%) 4/862 (0.5%)
    Bradycardia 4/861 (0.5%) 2/862 (0.2%)
    Cardiogenic shock 2/861 (0.2%) 4/862 (0.5%)
    Cardiorenal syndrome 4/861 (0.5%) 2/862 (0.2%)
    Angina pectoris 1/861 (0.1%) 3/862 (0.3%)
    Cardiopulmonary failure 3/861 (0.3%) 1/862 (0.1%)
    Myocardial ischaemia 2/861 (0.2%) 2/862 (0.2%)
    Atrioventricular block 1/861 (0.1%) 2/862 (0.2%)
    Atrioventricular block complete 1/861 (0.1%) 2/862 (0.2%)
    Atrioventricular block second degree 1/861 (0.1%) 2/862 (0.2%)
    Coronary artery stenosis 1/861 (0.1%) 2/862 (0.2%)
    Pericardial effusion 2/861 (0.2%) 1/862 (0.1%)
    Pericarditis 1/861 (0.1%) 2/862 (0.2%)
    Ventricular fibrillation 1/861 (0.1%) 2/862 (0.2%)
    Acute coronary syndrome 2/861 (0.2%) 0/862 (0%)
    Arrhythmia 2/861 (0.2%) 0/862 (0%)
    Cardiomyopathy 1/861 (0.1%) 1/862 (0.1%)
    Sinus node dysfunction 0/861 (0%) 2/862 (0.2%)
    Ventricular tachycardia 0/861 (0%) 2/862 (0.2%)
    Bradyarrhythmia 0/861 (0%) 1/862 (0.1%)
    Cardiac tamponade 0/861 (0%) 1/862 (0.1%)
    Cardiac valve disease 0/861 (0%) 1/862 (0.1%)
    Heart valve incompetence 0/861 (0%) 1/862 (0.1%)
    Ischaemic cardiomyopathy 0/861 (0%) 1/862 (0.1%)
    Mitral valve calcification 0/861 (0%) 1/862 (0.1%)
    Mitral valve incompetence 0/861 (0%) 1/862 (0.1%)
    Pericarditis uraemic 0/861 (0%) 1/862 (0.1%)
    Pulseless electrical activity 0/861 (0%) 1/862 (0.1%)
    Right ventricular failure 0/861 (0%) 1/862 (0.1%)
    Tachycardia induced cardiomyopathy 1/861 (0.1%) 0/862 (0%)
    Tricuspid valve incompetence 0/861 (0%) 1/862 (0.1%)
    Ventricular hypokinesia 1/861 (0.1%) 0/862 (0%)
    Ear and labyrinth disorders
    Vertigo 1/861 (0.1%) 2/862 (0.2%)
    Vertigo positional 1/861 (0.1%) 1/862 (0.1%)
    Endocrine disorders
    Hypothyroidism 2/861 (0.2%) 1/862 (0.1%)
    Adrenal insufficiency 2/861 (0.2%) 0/862 (0%)
    Eye disorders
    Cataract diabetic 1/861 (0.1%) 0/862 (0%)
    Tractional retinal detachment 1/861 (0.1%) 0/862 (0%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 7/861 (0.8%) 6/862 (0.7%)
    Upper gastrointestinal haemorrhage 6/861 (0.7%) 3/862 (0.3%)
    Vomiting 3/861 (0.3%) 4/862 (0.5%)
    Diarrhoea 4/861 (0.5%) 2/862 (0.2%)
    Pancreatitis acute 3/861 (0.3%) 2/862 (0.2%)
    Colitis 3/861 (0.3%) 1/862 (0.1%)
    Gastritis 3/861 (0.3%) 1/862 (0.1%)
    Lower gastrointestinal haemorrhage 2/861 (0.2%) 2/862 (0.2%)
    Abdominal pain 2/861 (0.2%) 1/862 (0.1%)
    Chronic gastritis 1/861 (0.1%) 2/862 (0.2%)
    Duodenal ulcer haemorrhage 1/861 (0.1%) 2/862 (0.2%)
    Intestinal obstruction 2/861 (0.2%) 1/862 (0.1%)
    Rectal haemorrhage 3/861 (0.3%) 0/862 (0%)
    Small intestinal obstruction 1/861 (0.1%) 2/862 (0.2%)
    Abdominal pain upper 2/861 (0.2%) 0/862 (0%)
    Constipation 1/861 (0.1%) 1/862 (0.1%)
    Faecaloma 0/861 (0%) 2/862 (0.2%)
    Gastric haemorrhage 1/861 (0.1%) 1/862 (0.1%)
    Gastric ulcer 1/861 (0.1%) 1/862 (0.1%)
    Gastritis erosive 1/861 (0.1%) 1/862 (0.1%)
    Gastrointestinal vascular malformation haemorrhagic 1/861 (0.1%) 1/862 (0.1%)
    Haemorrhagic erosive gastritis 0/861 (0%) 2/862 (0.2%)
    Incarcerated inguinal hernia 1/861 (0.1%) 1/862 (0.1%)
    Large intestine perforation 1/861 (0.1%) 1/862 (0.1%)
    Peptic ulcer 2/861 (0.2%) 0/862 (0%)
    Pharyngo-oesophageal diverticulum 1/861 (0.1%) 1/862 (0.1%)
    Small intestinal haemorrhage 1/861 (0.1%) 1/862 (0.1%)
    Abdominal pain lower 1/861 (0.1%) 0/862 (0%)
    Colitis ischaemic 1/861 (0.1%) 0/862 (0%)
    Cyclic vomiting syndrome 0/861 (0%) 1/862 (0.1%)
    Diabetic gastroparesis 1/861 (0.1%) 0/862 (0%)
    Diverticulum intestinal haemorrhagic 0/861 (0%) 1/862 (0.1%)
    Duodenal ulcer 1/861 (0.1%) 0/862 (0%)
    Duodenitis 1/861 (0.1%) 0/862 (0%)
    Dyschezia 1/861 (0.1%) 0/862 (0%)
    Femoral hernia incarcerated 0/861 (0%) 1/862 (0.1%)
    Gastric antral vascular ectasia 1/861 (0.1%) 0/862 (0%)
    Gastric perforation 1/861 (0.1%) 0/862 (0%)
    Gastric ulcer haemorrhage 0/861 (0%) 1/862 (0.1%)
    Gastrointestinal angiectasia 0/861 (0%) 1/862 (0.1%)
    Gastrointestinal inflammation 1/861 (0.1%) 0/862 (0%)
    Gastrointestinal polyp haemorrhage 0/861 (0%) 1/862 (0.1%)
    Gastrooesophageal reflux disease 1/861 (0.1%) 0/862 (0%)
    Gingival bleeding 1/861 (0.1%) 0/862 (0%)
    Haematemesis 1/861 (0.1%) 0/862 (0%)
    Haematochezia 1/861 (0.1%) 0/862 (0%)
    Haemorrhoidal haemorrhage 1/861 (0.1%) 0/862 (0%)
    Intestinal perforation 0/861 (0%) 1/862 (0.1%)
    Large intestinal haemorrhage 1/861 (0.1%) 0/862 (0%)
    Large intestine polyp 0/861 (0%) 1/862 (0.1%)
    Nausea 0/861 (0%) 1/862 (0.1%)
    Obstructive pancreatitis 0/861 (0%) 1/862 (0.1%)
    Oedematous pancreatitis 1/861 (0.1%) 0/862 (0%)
    Oesophageal ulcer haemorrhage 0/861 (0%) 1/862 (0.1%)
    Oesophageal varices haemorrhage 1/861 (0.1%) 0/862 (0%)
    Pancreatic mass 0/861 (0%) 1/862 (0.1%)
    Pancreatitis 0/861 (0%) 1/862 (0.1%)
    Pneumatosis intestinalis 0/861 (0%) 1/862 (0.1%)
    Portal hypertensive gastropathy 1/861 (0.1%) 0/862 (0%)
    Proctitis 0/861 (0%) 1/862 (0.1%)
    Small intestinal perforation 1/861 (0.1%) 0/862 (0%)
    Umbilical hernia 0/861 (0%) 1/862 (0.1%)
    Varices oesophageal 0/861 (0%) 1/862 (0.1%)
    General disorders
    Death 20/861 (2.3%) 13/862 (1.5%)
    Multiple organ dysfunction syndrome 4/861 (0.5%) 3/862 (0.3%)
    Non-cardiac chest pain 5/861 (0.6%) 2/862 (0.2%)
    Asthenia 1/861 (0.1%) 5/862 (0.6%)
    Chest pain 1/861 (0.1%) 3/862 (0.3%)
    Generalised oedema 2/861 (0.2%) 2/862 (0.2%)
    Catheter site haemorrhage 1/861 (0.1%) 2/862 (0.2%)
    Complication associated with device 3/861 (0.3%) 0/862 (0%)
    Oedema peripheral 1/861 (0.1%) 2/862 (0.2%)
    Pyrexia 3/861 (0.3%) 0/862 (0%)
    General physical health deterioration 2/861 (0.2%) 0/862 (0%)
    Sudden death 1/861 (0.1%) 1/862 (0.1%)
    Chest discomfort 1/861 (0.1%) 0/862 (0%)
    Fatigue 1/861 (0.1%) 0/862 (0%)
    Hypothermia 0/861 (0%) 1/862 (0.1%)
    Impaired healing 0/861 (0%) 1/862 (0.1%)
    Malaise 1/861 (0.1%) 0/862 (0%)
    Sudden cardiac death 1/861 (0.1%) 0/862 (0%)
    Systemic inflammatory response syndrome 1/861 (0.1%) 0/862 (0%)
    Treatment noncompliance 0/861 (0%) 1/862 (0.1%)
    Hepatobiliary disorders
    Cholecystitis acute 3/861 (0.3%) 3/862 (0.3%)
    Cholelithiasis 2/861 (0.2%) 1/862 (0.1%)
    Drug-induced liver injury 2/861 (0.2%) 1/862 (0.1%)
    Acute hepatic failure 1/861 (0.1%) 1/862 (0.1%)
    Cholecystitis 2/861 (0.2%) 0/862 (0%)
    Cholecystitis chronic 0/861 (0%) 2/862 (0.2%)
    Liver injury 1/861 (0.1%) 1/862 (0.1%)
    Chronic hepatic failure 1/861 (0.1%) 0/862 (0%)
    Gallbladder rupture 0/861 (0%) 1/862 (0.1%)
    Granulomatous liver disease 0/861 (0%) 1/862 (0.1%)
    Hepatitis alcoholic 1/861 (0.1%) 0/862 (0%)
    Hepatocellular injury 1/861 (0.1%) 0/862 (0%)
    Ischaemic hepatitis 1/861 (0.1%) 0/862 (0%)
    Non-alcoholic steatohepatitis 0/861 (0%) 1/862 (0.1%)
    Steatohepatitis 1/861 (0.1%) 0/862 (0%)
    Immune system disorders
    Drug hypersensitivity 1/861 (0.1%) 2/862 (0.2%)
    Kidney transplant rejection 0/861 (0%) 2/862 (0.2%)
    Transplant rejection 2/861 (0.2%) 0/862 (0%)
    Infections and infestations
    Pneumonia 56/861 (6.5%) 49/862 (5.7%)
    Urinary tract infection 20/861 (2.3%) 20/862 (2.3%)
    Sepsis 17/861 (2%) 16/862 (1.9%)
    Cellulitis 6/861 (0.7%) 17/862 (2%)
    Septic shock 10/861 (1.2%) 7/862 (0.8%)
    Osteomyelitis 5/861 (0.6%) 6/862 (0.7%)
    Clostridium difficile colitis 8/861 (0.9%) 2/862 (0.2%)
    Urosepsis 6/861 (0.7%) 4/862 (0.5%)
    Pyelonephritis acute 3/861 (0.3%) 5/862 (0.6%)
    Gangrene 3/861 (0.3%) 4/862 (0.5%)
    Gastroenteritis 3/861 (0.3%) 4/862 (0.5%)
    Peritonitis 4/861 (0.5%) 3/862 (0.3%)
    Pyelonephritis chronic 4/861 (0.5%) 3/862 (0.3%)
    Influenza 3/861 (0.3%) 3/862 (0.3%)
    Pyelonephritis 4/861 (0.5%) 2/862 (0.2%)
    Device related infection 2/861 (0.2%) 3/862 (0.3%)
    Diverticulitis 3/861 (0.3%) 2/862 (0.2%)
    Staphylococcal sepsis 1/861 (0.1%) 4/862 (0.5%)
    Bronchitis 3/861 (0.3%) 1/862 (0.1%)
    Cystitis 2/861 (0.2%) 2/862 (0.2%)
    Device related sepsis 2/861 (0.2%) 2/862 (0.2%)
    Peritonitis bacterial 2/861 (0.2%) 2/862 (0.2%)
    Pneumonia bacterial 2/861 (0.2%) 2/862 (0.2%)
    Staphylococcal bacteraemia 0/861 (0%) 4/862 (0.5%)
    Upper respiratory tract infection 3/861 (0.3%) 1/862 (0.1%)
    Urinary tract infection bacterial 3/861 (0.3%) 1/862 (0.1%)
    Abscess limb 2/861 (0.2%) 1/862 (0.1%)
    Anal abscess 2/861 (0.2%) 1/862 (0.1%)
    Appendicitis 0/861 (0%) 3/862 (0.3%)
    Arteriovenous fistula site infection 1/861 (0.1%) 2/862 (0.2%)
    Diabetic foot infection 2/861 (0.2%) 1/862 (0.1%)
    Escherichia urinary tract infection 1/861 (0.1%) 2/862 (0.2%)
    Infective exacerbation of bronchiectasis 0/861 (0%) 3/862 (0.3%)
    Viral infection 1/861 (0.1%) 2/862 (0.2%)
    Bacteraemia 0/861 (0%) 2/862 (0.2%)
    Clostridium difficile infection 2/861 (0.2%) 0/862 (0%)
    Endocarditis 1/861 (0.1%) 1/862 (0.1%)
    Escherichia bacteraemia 0/861 (0%) 2/862 (0.2%)
    Escherichia sepsis 0/861 (0%) 2/862 (0.2%)
    Intervertebral discitis 2/861 (0.2%) 0/862 (0%)
    Lower respiratory tract infection 0/861 (0%) 2/862 (0.2%)
    Pneumococcal sepsis 1/861 (0.1%) 1/862 (0.1%)
    Pneumonia staphylococcal 2/861 (0.2%) 0/862 (0%)
    Pulmonary sepsis 1/861 (0.1%) 1/862 (0.1%)
    Sinusitis 1/861 (0.1%) 1/862 (0.1%)
    Staphylococcal infection 1/861 (0.1%) 1/862 (0.1%)
    Abdominal wall abscess 0/861 (0%) 1/862 (0.1%)
    Abscess neck 0/861 (0%) 1/862 (0.1%)
    Acute hepatitis C 1/861 (0.1%) 0/862 (0%)
    Appendicitis perforated 1/861 (0.1%) 0/862 (0%)
    Atypical pneumonia 1/861 (0.1%) 0/862 (0%)
    Bacterial sepsis 1/861 (0.1%) 0/862 (0%)
    Biliary sepsis 1/861 (0.1%) 0/862 (0%)
    Bronchitis viral 0/861 (0%) 1/862 (0.1%)
    COVID-19 1/861 (0.1%) 0/862 (0%)
    Campylobacter gastroenteritis 1/861 (0.1%) 0/862 (0%)
    Candida infection 0/861 (0%) 1/862 (0.1%)
    Cardiac valve vegetation 0/861 (0%) 1/862 (0.1%)
    Catheter bacteraemia 0/861 (0%) 1/862 (0.1%)
    Catheter site cellulitis 1/861 (0.1%) 0/862 (0%)
    Cryptosporidiosis infection 1/861 (0.1%) 0/862 (0%)
    Cystitis bacterial 0/861 (0%) 1/862 (0.1%)
    Cystitis klebsiella 1/861 (0.1%) 0/862 (0%)
    Cytomegalovirus infection 1/861 (0.1%) 0/862 (0%)
    Endocarditis bacterial 0/861 (0%) 1/862 (0.1%)
    Endocarditis staphylococcal 0/861 (0%) 1/862 (0.1%)
    Enterobacter infection 0/861 (0%) 1/862 (0.1%)
    Enterocolitis bacterial 1/861 (0.1%) 0/862 (0%)
    Escherichia infection 0/861 (0%) 1/862 (0.1%)
    Escherichia pyelonephritis 0/861 (0%) 1/862 (0.1%)
    Fournier's gangrene 0/861 (0%) 1/862 (0.1%)
    Fungal peritonitis 0/861 (0%) 1/862 (0.1%)
    Furuncle 0/861 (0%) 1/862 (0.1%)
    Gastritis viral 1/861 (0.1%) 0/862 (0%)
    Gastroenteritis clostridial 1/861 (0.1%) 0/862 (0%)
    Gastroenteritis viral 1/861 (0.1%) 0/862 (0%)
    Gastrointestinal infection 0/861 (0%) 1/862 (0.1%)
    Haematoma infection 1/861 (0.1%) 0/862 (0%)
    Helicobacter gastritis 1/861 (0.1%) 0/862 (0%)
    Infected skin ulcer 1/861 (0.1%) 0/862 (0%)
    Infection 1/861 (0.1%) 0/862 (0%)
    Intestinal sepsis 1/861 (0.1%) 0/862 (0%)
    Klebsiella infection 1/861 (0.1%) 0/862 (0%)
    Localised infection 1/861 (0.1%) 0/862 (0%)
    Mastoiditis 1/861 (0.1%) 0/862 (0%)
    Osteomyelitis bacterial 1/861 (0.1%) 0/862 (0%)
    Parainfluenzae virus infection 1/861 (0.1%) 0/862 (0%)
    Parotid abscess 0/861 (0%) 1/862 (0.1%)
    Perirectal abscess 1/861 (0.1%) 0/862 (0%)
    Pharyngeal abscess 0/861 (0%) 1/862 (0.1%)
    Pneumonia escherichia 0/861 (0%) 1/862 (0.1%)
    Pneumonia influenzal 0/861 (0%) 1/862 (0.1%)
    Pneumonia klebsiella 0/861 (0%) 1/862 (0.1%)
    Pneumonia legionella 1/861 (0.1%) 0/862 (0%)
    Pneumonia respiratory syncytial viral 1/861 (0.1%) 0/862 (0%)
    Pneumonia viral 0/861 (0%) 1/862 (0.1%)
    Post procedural cellulitis 1/861 (0.1%) 0/862 (0%)
    Post procedural infection 1/861 (0.1%) 0/862 (0%)
    Proteus infection 0/861 (0%) 1/862 (0.1%)
    Pseudomonal bacteraemia 1/861 (0.1%) 0/862 (0%)
    Pulmonary tuberculosis 1/861 (0.1%) 0/862 (0%)
    Pyonephrosis 1/861 (0.1%) 0/862 (0%)
    Renal graft infection 1/861 (0.1%) 0/862 (0%)
    Respiratory tract infection 0/861 (0%) 1/862 (0.1%)
    Salmonella bacteraemia 1/861 (0.1%) 0/862 (0%)
    Scarlet fever 1/861 (0.1%) 0/862 (0%)
    Scrotal abscess 1/861 (0.1%) 0/862 (0%)
    Serratia bacteraemia 0/861 (0%) 1/862 (0.1%)
    Shunt infection 0/861 (0%) 1/862 (0.1%)
    Tinea pedis 0/861 (0%) 1/862 (0.1%)
    Tooth abscess 1/861 (0.1%) 0/862 (0%)
    Tracheitis 0/861 (0%) 1/862 (0.1%)
    Tracheobronchitis 1/861 (0.1%) 0/862 (0%)
    Urinary tract infection pseudomonal 1/861 (0.1%) 0/862 (0%)
    Vestibular neuronitis 1/861 (0.1%) 0/862 (0%)
    Viral diarrhoea 1/861 (0.1%) 0/862 (0%)
    Viral upper respiratory tract infection 1/861 (0.1%) 0/862 (0%)
    Wound infection 0/861 (0%) 1/862 (0.1%)
    Wound infection pseudomonas 0/861 (0%) 1/862 (0.1%)
    Injury, poisoning and procedural complications
    Fall 8/861 (0.9%) 12/862 (1.4%)
    Hip fracture 12/861 (1.4%) 2/862 (0.2%)
    Arteriovenous fistula thrombosis 1/861 (0.1%) 7/862 (0.8%)
    Femoral neck fracture 4/861 (0.5%) 3/862 (0.3%)
    Arteriovenous fistula site complication 2/861 (0.2%) 3/862 (0.3%)
    Wrist fracture 2/861 (0.2%) 2/862 (0.2%)
    Femur fracture 1/861 (0.1%) 2/862 (0.2%)
    Humerus fracture 1/861 (0.1%) 2/862 (0.2%)
    Lower limb fracture 2/861 (0.2%) 1/862 (0.1%)
    Rib fracture 0/861 (0%) 3/862 (0.3%)
    Spinal compression fracture 1/861 (0.1%) 2/862 (0.2%)
    Subdural haematoma 0/861 (0%) 3/862 (0.3%)
    Tibia fracture 2/861 (0.2%) 1/862 (0.1%)
    Toxicity to various agents 2/861 (0.2%) 1/862 (0.1%)
    Wound dehiscence 1/861 (0.1%) 2/862 (0.2%)
    Accidental overdose 2/861 (0.2%) 0/862 (0%)
    Ankle fracture 2/861 (0.2%) 0/862 (0%)
    Arteriovenous fistula maturation failure 2/861 (0.2%) 0/862 (0%)
    Arteriovenous fistula site haematoma 0/861 (0%) 2/862 (0.2%)
    Head injury 1/861 (0.1%) 1/862 (0.1%)
    Joint dislocation 0/861 (0%) 2/862 (0.2%)
    Multiple injuries 2/861 (0.2%) 0/862 (0%)
    Road traffic accident 1/861 (0.1%) 1/862 (0.1%)
    Traumatic intracranial haemorrhage 1/861 (0.1%) 1/862 (0.1%)
    Upper limb fracture 2/861 (0.2%) 0/862 (0%)
    Animal bite 0/861 (0%) 1/862 (0.1%)
    Arteriovenous fistula aneurysm 0/861 (0%) 1/862 (0.1%)
    Arteriovenous fistula site haemorrhage 0/861 (0%) 1/862 (0.1%)
    Brain contusion 1/861 (0.1%) 0/862 (0%)
    Chest injury 0/861 (0%) 1/862 (0.1%)
    Comminuted fracture 1/861 (0.1%) 0/862 (0%)
    Complications of transplanted kidney 1/861 (0.1%) 0/862 (0%)
    Concussion 0/861 (0%) 1/862 (0.1%)
    Contusion 0/861 (0%) 1/862 (0.1%)
    Craniocerebral injury 1/861 (0.1%) 0/862 (0%)
    Device placement issue 1/861 (0.1%) 0/862 (0%)
    Eye contusion 1/861 (0.1%) 0/862 (0%)
    Facial bones fracture 1/861 (0.1%) 0/862 (0%)
    Fibula fracture 1/861 (0.1%) 0/862 (0%)
    Foot fracture 0/861 (0%) 1/862 (0.1%)
    Forearm fracture 1/861 (0.1%) 0/862 (0%)
    Fractured sacrum 0/861 (0%) 1/862 (0.1%)
    Multiple fractures 1/861 (0.1%) 0/862 (0%)
    Muscle strain 0/861 (0%) 1/862 (0.1%)
    Pelvic fracture 0/861 (0%) 1/862 (0.1%)
    Periorbital haematoma 0/861 (0%) 1/862 (0.1%)
    Peritoneal dialysis complication 1/861 (0.1%) 0/862 (0%)
    Post procedural haematuria 1/861 (0.1%) 0/862 (0%)
    Radiation pneumonitis 0/861 (0%) 1/862 (0.1%)
    Radius fracture 0/861 (0%) 1/862 (0.1%)
    Shunt malfunction 0/861 (0%) 1/862 (0.1%)
    Shunt occlusion 1/861 (0.1%) 0/862 (0%)
    Shunt thrombosis 0/861 (0%) 1/862 (0.1%)
    Skin laceration 0/861 (0%) 1/862 (0.1%)
    Spinal fracture 0/861 (0%) 1/862 (0.1%)
    Tendon injury 1/861 (0.1%) 0/862 (0%)
    Thoracic vertebral fracture 0/861 (0%) 1/862 (0.1%)
    Traumatic haematoma 0/861 (0%) 1/862 (0.1%)
    Ulna fracture 0/861 (0%) 1/862 (0.1%)
    Vascular access site haematoma 0/861 (0%) 1/862 (0.1%)
    Vascular access site thrombosis 1/861 (0.1%) 0/862 (0%)
    Wound evisceration 0/861 (0%) 1/862 (0.1%)
    Investigations
    Alanine aminotransferase increased 7/861 (0.8%) 8/862 (0.9%)
    Aspartate aminotransferase increased 4/861 (0.5%) 6/862 (0.7%)
    Hepatic enzyme increased 1/861 (0.1%) 3/862 (0.3%)
    Transaminases increased 1/861 (0.1%) 3/862 (0.3%)
    Blood potassium increased 0/861 (0%) 2/862 (0.2%)
    International normalised ratio increased 2/861 (0.2%) 0/862 (0%)
    Anticoagulation drug level below therapeutic 0/861 (0%) 1/862 (0.1%)
    Blood bilirubin increased 1/861 (0.1%) 0/862 (0%)
    Blood glucose fluctuation 1/861 (0.1%) 0/862 (0%)
    Blood pressure increased 0/861 (0%) 1/862 (0.1%)
    Electrocardiogram repolarisation abnormality 0/861 (0%) 1/862 (0.1%)
    Glomerular filtration rate decreased 1/861 (0.1%) 0/862 (0%)
    Prothrombin time prolonged 0/861 (0%) 1/862 (0.1%)
    Weight decreased 1/861 (0.1%) 0/862 (0%)
    Metabolism and nutrition disorders
    Fluid overload 17/861 (2%) 12/862 (1.4%)
    Dehydration 16/861 (1.9%) 10/862 (1.2%)
    Hyperkalaemia 13/861 (1.5%) 9/862 (1%)
    Hypoglycaemia 13/861 (1.5%) 6/862 (0.7%)
    Diabetic ketoacidosis 4/861 (0.5%) 5/862 (0.6%)
    Diabetes mellitus 3/861 (0.3%) 5/862 (0.6%)
    Hyponatraemia 2/861 (0.2%) 6/862 (0.7%)
    Hypovolaemia 3/861 (0.3%) 5/862 (0.6%)
    Hyperglycaemia 3/861 (0.3%) 4/862 (0.5%)
    Hypervolaemia 4/861 (0.5%) 3/862 (0.3%)
    Diabetic metabolic decompensation 3/861 (0.3%) 2/862 (0.2%)
    Metabolic acidosis 3/861 (0.3%) 1/862 (0.1%)
    Diabetes mellitus inadequate control 1/861 (0.1%) 2/862 (0.2%)
    Gout 2/861 (0.2%) 1/862 (0.1%)
    Hypokalaemia 2/861 (0.2%) 1/862 (0.1%)
    Malnutrition 1/861 (0.1%) 1/862 (0.1%)
    Obesity 2/861 (0.2%) 0/862 (0%)
    Acidosis 0/861 (0%) 1/862 (0.1%)
    Cachexia 0/861 (0%) 1/862 (0.1%)
    Decreased appetite 1/861 (0.1%) 0/862 (0%)
    Electrolyte imbalance 1/861 (0.1%) 0/862 (0%)
    Failure to thrive 0/861 (0%) 1/862 (0.1%)
    Hypercalcaemia 0/861 (0%) 1/862 (0.1%)
    Hyperglycaemic hyperosmolar nonketotic syndrome 1/861 (0.1%) 0/862 (0%)
    Hypomagnesaemia 0/861 (0%) 1/862 (0.1%)
    Type 2 diabetes mellitus 0/861 (0%) 1/862 (0.1%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 5/861 (0.6%) 6/862 (0.7%)
    Arthralgia 3/861 (0.3%) 0/862 (0%)
    Rhabdomyolysis 3/861 (0.3%) 0/862 (0%)
    Spinal osteoarthritis 1/861 (0.1%) 2/862 (0.2%)
    Spinal stenosis 1/861 (0.1%) 2/862 (0.2%)
    Arthritis 1/861 (0.1%) 1/862 (0.1%)
    Back pain 1/861 (0.1%) 1/862 (0.1%)
    Flank pain 0/861 (0%) 2/862 (0.2%)
    Polymyalgia rheumatica 2/861 (0.2%) 0/862 (0%)
    Spondylolisthesis 1/861 (0.1%) 1/862 (0.1%)
    Ankylosing spondylitis 0/861 (0%) 1/862 (0.1%)
    Bursitis 1/861 (0.1%) 0/862 (0%)
    Cervical spinal stenosis 1/861 (0.1%) 0/862 (0%)
    Chest wall haematoma 0/861 (0%) 1/862 (0.1%)
    Costochondritis 1/861 (0.1%) 0/862 (0%)
    Diabetic amyotrophy 0/861 (0%) 1/862 (0.1%)
    Groin pain 1/861 (0.1%) 0/862 (0%)
    Intervertebral disc degeneration 0/861 (0%) 1/862 (0.1%)
    Lumbar spinal stenosis 0/861 (0%) 1/862 (0.1%)
    Muscle spasms 0/861 (0%) 1/862 (0.1%)
    Musculoskeletal chest pain 0/861 (0%) 1/862 (0.1%)
    Musculoskeletal pain 1/861 (0.1%) 0/862 (0%)
    Myopathy endocrine 0/861 (0%) 1/862 (0.1%)
    Osteonecrosis 0/861 (0%) 1/862 (0.1%)
    Polyarthritis 1/861 (0.1%) 0/862 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Plasma cell myeloma 3/861 (0.3%) 3/862 (0.3%)
    Basal cell carcinoma 4/861 (0.5%) 0/862 (0%)
    Invasive ductal breast carcinoma 3/861 (0.3%) 1/862 (0.1%)
    Prostate cancer 1/861 (0.1%) 3/862 (0.3%)
    Myelodysplastic syndrome 2/861 (0.2%) 1/862 (0.1%)
    Prostate cancer recurrent 1/861 (0.1%) 2/862 (0.2%)
    Adenocarcinoma of colon 1/861 (0.1%) 1/862 (0.1%)
    Breast cancer 0/861 (0%) 2/862 (0.2%)
    Hepatic cancer 1/861 (0.1%) 1/862 (0.1%)
    Lung neoplasm malignant 0/861 (0%) 2/862 (0.2%)
    Squamous cell carcinoma of skin 2/861 (0.2%) 0/862 (0%)
    Acute myeloid leukaemia 0/861 (0%) 1/862 (0.1%)
    Adenocarcinoma 0/861 (0%) 1/862 (0.1%)
    Adenocarcinoma gastric 0/861 (0%) 1/862 (0.1%)
    Adenocarcinoma pancreas 0/861 (0%) 1/862 (0.1%)
    Bladder cancer 1/861 (0.1%) 0/862 (0%)
    Bladder cancer recurrent 0/861 (0%) 1/862 (0.1%)
    Brain neoplasm 0/861 (0%) 1/862 (0.1%)
    Breast cancer metastatic 0/861 (0%) 1/862 (0.1%)
    Cancer pain 1/861 (0.1%) 0/862 (0%)
    Cerebellar tumour 0/861 (0%) 1/862 (0.1%)
    Cervix carcinoma 1/861 (0.1%) 0/862 (0%)
    Cholangiocarcinoma 0/861 (0%) 1/862 (0.1%)
    Clear cell renal cell carcinoma 1/861 (0.1%) 0/862 (0%)
    Colon cancer 1/861 (0.1%) 0/862 (0%)
    Gallbladder cancer 1/861 (0.1%) 0/862 (0%)
    Gastric cancer 1/861 (0.1%) 0/862 (0%)
    Gastric cancer stage IV 0/861 (0%) 1/862 (0.1%)
    Hairy cell leukaemia 0/861 (0%) 1/862 (0.1%)
    Hepatocellular carcinoma 0/861 (0%) 1/862 (0.1%)
    Lung cancer metastatic 0/861 (0%) 1/862 (0.1%)
    Lung neoplasm 0/861 (0%) 1/862 (0.1%)
    Metastases to central nervous system 0/861 (0%) 1/862 (0.1%)
    Metastatic bronchial carcinoma 1/861 (0.1%) 0/862 (0%)
    Neoplasm malignant 1/861 (0.1%) 0/862 (0%)
    Non-small cell lung cancer 0/861 (0%) 1/862 (0.1%)
    Non-small cell lung cancer stage I 1/861 (0.1%) 0/862 (0%)
    Oesophageal carcinoma 0/861 (0%) 1/862 (0.1%)
    Oesophageal squamous cell carcinoma 1/861 (0.1%) 0/862 (0%)
    Ovarian adenoma 1/861 (0.1%) 0/862 (0%)
    Pancreatic carcinoma metastatic 1/861 (0.1%) 0/862 (0%)
    Papillary thyroid cancer 1/861 (0.1%) 0/862 (0%)
    Renal cancer stage II 1/861 (0.1%) 0/862 (0%)
    Renal neoplasm 0/861 (0%) 1/862 (0.1%)
    Seborrhoeic keratosis 1/861 (0.1%) 0/862 (0%)
    Squamous cell carcinoma of pharynx 1/861 (0.1%) 0/862 (0%)
    Transitional cell carcinoma 0/861 (0%) 1/862 (0.1%)
    Nervous system disorders
    Syncope 6/861 (0.7%) 9/862 (1%)
    Metabolic encephalopathy 5/861 (0.6%) 9/862 (1%)
    Cerebrovascular accident 7/861 (0.8%) 4/862 (0.5%)
    Ischaemic stroke 8/861 (0.9%) 2/862 (0.2%)
    Transient ischaemic attack 6/861 (0.7%) 3/862 (0.3%)
    Encephalopathy 3/861 (0.3%) 5/862 (0.6%)
    Haemorrhagic stroke 3/861 (0.3%) 1/862 (0.1%)
    Seizure 2/861 (0.2%) 2/862 (0.2%)
    Cerebral infarction 0/861 (0%) 2/862 (0.2%)
    Dementia 1/861 (0.1%) 1/862 (0.1%)
    Dizziness 2/861 (0.2%) 0/862 (0%)
    Ischaemic cerebral infarction 1/861 (0.1%) 1/862 (0.1%)
    Migraine 1/861 (0.1%) 1/862 (0.1%)
    Subarachnoid haemorrhage 2/861 (0.2%) 0/862 (0%)
    Toxic encephalopathy 1/861 (0.1%) 1/862 (0.1%)
    Uraemic encephalopathy 2/861 (0.2%) 0/862 (0%)
    Brain stem stroke 0/861 (0%) 1/862 (0.1%)
    Cerebellar infarction 0/861 (0%) 1/862 (0.1%)
    Cerebral artery thrombosis 0/861 (0%) 1/862 (0.1%)
    Cerebral haemorrhage 1/861 (0.1%) 0/862 (0%)
    Cerebral ischaemia 0/861 (0%) 1/862 (0.1%)
    Dementia Alzheimer's type 1/861 (0.1%) 0/862 (0%)
    Diabetic coma 1/861 (0.1%) 0/862 (0%)
    Diabetic encephalopathy 1/861 (0.1%) 0/862 (0%)
    Embolic cerebral infarction 1/861 (0.1%) 0/862 (0%)
    Haemorrhage intracranial 1/861 (0.1%) 0/862 (0%)
    Headache 1/861 (0.1%) 0/862 (0%)
    Hepatic encephalopathy 0/861 (0%) 1/862 (0.1%)
    Hypoglycaemic encephalopathy 0/861 (0%) 1/862 (0.1%)
    Hypoglycaemic unconsciousness 0/861 (0%) 1/862 (0.1%)
    Hypoxic-ischaemic encephalopathy 1/861 (0.1%) 0/862 (0%)
    Intraventricular haemorrhage 0/861 (0%) 1/862 (0.1%)
    Lacunar stroke 0/861 (0%) 1/862 (0.1%)
    Mental impairment 0/861 (0%) 1/862 (0.1%)
    Posterior reversible encephalopathy syndrome 0/861 (0%) 1/862 (0.1%)
    Presyncope 1/861 (0.1%) 0/862 (0%)
    Sciatica 0/861 (0%) 1/862 (0.1%)
    Status epilepticus 1/861 (0.1%) 0/862 (0%)
    Thalamic infarction 1/861 (0.1%) 0/862 (0%)
    Thrombotic stroke 0/861 (0%) 1/862 (0.1%)
    VIth nerve disorder 0/861 (0%) 1/862 (0.1%)
    Vertigo CNS origin 0/861 (0%) 1/862 (0.1%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 1/861 (0.1%) 0/862 (0%)
    Product Issues
    Device dislocation 0/861 (0%) 3/862 (0.3%)
    Device occlusion 0/861 (0%) 2/862 (0.2%)
    Psychiatric disorders
    Mental status changes 2/861 (0.2%) 5/862 (0.6%)
    Depression 1/861 (0.1%) 3/862 (0.3%)
    Delirium 2/861 (0.2%) 1/862 (0.1%)
    Anger 0/861 (0%) 1/862 (0.1%)
    Anxiety 0/861 (0%) 1/862 (0.1%)
    Major depression 1/861 (0.1%) 0/862 (0%)
    Panic attack 1/861 (0.1%) 0/862 (0%)
    Psychotic disorder 0/861 (0%) 1/862 (0.1%)
    Schizophrenia 0/861 (0%) 1/862 (0.1%)
    Suicidal ideation 0/861 (0%) 1/862 (0.1%)
    Renal and urinary disorders
    End stage renal disease 232/861 (26.9%) 238/862 (27.6%)
    Acute kidney injury 34/861 (3.9%) 32/862 (3.7%)
    Diabetic nephropathy 6/861 (0.7%) 6/862 (0.7%)
    Azotaemia 4/861 (0.5%) 6/862 (0.7%)
    Renal impairment 3/861 (0.3%) 4/862 (0.5%)
    Urinary tract obstruction 3/861 (0.3%) 2/862 (0.2%)
    Renal tubular necrosis 3/861 (0.3%) 1/862 (0.1%)
    Chronic kidney disease 0/861 (0%) 3/862 (0.3%)
    Glomerulonephritis 2/861 (0.2%) 1/862 (0.1%)
    Hydronephrosis 2/861 (0.2%) 1/862 (0.1%)
    Urethral stenosis 0/861 (0%) 3/862 (0.3%)
    Cystitis haemorrhagic 2/861 (0.2%) 0/862 (0%)
    Dysuria 1/861 (0.1%) 1/862 (0.1%)
    Haematuria 1/861 (0.1%) 1/862 (0.1%)
    Renal failure 0/861 (0%) 2/862 (0.2%)
    Urinary retention 1/861 (0.1%) 1/862 (0.1%)
    Acute phosphate nephropathy 0/861 (0%) 1/862 (0.1%)
    Calculus urinary 0/861 (0%) 1/862 (0.1%)
    Glomerulonephritis membranoproliferative 1/861 (0.1%) 0/862 (0%)
    Glomerulosclerosis 1/861 (0.1%) 0/862 (0%)
    Hypertensive nephropathy 0/861 (0%) 1/862 (0.1%)
    Nephrolithiasis 1/861 (0.1%) 0/862 (0%)
    Nephropathy toxic 1/861 (0.1%) 0/862 (0%)
    Nephrotic syndrome 0/861 (0%) 1/862 (0.1%)
    Neurogenic bladder 1/861 (0.1%) 0/862 (0%)
    Reflux nephropathy 0/861 (0%) 1/862 (0.1%)
    Renal mass 1/861 (0.1%) 0/862 (0%)
    Renal papillary necrosis 1/861 (0.1%) 0/862 (0%)
    Renal vascular thrombosis 0/861 (0%) 1/862 (0.1%)
    Ureteric obstruction 1/861 (0.1%) 0/862 (0%)
    Ureteric stenosis 0/861 (0%) 1/862 (0.1%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/861 (0%) 3/862 (0.3%)
    Uterine prolapse 1/861 (0.1%) 1/862 (0.1%)
    Cervical polyp 1/861 (0.1%) 0/862 (0%)
    Endometriosis 1/861 (0.1%) 0/862 (0%)
    Female genital tract fistula 0/861 (0%) 1/862 (0.1%)
    Prostatitis 1/861 (0.1%) 0/862 (0%)
    Uterine polyp 0/861 (0%) 1/862 (0.1%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 14/861 (1.6%) 9/862 (1%)
    Chronic obstructive pulmonary disease 10/861 (1.2%) 7/862 (0.8%)
    Pulmonary oedema 5/861 (0.6%) 11/862 (1.3%)
    Pneumonia aspiration 5/861 (0.6%) 7/862 (0.8%)
    Respiratory failure 4/861 (0.5%) 7/862 (0.8%)
    Acute pulmonary oedema 2/861 (0.2%) 6/862 (0.7%)
    Pleural effusion 1/861 (0.1%) 7/862 (0.8%)
    Pulmonary hypertension 4/861 (0.5%) 3/862 (0.3%)
    Dyspnoea 2/861 (0.2%) 4/862 (0.5%)
    Pulmonary embolism 3/861 (0.3%) 3/862 (0.3%)
    Asthma 2/861 (0.2%) 1/862 (0.1%)
    Interstitial lung disease 2/861 (0.2%) 1/862 (0.1%)
    Bronchitis chronic 1/861 (0.1%) 1/862 (0.1%)
    Emphysema 2/861 (0.2%) 0/862 (0%)
    Epistaxis 0/861 (0%) 2/862 (0.2%)
    Pneumothorax 1/861 (0.1%) 1/862 (0.1%)
    Respiratory distress 0/861 (0%) 2/862 (0.2%)
    Aspiration 0/861 (0%) 1/862 (0.1%)
    Bronchiectasis 0/861 (0%) 1/862 (0.1%)
    Dyspnoea at rest 0/861 (0%) 1/862 (0.1%)
    Haemoptysis 0/861 (0%) 1/862 (0.1%)
    Hydrothorax 0/861 (0%) 1/862 (0.1%)
    Hypoxia 0/861 (0%) 1/862 (0.1%)
    Pleurisy 1/861 (0.1%) 0/862 (0%)
    Pleuritic pain 1/861 (0.1%) 0/862 (0%)
    Pneumothorax spontaneous 0/861 (0%) 1/862 (0.1%)
    Pulmonary arterial hypertension 1/861 (0.1%) 0/862 (0%)
    Respiratory acidosis 1/861 (0.1%) 0/862 (0%)
    Respiratory arrest 0/861 (0%) 1/862 (0.1%)
    Skin and subcutaneous tissue disorders
    Diabetic foot 5/861 (0.6%) 5/862 (0.6%)
    Decubitus ulcer 4/861 (0.5%) 1/862 (0.1%)
    Neuropathic ulcer 0/861 (0%) 2/862 (0.2%)
    Capillaritis 0/861 (0%) 1/862 (0.1%)
    Hidradenitis 1/861 (0.1%) 0/862 (0%)
    Pemphigoid 1/861 (0.1%) 0/862 (0%)
    Pruritus 0/861 (0%) 1/862 (0.1%)
    Rash 0/861 (0%) 1/862 (0.1%)
    Rash maculo-papular 0/861 (0%) 1/862 (0.1%)
    Rash scarlatiniform 1/861 (0.1%) 0/862 (0%)
    Skin ulcer 0/861 (0%) 1/862 (0.1%)
    Vascular disorders
    Hypertension 8/861 (0.9%) 9/862 (1%)
    Deep vein thrombosis 5/861 (0.6%) 7/862 (0.8%)
    Hypertensive emergency 4/861 (0.5%) 8/862 (0.9%)
    Hypertensive urgency 4/861 (0.5%) 5/862 (0.6%)
    Hypotension 6/861 (0.7%) 2/862 (0.2%)
    Hypertensive crisis 0/861 (0%) 6/862 (0.7%)
    Peripheral arterial occlusive disease 3/861 (0.3%) 3/862 (0.3%)
    Aortic stenosis 2/861 (0.2%) 2/862 (0.2%)
    Peripheral artery thrombosis 4/861 (0.5%) 0/862 (0%)
    Peripheral ischaemia 4/861 (0.5%) 0/862 (0%)
    Orthostatic hypotension 2/861 (0.2%) 1/862 (0.1%)
    Peripheral vascular disorder 1/861 (0.1%) 2/862 (0.2%)
    Arteriosclerosis 1/861 (0.1%) 1/862 (0.1%)
    Hypovolaemic shock 2/861 (0.2%) 0/862 (0%)
    Steal syndrome 1/861 (0.1%) 1/862 (0.1%)
    Venous thrombosis limb 0/861 (0%) 2/862 (0.2%)
    Accelerated hypertension 0/861 (0%) 1/862 (0.1%)
    Aortic aneurysm 1/861 (0.1%) 0/862 (0%)
    Axillary vein thrombosis 0/861 (0%) 1/862 (0.1%)
    Extremity necrosis 0/861 (0%) 1/862 (0.1%)
    Haematoma 1/861 (0.1%) 0/862 (0%)
    Lymphocele 0/861 (0%) 1/862 (0.1%)
    Lymphorrhoea 1/861 (0.1%) 0/862 (0%)
    Malignant hypertension 1/861 (0.1%) 0/862 (0%)
    Shock haemorrhagic 1/861 (0.1%) 0/862 (0%)
    Subclavian vein stenosis 1/861 (0.1%) 0/862 (0%)
    Vascular rupture 1/861 (0.1%) 0/862 (0%)
    Vascular stenosis 0/861 (0%) 1/862 (0.1%)
    Other (Not Including Serious) Adverse Events
    Vadadustat Darbepoetin Alfa
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 482/861 (56%) 436/862 (50.6%)
    Gastrointestinal disorders
    Diarrhoea 117/861 (13.6%) 76/862 (8.8%)
    Nausea 73/861 (8.5%) 57/862 (6.6%)
    Constipation 44/861 (5.1%) 38/862 (4.4%)
    General disorders
    Oedema peripheral 84/861 (9.8%) 85/862 (9.9%)
    Infections and infestations
    Urinary tract infection 93/861 (10.8%) 113/862 (13.1%)
    Nasopharyngitis 53/861 (6.2%) 61/862 (7.1%)
    Upper respiratory tract infection 55/861 (6.4%) 44/862 (5.1%)
    Bronchitis 44/861 (5.1%) 32/862 (3.7%)
    Injury, poisoning and procedural complications
    Fall 64/861 (7.4%) 53/862 (6.1%)
    Metabolism and nutrition disorders
    Hyperkalaemia 71/861 (8.2%) 78/862 (9%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 42/861 (4.9%) 48/862 (5.6%)
    Nervous system disorders
    Headache 22/861 (2.6%) 45/862 (5.2%)
    Vascular disorders
    Hypertension 120/861 (13.9%) 123/862 (14.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There IS 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 Clinical Trial Information Desk
    Organization Akebia Therapeutics, Inc.
    Phone +1 617-844-6128
    Email trials@akebia.com
    Responsible Party:
    Akebia Therapeutics
    ClinicalTrials.gov Identifier:
    NCT02680574
    Other Study ID Numbers:
    • AKB-6548-CI-0015
    • 2015-004774-14
    First Posted:
    Feb 11, 2016
    Last Update Posted:
    Jun 27, 2022
    Last Verified:
    Jun 1, 2022