Trial Outcomes & Findings for Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD) (NCT NCT02680574)

Last Updated: 2022-06-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1725 participants

Primary outcome timeframe

Baseline; Weeks 24 to 36

Results posted on

2022-06-27

Participant Flow

A total of 2961 participants were screened for entry into the study. Of these, 1725 participants were enrolled and randomized into the study.

Participant milestones

Participant milestones
Measure	Vadadustat 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.	Darbepoetin Alfa 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.
Overall Study STARTED	862	863
Overall Study COMPLETED	704	711
Overall Study NOT COMPLETED	158	152

Reasons for withdrawal

Reasons for withdrawal
Measure	Vadadustat 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.	Darbepoetin Alfa 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.
Overall Study Death	137	137
Overall Study Withdrawal by Subject	17	9
Overall Study Lost to Follow-up	4	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vadadustat n=862 Participants 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.	Darbepoetin Alfa n=863 Participants 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 n=1725 Participants Total of all reporting groups
Age, Continuous	67.3 Years STANDARD_DEVIATION 13.14 • n=5 Participants	66.5 Years STANDARD_DEVIATION 13.52 • n=7 Participants	66.9 Years STANDARD_DEVIATION 13.33 • n=5 Participants
Sex: Female, Male Female	468 Participants n=5 Participants	488 Participants n=7 Participants	956 Participants n=5 Participants
Sex: Female, Male Male	394 Participants n=5 Participants	375 Participants n=7 Participants	769 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	32 Participants n=5 Participants	26 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized Asian	62 Participants n=5 Participants	55 Participants n=7 Participants	117 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	93 Participants n=5 Participants	131 Participants n=7 Participants	224 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White	631 Participants n=5 Participants	603 Participants n=7 Participants	1234 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Reported as Other	25 Participants n=5 Participants	32 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Average hemoglobin	10.423 Grams per deciliter (g/dL) STANDARD_DEVIATION 0.8871 • n=5 Participants	10.390 Grams per deciliter (g/dL) STANDARD_DEVIATION 0.9430 • n=7 Participants	10.406 Grams per deciliter (g/dL) STANDARD_DEVIATION 0.9154 • n=5 Participants
Mean estimated glomerular filtration rate	22.6 mL/min/1.73m^2 STANDARD_DEVIATION 11.64 • n=5 Participants	22.8 mL/min/1.73m^2 STANDARD_DEVIATION 12.04 • n=7 Participants	22.7 mL/min/1.73m^2 STANDARD_DEVIATION 11.84 • n=5 Participants
Number of Participants with History of Diabetes	444 Participants n=5 Participants	432 Participants n=7 Participants	876 Participants n=5 Participants
Number of Participants with NYHA Functional Classification of Heart Failure NYHA Class 0	610 Participants n=5 Participants	595 Participants n=7 Participants	1205 Participants n=5 Participants
Number of Participants with NYHA Functional Classification of Heart Failure NYHA Class I	108 Participants n=5 Participants	108 Participants n=7 Participants	216 Participants n=5 Participants
Number of Participants with NYHA Functional Classification of Heart Failure NYHA Class II	113 Participants n=5 Participants	122 Participants n=7 Participants	235 Participants n=5 Participants
Number of Participants with NYHA Functional Classification of Heart Failure NYHA Class III	29 Participants n=5 Participants	36 Participants n=7 Participants	65 Participants n=5 Participants
Number of Participants with NYHA Functional Classification of Heart Failure NYHA Class IV	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Number of Participants with NYHA Functional Classification of Heart Failure NYHA Class Missing	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Number of Participants with Any History of Heart Failure Yes	44 Participants n=5 Participants	52 Participants n=7 Participants	96 Participants n=5 Participants
Number of Participants with Any History of Heart Failure No	613 Participants n=5 Participants	595 Participants n=7 Participants	1208 Participants n=5 Participants
Number of Participants with Any History of Heart Failure Missing	205 Participants n=5 Participants	216 Participants n=7 Participants	421 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline; Weeks 24 to 36

Population: Randomized Population: All participants randomized. Analyses of this population were based on the randomized treatment.

Outcome measures

Outcome measures
Measure	Vadadustat n=862 Participants 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.	Darbepoetin Alfa n=863 Participants 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.
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)	0.41 Grams per deciliter (g/dL) Standard Error 0.036	0.42 Grams per deciliter (g/dL) Standard Error 0.037

PRIMARY outcome

Timeframe: Up to Week 208

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Vadadustat n=168 Participants 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.	Darbepoetin Alfa n=152 Participants 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.
Median Time to First Major Adverse Cardiovascular Event (MACE)	53.21 Weeks Interval 30.64 to 81.43	58.00 Weeks Interval 31.07 to 99.21

SECONDARY outcome

Timeframe: Baseline; Weeks 40 to 52

Population: Randomized Population. Analyses of this population were based on the randomized treatment.

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.

Outcome measures

Outcome measures
Measure	Vadadustat n=862 Participants 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.	Darbepoetin Alfa n=863 Participants 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.
Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)	0.43 g/dL Standard Error 0.044	0.44 g/dL Standard Error 0.044

SECONDARY outcome

Timeframe: Up to Week 208

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Vadadustat n=197 Participants 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.	Darbepoetin Alfa n=195 Participants 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.
Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis	48.29 Weeks Interval 22.71 to 72.71	49.29 Weeks Interval 20.14 to 86.43

SECONDARY outcome

Timeframe: Up to Week 208

Population: Safety Population (PRO2TECT). Only those participants with cardiovascular MACE events were analyzed for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Vadadustat n=89 Participants 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.	Darbepoetin Alfa n=83 Participants 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.
Median Time to First Cardiovascular MACE	45.57 Weeks Interval 20.14 to 67.57	50.29 Weeks Interval 18.29 to 83.29

SECONDARY outcome

Timeframe: Up to Week 208

Population: Safety Population (PRO2TECT). Only those participants with cardiovascular death were analyzed for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Vadadustat n=56 Participants 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.	Darbepoetin Alfa n=66 Participants 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.
Median Time to First Cardiovascular Death	48.29 Weeks Interval 29.5 to 69.14	54.21 Weeks Interval 30.71 to 94.14

SECONDARY outcome

Timeframe: Up to Week 208

Population: Safety Population (PRO2TECT). Only those participants with all-cause mortality were analyzed for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Vadadustat n=139 Participants 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.	Darbepoetin Alfa n=139 Participants 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.
Median Time to First All-cause Mortality	57.71 Weeks Interval 35.29 to 87.0	62.14 Weeks Interval 34.14 to 111.57

Serious events: 504 serious events

Other events: 482 other events

Deaths: 139 deaths

Darbepoetin Alfa

Serious events: 488 serious events

Other events: 436 other events

Deaths: 139 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Vadadustat n=861 participants at risk 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.	Darbepoetin Alfa n=862 participants at risk 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.
Vascular disorders Hypertension	13.9% 120/861 • Up to 208 weeks 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.	14.3% 123/862 • Up to 208 weeks 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.
Infections and infestations Urinary tract infection	10.8% 93/861 • Up to 208 weeks 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.	13.1% 113/862 • Up to 208 weeks 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.
Gastrointestinal disorders Diarrhoea	13.6% 117/861 • Up to 208 weeks 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.	8.8% 76/862 • Up to 208 weeks 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.
General disorders Oedema peripheral	9.8% 84/861 • Up to 208 weeks 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.	9.9% 85/862 • Up to 208 weeks 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.
Metabolism and nutrition disorders Hyperkalaemia	8.2% 71/861 • Up to 208 weeks 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.	9.0% 78/862 • Up to 208 weeks 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.
Gastrointestinal disorders Nausea	8.5% 73/861 • Up to 208 weeks 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.	6.6% 57/862 • Up to 208 weeks 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.
Injury, poisoning and procedural complications Fall	7.4% 64/861 • Up to 208 weeks 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.	6.1% 53/862 • Up to 208 weeks 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.
Infections and infestations Nasopharyngitis	6.2% 53/861 • Up to 208 weeks 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.	7.1% 61/862 • Up to 208 weeks 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.
Infections and infestations Upper respiratory tract infection	6.4% 55/861 • Up to 208 weeks 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.	5.1% 44/862 • Up to 208 weeks 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.
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 42/861 • Up to 208 weeks 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.	5.6% 48/862 • Up to 208 weeks 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.
Gastrointestinal disorders Constipation	5.1% 44/861 • Up to 208 weeks 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.	4.4% 38/862 • Up to 208 weeks 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.
Infections and infestations Bronchitis	5.1% 44/861 • Up to 208 weeks 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.	3.7% 32/862 • Up to 208 weeks 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.
Nervous system disorders Headache	2.6% 22/861 • Up to 208 weeks 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.	5.2% 45/862 • Up to 208 weeks 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.

Additional Information

Clinical Trial Information Desk

Akebia Therapeutics, Inc.

Phone: +1 617-844-6128

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place