Trial Outcomes & Findings for 20-Week Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia (NCT NCT01906489)

Results Overview

Hemoglobin (Hgb) response was defined as participants with mean Hgb ≥11.0 grams per deciliter (g/dL) (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving Erythropoiesis-Stimulating Agents (ESA) or transfusion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

210 participants

Primary outcome timeframe

Weeks 19 and 20

Results posted on

2022-07-21

Participant Flow

A total of 210 participants entered the study and 209 were randomized in a 2:1 ratio to receive Vadadustat or Placebo. However, 1 participant received Placebo in error.

Participant milestones

Participant milestones
Measure	Vadadustat Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo Participants received matching Placebo, as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Overall Study STARTED	138	72
Overall Study COMPLETED	112	63
Overall Study NOT COMPLETED	26	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Vadadustat Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo Participants received matching Placebo, as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Overall Study Adverse Event	10	3
Overall Study Worsening of CKD	6	4
Overall Study Withdrawal by Subject	5	0
Overall Study Worsening of Anemia	1	0
Overall Study Protocol Violation	0	1
Overall Study Non- Compliance	1	0
Overall Study Sponsor Decision	1	0
Overall Study Lost to Follow-up	1	1
Overall Study Other	1	0

Baseline Characteristics

20-Week Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vadadustat n=138 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants received matching Placebo, as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.	Total n=210 Participants Total of all reporting groups
Age, Continuous	66.6 years STANDARD_DEVIATION 9.97 • n=5 Participants	65.9 years STANDARD_DEVIATION 12.33 • n=7 Participants	66.4 years STANDARD_DEVIATION 10.81 • n=5 Participants
Sex: Female, Male Female	81 Participants n=5 Participants	34 Participants n=7 Participants	115 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	38 Participants n=7 Participants	95 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	49 Participants n=5 Participants	19 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) White	83 Participants n=5 Participants	49 Participants n=7 Participants	132 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 19 and 20

Population: Per Protocol (PP) Population: participants in modified intent-to-treat (MITT) Population who had completed the study and had efficacy data through Week 20, had a study medication compliance of ≥ 80%, and did not have any protocol deviations. Only participants with available data were analyzed.

Hemoglobin (Hgb) response was defined as participants with mean Hgb ≥11.0 grams per deciliter (g/dL) (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving Erythropoiesis-Stimulating Agents (ESA) or transfusion.

Outcome measures

Outcome measures
Measure	Vadadustat n=102 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=58 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Achieving a Successful Hemoglobin Response	54.9 Percentage of participants	10.3 Percentage of participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: Modified Intent-to-Treat (MITT) Population: all randomized participants who received at least one dose of study medication and had a Baseline (either screening or Baseline for both Hgb and RBC count) and at least one post-Baseline measurement for both Hgb and RBC. Only participants with available data were analyzed.

Participants who have experienced an excursion in Hgb to ≥13.0 g/dL at any time during the study were considered as "failures". Data was presented for failures.

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study	59.6 Percentage of participants	88.9 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 19 and 20

Population: MITT Population. Only participants with available data were analyzed.

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing). Analysis of this secondary outcome measure is a reanalysis of the primary outcome measure whereby the response was determined solely by the Hgb value and receiving rescue therapy did not make the participant a failure.

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value	44.9 Percentage of participants	13.9 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 19 and 20

Population: MITT Population. Only participants with available data were analyzed.

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Treatment Naïve group, defined as participants who had never received treatment with an ESA and who had a screening Hgb level of ≤10.5 g/dL.

Outcome measures

Outcome measures
Measure	Vadadustat n=68 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=38 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group	50 Percentage of participants	7.9 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 19 and 20

Population: MITT Population. Only participants with available data were analyzed.

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Previously Treated group, defined as participants who had previously received ≥1 dose of an ESA, had been off of ESA therapy for ≥11 weeks at the time of screening, and had a screening Hgb level of ≤10.5 g/dL.

Outcome measures

Outcome measures
Measure	Vadadustat n=41 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=21 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group	41.5 Percentage of participants	19 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 19 and 20

Population: MITT Population. Only participants with available data were analyzed.

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Actively Treated group, defined as participants who had been actively treated with an ESA for a minimum of 4 months before screening, had received at least 2 doses within the last 4 months, had received their last dose within 6 weeks before screening, and had a screening Hgb level ≥9.5 g/dL and ≤12.0 g/dL.

Outcome measures

Outcome measures
Measure	Vadadustat n=27 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=13 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group	33.3 Percentage of participants	7.7 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 19 and 20

Population: MITT Population. Only participants with available data were analyzed.

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Analysis of this secondary outcome measure was performed in the mITT population.

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population	44.1 Percentage of participants	11.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected to assess Hgb. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hgb concentration increased.

Outcome measures

Outcome measures
Measure	Vadadustat n=135 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Change From Baseline in Hemoglobin Baseline	9.94 g/dL Standard Deviation 0.861	9.96 g/dL Standard Deviation 0.790
Change From Baseline in Hemoglobin Week 2	0.1 g/dL Standard Deviation 0.756	-0.22 g/dL Standard Deviation 0.564
Change From Baseline in Hemoglobin Week 4	0.39 g/dL Standard Deviation 0.868	-0.25 g/dL Standard Deviation 0.679
Change From Baseline in Hemoglobin Week 6	0.63 g/dL Standard Deviation 1.059	-0.41 g/dL Standard Deviation 0.835
Change From Baseline in Hemoglobin Week 8	0.69 g/dL Standard Deviation 1.087	-0.4 g/dL Standard Deviation 0.878
Change From Baseline in Hemoglobin Week 12	0.9 g/dL Standard Deviation 1.066	-0.2 g/dL Standard Deviation 0.864
Change From Baseline in Hemoglobin Week 16	0.76 g/dL Standard Deviation 1.055	-0.18 g/dL Standard Deviation 0.963
Change From Baseline in Hemoglobin Week 19	0.73 g/dL Standard Deviation 1.063	-0.16 g/dL Standard Deviation 0.926
Change From Baseline in Hemoglobin Week 20	0.88 g/dL Standard Deviation 1.161	-0.08 g/dL Standard Deviation 0.933

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected at indicated time points for analysis of hemoglobin

Outcome measures

Outcome measures
Measure	Vadadustat n=135 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Absolute Values of Hemoglobin Week 2	10.02 g/dL Standard Deviation 0.909	9.74 g/dL Standard Deviation 0.714
Absolute Values of Hemoglobin Baseline	9.94 g/dL Standard Deviation 0.861	9.96 g/dL Standard Deviation 0.79
Absolute Values of Hemoglobin Week 4	10.35 g/dL Standard Deviation 0.979	9.7 g/dL Standard Deviation 0.733
Absolute Values of Hemoglobin Week 6	10.61 g/dL Standard Deviation 0.996	9.6 g/dL Standard Deviation 0.758
Absolute Values of Hemoglobin Week 8	10.66 g/dL Standard Deviation 0.987	9.6 g/dL Standard Deviation 0.848
Absolute Values of Hemoglobin Week 12	10.87 g/dL Standard Deviation 0.958	9.82 g/dL Standard Deviation 0.682
Absolute Values of Hemoglobin Week 16	10.79 g/dL Standard Deviation 0.895	9.83 g/dL Standard Deviation 0.841
Absolute Values of Hemoglobin Week 19	10.74 g/dL Standard Deviation 0.881	9.93 g/dL Standard Deviation 0.897
Absolute Values of Hemoglobin Week 20	10.88 g/dL Standard Deviation 1.002	9.93 g/dL Standard Deviation 0.859

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected to assess Hematocrit. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hematocrit concentration increased.

Outcome measures

Outcome measures
Measure	Vadadustat n=135 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Change From Baseline in Hematocrit Baseline	30.4 Percentage of red blood cells in blood Standard Deviation 2.96	30.3 Percentage of red blood cells in blood Standard Deviation 2.90
Change From Baseline in Hematocrit Week 2	0.8 Percentage of red blood cells in blood Standard Deviation 2.46	-0.6 Percentage of red blood cells in blood Standard Deviation 1.97
Change From Baseline in Hematocrit Week 4	2 Percentage of red blood cells in blood Standard Deviation 2.87	-0.5 Percentage of red blood cells in blood Standard Deviation 2.33
Change From Baseline in Hematocrit Week 6	2.5 Percentage of red blood cells in blood Standard Deviation 3.55	-1 Percentage of red blood cells in blood Standard Deviation 2.87
Change From Baseline in Hematocrit Week 8	2.7 Percentage of red blood cells in blood Standard Deviation 3.44	-1 Percentage of red blood cells in blood Standard Deviation 3.15
Change From Baseline in Hematocrit Week 12	3 Percentage of red blood cells in blood Standard Deviation 3.5	-0.3 Percentage of red blood cells in blood Standard Deviation 2.95
Change From Baseline in Hematocrit Week 16	3.3 Percentage of red blood cells in blood Standard Deviation 3.48	-0.1 Percentage of red blood cells in blood Standard Deviation 3.24
Change From Baseline in Hematocrit Week 19	3.1 Percentage of red blood cells in blood Standard Deviation 3.51	0 Percentage of red blood cells in blood Standard Deviation 3.19
Change From Baseline in Hematocrit Week 20	3 Percentage of red blood cells in blood Standard Deviation 3.8	0.1 Percentage of red blood cells in blood Standard Deviation 3.13

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected at indicated time points for analysis of Hematocrit.

Outcome measures

Outcome measures
Measure	Vadadustat n=135 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Absolute Values of Hematocrit Baseline	30.4 Percentage of red blood cells in blood Standard Deviation 2.96	30.3 Percentage of red blood cells in blood Standard Deviation 2.9
Absolute Values of Hematocrit Week 2	31.2 Percentage of red blood cells in blood Standard Deviation 3.06	29.7 Percentage of red blood cells in blood Standard Deviation 2.62
Absolute Values of Hematocrit Week 4	32.4 Percentage of red blood cells in blood Standard Deviation 3.17	29.7 Percentage of red blood cells in blood Standard Deviation 2.72
Absolute Values of Hematocrit Week 6	33.1 Percentage of red blood cells in blood Standard Deviation 3.21	29.4 Percentage of red blood cells in blood Standard Deviation 2.46
Absolute Values of Hematocrit Week 8	33.2 Percentage of red blood cells in blood Standard Deviation 3.05	29.3 Percentage of red blood cells in blood Standard Deviation 3.05
Absolute Values of Hematocrit Week 12	33.5 Percentage of red blood cells in blood Standard Deviation 3.19	30.2 Percentage of red blood cells in blood Standard Deviation 2.05
Absolute Values of Hematocrit Week 16	34 Percentage of red blood cells in blood Standard Deviation 3.02	30.3 Percentage of red blood cells in blood Standard Deviation 2.87
Absolute Values of Hematocrit Week 19	33.7 Percentage of red blood cells in blood Standard Deviation 2.83	30.7 Percentage of red blood cells in blood Standard Deviation 2.83
Absolute Values of Hematocrit Week 20	33.6 Percentage of red blood cells in blood Standard Deviation 3.19	30.4 Percentage of red blood cells in blood Standard Deviation 2.7

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected to assess red blood cell count. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated red blood cell count increased.

Outcome measures

Outcome measures
Measure	Vadadustat n=135 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Change From Baseline in Red Blood Cell Count Baseline	3.38 10^6 cells per microliter Standard Deviation 0.402	3.34 10^6 cells per microliter Standard Deviation 0.322
Change From Baseline in Red Blood Cell Count Week 2	0.02 10^6 cells per microliter Standard Deviation 0.243	-0.08 10^6 cells per microliter Standard Deviation 0.212
Change From Baseline in Red Blood Cell Count Week 4	0.12 10^6 cells per microliter Standard Deviation 0.277	-0.08 10^6 cells per microliter Standard Deviation 0.222
Change From Baseline in Red Blood Cell Count Week 6	0.18 10^6 cells per microliter Standard Deviation 0.346	-0.14 10^6 cells per microliter Standard Deviation 0.276
Change From Baseline in Red Blood Cell Count Week 8	0.23 10^6 cells per microliter Standard Deviation 0.351	-0.14 10^6 cells per microliter Standard Deviation 0.32
Change From Baseline in Red Blood Cell Count Week 12	0.3 10^6 cells per microliter Standard Deviation 0.357	-0.08 10^6 cells per microliter Standard Deviation 0.29
Change From Baseline in Red Blood Cell Count Week 16	0.28 10^6 cells per microliter Standard Deviation 0.363	-0.06 10^6 cells per microliter Standard Deviation 0.331
Change From Baseline in Red Blood Cell Count Week 19	0.26 10^6 cells per microliter Standard Deviation 0.374	-0.04 10^6 cells per microliter Standard Deviation 0.319
Change From Baseline in Red Blood Cell Count Week 20	0.3 10^6 cells per microliter Standard Deviation 0.411	-0.01 10^6 cells per microliter Standard Deviation 0.314

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected at indicated time points for analysis of red blood cell count.

Outcome measures

Outcome measures
Measure	Vadadustat n=135 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Absolute Values of Red Blood Cell Count Baseline	3.38 10^6 cells per microliter Standard Deviation 0.402	3.34 10^6 cells per microliter Standard Deviation 0.322
Absolute Values of Red Blood Cell Count Week 2	3.39 10^6 cells per microliter Standard Deviation 0.418	3.25 10^6 cells per microliter Standard Deviation 0.321
Absolute Values of Red Blood Cell Count Week 4	3.51 10^6 cells per microliter Standard Deviation 0.409	3.24 10^6 cells per microliter Standard Deviation 0.317
Absolute Values of Red Blood Cell Count Week 6	3.57 10^6 cells per microliter Standard Deviation 0.412	3.2 10^6 cells per microliter Standard Deviation 0.321
Absolute Values of Red Blood Cell Count Week 8	3.61 10^6 cells per microliter Standard Deviation 0.421	3.21 10^6 cells per microliter Standard Deviation 0.377
Absolute Values of Red Blood Cell Count Week 12	3.68 10^6 cells per microliter Standard Deviation 0.457	3.27 10^6 cells per microliter Standard Deviation 0.295
Absolute Values of Red Blood Cell Count Week 16	3.69 10^6 cells per microliter Standard Deviation 0.44	3.29 10^6 cells per microliter Standard Deviation 0.343
Absolute Values of Red Blood Cell Count Week 19	3.67 10^6 cells per microliter Standard Deviation 0.415	3.32 10^6 cells per microliter Standard Deviation 0.332
Absolute Values of Red Blood Cell Count Week 20	3.7 10^6 cells per microliter Standard Deviation 0.453	3.33 10^6 cells per microliter Standard Deviation 0.318

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected to assess reticulocyte count. Baseline was defined as mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated reticulocyte count increased.

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Change From Baseline in Reticulocyte Count Week 12	-0.12 10^6 cells per microliter Standard Deviation 0.742	0.02 10^6 cells per microliter Standard Deviation 0.639
Change From Baseline in Reticulocyte Count Week 16	0.03 10^6 cells per microliter Standard Deviation 0.678	-0.03 10^6 cells per microliter Standard Deviation 0.659
Change From Baseline in Reticulocyte Count Baseline	2.12 10^6 cells per microliter Standard Deviation 0.858	1.97 10^6 cells per microliter Standard Deviation 0.816
Change From Baseline in Reticulocyte Count Week 2	0.61 10^6 cells per microliter Standard Deviation 0.778	-0.07 10^6 cells per microliter Standard Deviation 0.532
Change From Baseline in Reticulocyte Count Week 4	0.29 10^6 cells per microliter Standard Deviation 0.686	0.06 10^6 cells per microliter Standard Deviation 0.485
Change From Baseline in Reticulocyte Count Week 6	0.19 10^6 cells per microliter Standard Deviation 0.749	0.08 10^6 cells per microliter Standard Deviation 0.549
Change From Baseline in Reticulocyte Count Week 8	-0.08 10^6 cells per microliter Standard Deviation 0.737	0.06 10^6 cells per microliter Standard Deviation 0.665
Change From Baseline in Reticulocyte Count Week 19	0.07 10^6 cells per microliter Standard Deviation 0.88	-0.05 10^6 cells per microliter Standard Deviation 0.672
Change From Baseline in Reticulocyte Count Week 20	0.03 10^6 cells per microliter Standard Deviation 0.666	0.12 10^6 cells per microliter Standard Deviation 0.786

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

Population: MITT Population. Only participants with available data were analyzed.

Blood samples were collected at indicated time points for analysis of reticulocyte count.

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Absolute Values of Reticulocyte Count Baseline	2.12 10^6 cells per microliter Standard Deviation 0.858	1.97 10^6 cells per microliter Standard Deviation 0.816
Absolute Values of Reticulocyte Count Week 2	2.74 10^6 cells per microliter Standard Deviation 1.069	1.91 10^6 cells per microliter Standard Deviation 0.727
Absolute Values of Reticulocyte Count Week 4	2.44 10^6 cells per microliter Standard Deviation 0.962	2.06 10^6 cells per microliter Standard Deviation 0.731
Absolute Values of Reticulocyte Count Week 6	2.32 10^6 cells per microliter Standard Deviation 0.996	2.07 10^6 cells per microliter Standard Deviation 0.897
Absolute Values of Reticulocyte Count Week 8	2.05 10^6 cells per microliter Standard Deviation 0.884	2.09 10^6 cells per microliter Standard Deviation 0.85
Absolute Values of Reticulocyte Count Week 12	2.02 10^6 cells per microliter Standard Deviation 0.959	2 10^6 cells per microliter Standard Deviation 0.846
Absolute Values of Reticulocyte Count Week 16	2.13 10^6 cells per microliter Standard Deviation 0.992	1.96 10^6 cells per microliter Standard Deviation 0.83
Absolute Values of Reticulocyte Count Week 19	2.21 10^6 cells per microliter Standard Deviation 1.297	1.92 10^6 cells per microliter Standard Deviation 0.77
Absolute Values of Reticulocyte Count Week 20	2.17 10^6 cells per microliter Standard Deviation 0.954	2.1 10^6 cells per microliter Standard Deviation 0.88

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: MITT Population. Only participants with available data were analyzed.

Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Who Received ESA Rescue Epoetin Alfa	4.4 Percentage of participants	12.5 Percentage of participants
Percentage of Participants Who Received ESA Rescue Darbepoetin Alfa	0 Percentage of participants	4.2 Percentage of participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: MITT Population. Only participants with available data were analyzed.

Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

Outcome measures

Outcome measures
Measure	Vadadustat n=6 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=9 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Mean Number of ESA Rescue Doses Administered Per Participant Epoetin Alfa	1.7 Doses/participants Standard Deviation 1.63	2.8 Doses/participants Standard Deviation 1.79
Mean Number of ESA Rescue Doses Administered Per Participant Darbepoetin Alfa	—	4.3 Doses/participants Standard Deviation 2.52

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: MITT Population. Only participants with available data were analyzed.

Participants were administered packed red blood cell transfusion as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue	0 Percentage of participants	1.4 Percentage of participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: MITT Population. Only participants who received transfusion rescue were analyzed.

Participants were administered packed red blood cells as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

Outcome measures

Outcome measures
Measure	Vadadustat Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=1 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Number of Packed Red Blood Cell Transfusion Administered Per Participant	—	1.0 Units of blood per participant Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: MITT Population. Only participants with available data were analyzed.

Rescue therapy was defined as red blood cell transfusion or ESA administration in participants meeting Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

Outcome measures

Outcome measures
Measure	Vadadustat n=136 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Time to First Transfusion or ESA Rescue Medication Intake	21.6 Weeks Standard Deviation 6.08	21.2 Weeks Standard Deviation 5.71

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received at least one dose of study medication

An Adverse Event (AE) was defined as any untoward medical occurrence, signs, symptoms, disease, or laboratory or physiological observations occurring in a participant administered with drug, regardless of a causal relationship with that treatment or usage. This also included all suspected adverse medication reactions, reactions from medication overdose, abuse, withdrawal, sensitivity, toxicity, unrelated illnesses, including worsening a pre-existing condition, injury, or accidents. Serious Adverse Events (SAEs) was defined as any life-threatening condition; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or death.

Outcome measures

Outcome measures
Measure	Vadadustat n=138 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) TEAEs	58 Participants	29 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) Treatment-emergent SAEs	33 Participants	11 Participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: ITT Population

Parameters assessed for laboratory values included hematology, serum chemistry, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant changes.

Outcome measures

Outcome measures
Measure	Vadadustat n=138 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values Hematology	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values Serum chemistry	1 Participants	0 Participants
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values Urinalysis	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: ITT Population

Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing laboratory results for clinically significant changes.

Outcome measures

Outcome measures
Measure	Vadadustat n=138 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: ITT Population

A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance.

Outcome measures

Outcome measures
Measure	Vadadustat n=138 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: ITT Population

A Baseline physical examination was performed at screening. Otherwise, abbreviated physical examinations were conducted and were to include heart, lung, and abdomen. The investigator was responsible for reviewing laboratory results for clinically significant changes.

Outcome measures

Outcome measures
Measure	Vadadustat n=138 Participants Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 Participants Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings	0 Participants	0 Participants

Serious events: 33 serious events

Other events: 58 other events

Deaths: 3 deaths

Placebo

Serious events: 11 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Vadadustat n=138 participants at risk Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	Placebo n=72 participants at risk Participants received matching Placebo, as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
Gastrointestinal disorders Nausea	10.1% 14/138 • From the start of treatment (Day 1) up to 24 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.	4.2% 3/72 • From the start of treatment (Day 1) up to 24 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.
Gastrointestinal disorders Diarrhoea	10.1% 14/138 • From the start of treatment (Day 1) up to 24 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.	4.2% 3/72 • From the start of treatment (Day 1) up to 24 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.
Gastrointestinal disorders Constipation	3.6% 5/138 • From the start of treatment (Day 1) up to 24 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.	5.6% 4/72 • From the start of treatment (Day 1) up to 24 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.
General disorders Fatigue	8.0% 11/138 • From the start of treatment (Day 1) up to 24 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.	6.9% 5/72 • From the start of treatment (Day 1) up to 24 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.
General disorders Oedema peripheral	7.2% 10/138 • From the start of treatment (Day 1) up to 24 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.	9.7% 7/72 • From the start of treatment (Day 1) up to 24 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.
Infections and infestations Upper Respiratory Tract Infection	1.4% 2/138 • From the start of treatment (Day 1) up to 24 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.	6.9% 5/72 • From the start of treatment (Day 1) up to 24 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.
Infections and infestations Urinary tract infection	5.8% 8/138 • From the start of treatment (Day 1) up to 24 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.	8.3% 6/72 • From the start of treatment (Day 1) up to 24 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.
Nervous system disorders Headache	5.8% 8/138 • From the start of treatment (Day 1) up to 24 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.	2.8% 2/72 • From the start of treatment (Day 1) up to 24 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.
Nervous system disorders Dizziness	5.1% 7/138 • From the start of treatment (Day 1) up to 24 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.	4.2% 3/72 • From the start of treatment (Day 1) up to 24 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.
Vascular disorders Hypertension	8.0% 11/138 • From the start of treatment (Day 1) up to 24 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.	2.8% 2/72 • From the start of treatment (Day 1) up to 24 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.
Vascular disorders Hypotension	4.3% 6/138 • From the start of treatment (Day 1) up to 24 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.	5.6% 4/72 • From the start of treatment (Day 1) up to 24 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.

Additional Information

Akebia Therapeutics

Phone: 617-844-6128

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER