Trial Outcomes & Findings for 16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis (NCT NCT02260193)

Last Updated: 2022-07-01

Results Overview

Change from pre-dose average was calculated by the mid-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

94 participants

Primary outcome timeframe

Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8

Results posted on

2022-07-01

Participant Flow

A total of 128 participants were screened, of which 94 participants were enrolled and randomized into the study.

Participant milestones

Participant milestones
Measure	Vadadustat 450 mg QD Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 300 mg Once Daily (QD) Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Overall Study STARTED	33	31	30
Overall Study COMPLETED	24	21	24
Overall Study NOT COMPLETED	9	10	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Vadadustat 450 mg QD Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 300 mg Once Daily (QD) Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Overall Study Lack of Efficacy	1	6	0
Overall Study Adverse Event	4	1	3
Overall Study Protocol Violation	4	0	0
Overall Study Withdrawal by Subject	0	2	3
Overall Study Kidney Transplantation	0	1	0

Baseline Characteristics

16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Total n=94 Participants Total of all reporting groups
Age, Continuous	55.5 Years STANDARD_DEVIATION 12.44 • n=113 Participants	59.4 Years STANDARD_DEVIATION 11.62 • n=163 Participants	57.8 Years STANDARD_DEVIATION 8.26 • n=160 Participants	57.6 Years STANDARD_DEVIATION 10.93 • n=483 Participants
Sex: Female, Male Female	13 Participants n=113 Participants	15 Participants n=163 Participants	12 Participants n=160 Participants	40 Participants n=483 Participants
Sex: Female, Male Male	17 Participants n=113 Participants	18 Participants n=163 Participants	19 Participants n=160 Participants	54 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=113 Participants	18 Participants n=163 Participants	15 Participants n=160 Participants	47 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=113 Participants	15 Participants n=163 Participants	16 Participants n=160 Participants	47 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=113 Participants	0 Participants n=163 Participants	1 Participants n=160 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=113 Participants	1 Participants n=163 Participants	2 Participants n=160 Participants	3 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=113 Participants	2 Participants n=163 Participants	0 Participants n=160 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Black or African American	6 Participants n=113 Participants	9 Participants n=163 Participants	9 Participants n=160 Participants	24 Participants n=483 Participants
Race (NIH/OMB) White	24 Participants n=113 Participants	21 Participants n=163 Participants	19 Participants n=160 Participants	64 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants

PRIMARY outcome

Timeframe: Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8

Population: Modified Intent-to-treat (MITT) Population: All participants who were assigned to study medication, received at least 1 dose of study medication, and had a pre-dose average and at least one post-baseline Hgb measurement. The primary analysis was performed in the MITT population using observed Hgb data without imputation for missing data.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average Pre-dose Average	10.43 Grams per deciliter (g/dL) Standard Deviation 0.645	10.55 Grams per deciliter (g/dL) Standard Deviation 0.577	10.52 Grams per deciliter (g/dL) Standard Deviation 0.534
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average Change from pre-dose average to the mid-study average	0.00 Grams per deciliter (g/dL) Standard Deviation 0.897	-0.29 Grams per deciliter (g/dL) Standard Deviation 0.970	-0.36 Grams per deciliter (g/dL) Standard Deviation 1.134

PRIMARY outcome

Timeframe: Pre-dose, Week 15, and Week 16

Population: MITT Population. The primary analysis was performed in the MITT population using observed Hgb data without imputation for missing data.

Change from pre-dose average was calculated by the end-of-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Pre-dose Average in Hgb Level to The End-of-study Average Pre-dose Average	10.43 g/dL Standard Deviation 0.645	10.55 g/dL Standard Deviation 0.577	10.52 g/dL Standard Deviation 0.534
Change From Pre-dose Average in Hgb Level to The End-of-study Average Change From Pre-dose average to The End-of-study Average	-0.03 g/dL Standard Deviation 0.902	-0.07 g/dL Standard Deviation 0.973	-0.14 g/dL Standard Deviation 1.123

PRIMARY outcome

Timeframe: Week 7, Week 8, Week 15, and Week 16

Population: MITT Population. The primary analysis was performed in the MITT population using observed Hgb data without imputation for missing data.

Change from mid-study average was calculated by the end-of-study average minus the mid-study average. The mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=28 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=28 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=26 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Mid-study Average in Hgb Level to The End-of-study Average Mid-study Average	10.41 g/dL Standard Deviation 0.834	10.26 g/dL Standard Deviation 1.167	10.19 g/dL Standard Deviation 0.950
Change From Mid-study Average in Hgb Level to The End-of-study Average Change From Mid-study Average to The End-of-study Average	-0.18 g/dL Standard Deviation 0.512	0.16 g/dL Standard Deviation 0.809	-0.07 g/dL Standard Deviation 0.611

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the three samples obtained prior to dosing.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Hgb Baseline	10.50 g/dL Standard Deviation 0.702	10.51 g/dL Standard Deviation 0.755	10.50 g/dL Standard Deviation 0.646
Change From Baseline in Hgb Change from Baseline to Week 4	-0.06 g/dL Standard Deviation 0.708	-0.21 g/dL Standard Deviation 0.814	-0.35 g/dL Standard Deviation 0.887
Change From Baseline in Hgb Change from Baseline to Week 8	-0.14 g/dL Standard Deviation 1.058	-0.39 g/dL Standard Deviation 1.201	-0.37 g/dL Standard Deviation 1.386
Change From Baseline in Hgb Change from Baseline to Week 12	0.02 g/dL Standard Deviation 0.995	-0.11 g/dL Standard Deviation 1.087	-0.06 g/dL Standard Deviation 1.210
Change From Baseline in Hgb Change from Baseline to Week 16	-0.03 g/dL Standard Deviation 0.946	-0.13 g/dL Standard Deviation 1.076	-0.06 g/dL Standard Deviation 1.146

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hematocrit was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Hematocrit Baseline	31.2 Percentage of red blood cells in blood Standard Deviation 2.58	31.6 Percentage of red blood cells in blood Standard Deviation 3.75	31.4 Percentage of red blood cells in blood Standard Deviation 2.75
Change From Baseline in Hematocrit Change from Baseline to Week 4	-0.4 Percentage of red blood cells in blood Standard Deviation 2.82	-1.4 Percentage of red blood cells in blood Standard Deviation 3.36	-0.7 Percentage of red blood cells in blood Standard Deviation 3.14
Change From Baseline in Hematocrit Change from Baseline to Week 8	-1.0 Percentage of red blood cells in blood Standard Deviation 3.87	-1.6 Percentage of red blood cells in blood Standard Deviation 4.73	-1.7 Percentage of red blood cells in blood Standard Deviation 4.43
Change From Baseline in Hematocrit Change from Baseline to Week 12	-0.2 Percentage of red blood cells in blood Standard Deviation 3.35	-0.8 Percentage of red blood cells in blood Standard Deviation 4.07	-0.1 Percentage of red blood cells in blood Standard Deviation 4.35
Change From Baseline in Hematocrit Change from Baseline to Week 16	-0.8 Percentage of red blood cells in blood Standard Deviation 3.26	-1.2 Percentage of red blood cells in blood Standard Deviation 4.19	-0.2 Percentage of red blood cells in blood Standard Deviation 3.67

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC Count was defined as the average of the three samples obtained prior to dosing.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Red Blood Cell (RBC) Count Baseline	3.34 10^6 cells per microliter Standard Deviation 0.278	3.49 10^6 cells per microliter Standard Deviation 0.446	3.49 10^6 cells per microliter Standard Deviation 0.385
Change From Baseline in Red Blood Cell (RBC) Count Change from Baseline to Week 4	-0.06 10^6 cells per microliter Standard Deviation 0.235	-0.11 10^6 cells per microliter Standard Deviation 0.346	-0.16 10^6 cells per microliter Standard Deviation 0.276
Change From Baseline in Red Blood Cell (RBC) Count Change from Baseline to Week 8	-0.09 10^6 cells per microliter Standard Deviation 0.357	-0.19 10^6 cells per microliter Standard Deviation 0.482	-0.16 10^6 cells per microliter Standard Deviation 0.432
Change From Baseline in Red Blood Cell (RBC) Count Change from Baseline to Week 12	-0.01 10^6 cells per microliter Standard Deviation 0.325	-0.14 10^6 cells per microliter Standard Deviation 0.473	-0.10 10^6 cells per microliter Standard Deviation 0.464
Change From Baseline in Red Blood Cell (RBC) Count Change from Baseline to Week 16	-0.05 10^6 cells per microliter Standard Deviation 0.309	-0.17 10^6 cells per microliter Standard Deviation 0.453	-0.08 10^6 cells per microliter Standard Deviation 0.412

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline absolute reticulocyte count was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Absolute Reticulocyte Count Baseline	0.0704 10^6 cells per microliter Standard Deviation 0.02548	0.0661 10^6 cells per microliter Standard Deviation 0.02300	0.0742 10^6 cells per microliter Standard Deviation 0.02777
Change From Baseline in Absolute Reticulocyte Count Change from Baseline to Week 4	-0.0059 10^6 cells per microliter Standard Deviation 0.02166	0.0023 10^6 cells per microliter Standard Deviation 0.02597	-0.0001 10^6 cells per microliter Standard Deviation 0.02813
Change From Baseline in Absolute Reticulocyte Count Change from Baseline to Week 8	-0.0054 10^6 cells per microliter Standard Deviation 0.01794	0.0041 10^6 cells per microliter Standard Deviation 0.02492	-0.0018 10^6 cells per microliter Standard Deviation 0.02571
Change From Baseline in Absolute Reticulocyte Count Change from Baseline to Week 12	0.0001 10^6 cells per microliter Standard Deviation 0.01592	0.0133 10^6 cells per microliter Standard Deviation 0.02734	0.0033 10^6 cells per microliter Standard Deviation 0.02479
Change From Baseline in Absolute Reticulocyte Count Change from Baseline to Week 16	-0.0009 10^6 cells per microliter Standard Deviation 0.02251	0.0048 10^6 cells per microliter Standard Deviation 0.02409	0.0040 10^6 cells per microliter Standard Deviation 0.02470

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline percent reticulocyte count was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Percent Reticulocyte Count Baseline	2.14 Percent change Standard Deviation 0.802	1.89 Percent change Standard Deviation 0.572	2.19 Percent change Standard Deviation 0.927
Change From Baseline in Percent Reticulocyte Count Change from Baseline to Week 4	-0.16 Percent change Standard Deviation 0.578	0.14 Percent change Standard Deviation 0.787	0.07 Percent change Standard Deviation 0.884
Change From Baseline in Percent Reticulocyte Count Change from Baseline to Week 8	-0.15 Percent change Standard Deviation 0.539	0.24 Percent change Standard Deviation 0.649	0.03 Percent change Standard Deviation 0.710
Change From Baseline in Percent Reticulocyte Count Change from Baseline to Week 12	-0.04 Percent change Standard Deviation 0.488	0.48 Percent change Standard Deviation 0.704	0.17 Percent change Standard Deviation 0.835
Change From Baseline in Percent Reticulocyte Count Change from Baseline to Week 16	-0.01 Percent change Standard Deviation 0.586	0.23 Percent change Standard Deviation 0.701	0.15 Percent change Standard Deviation 0.817

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 8, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline reticulocyte Hgb content was defined as the average of the three samples obtained prior to dosing.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Reticulocyte Hgb Content Baseline	32.39 μg/dL Standard Deviation 1.799	32.12 μg/dL Standard Deviation 1.675	30.99 μg/dL Standard Deviation 2.372
Change From Baseline in Reticulocyte Hgb Content Change from Baseline to Week 2	-0.13 μg/dL Standard Deviation 1.302	-0.03 μg/dL Standard Deviation 0.972	1.01 μg/dL Standard Deviation 1.621
Change From Baseline in Reticulocyte Hgb Content Change from Baseline to Week 4	-0.07 μg/dL Standard Deviation 0.859	-0.21 μg/dL Standard Deviation 1.023	1.02 μg/dL Standard Deviation 1.425
Change From Baseline in Reticulocyte Hgb Content Change from Baseline to Week 8	0.41 μg/dL Standard Deviation 1.159	-0.27 μg/dL Standard Deviation 1.308	1.13 μg/dL Standard Deviation 1.301
Change From Baseline in Reticulocyte Hgb Content Change from Baseline to Week 16	0.15 μg/dL Standard Deviation 1.026	0.58 μg/dL Standard Deviation 1.284	-0.18 μg/dL Standard Deviation 1.494

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Ferritin Baseline	762.88 Nanograms per milliliter (ng/mL) Standard Deviation 470.462	781.96 Nanograms per milliliter (ng/mL) Standard Deviation 465.148	807.75 Nanograms per milliliter (ng/mL) Standard Deviation 430.981
Change From Baseline in Ferritin Change from Baseline to Week 4	-48.80 Nanograms per milliliter (ng/mL) Standard Deviation 205.733	-61.21 Nanograms per milliliter (ng/mL) Standard Deviation 217.068	-10.29 Nanograms per milliliter (ng/mL) Standard Deviation 254.574
Change From Baseline in Ferritin Change from Baseline to Week 8	46.85 Nanograms per milliliter (ng/mL) Standard Deviation 529.361	-99.11 Nanograms per milliliter (ng/mL) Standard Deviation 240.436	-48.71 Nanograms per milliliter (ng/mL) Standard Deviation 289.063
Change From Baseline in Ferritin Change from Baseline to Week 12	-15.70 Nanograms per milliliter (ng/mL) Standard Deviation 316.387	-61.81 Nanograms per milliliter (ng/mL) Standard Deviation 302.719	0.92 Nanograms per milliliter (ng/mL) Standard Deviation 342.188
Change From Baseline in Ferritin Change from Baseline to Week 16	-56.67 Nanograms per milliliter (ng/mL) Standard Deviation 317.098	-115.36 Nanograms per milliliter (ng/mL) Standard Deviation 276.640	-39.03 Nanograms per milliliter (ng/mL) Standard Deviation 484.937

SECONDARY outcome

Timeframe: Baseline, Week 8, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline hepcidin was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Hepcidin Baseline	102.59 Nanograms per milliliter (ng/mL) Standard Deviation 58.938	119.61 Nanograms per milliliter (ng/mL) Standard Deviation 54.766	105.35 Nanograms per milliliter (ng/mL) Standard Deviation 46.805
Change From Baseline in Hepcidin Change from Baseline to Week 8	-6.46 Nanograms per milliliter (ng/mL) Standard Deviation 49.002	-27.80 Nanograms per milliliter (ng/mL) Standard Deviation 56.752	-9.14 Nanograms per milliliter (ng/mL) Standard Deviation 46.498
Change From Baseline in Hepcidin Change from Baseline to Week 16	-15.11 Nanograms per milliliter (ng/mL) Standard Deviation 46.526	-21.66 Nanograms per milliliter (ng/mL) Standard Deviation 45.381	-4.87 Nanograms per milliliter (ng/mL) Standard Deviation 50.379

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Total Iron-Binding Capacity (TIBC) Baseline	204.5 Micrograms per deciliter (μg/mL) Standard Deviation 39.72	196.7 Micrograms per deciliter (μg/mL) Standard Deviation 29.42	188.8 Micrograms per deciliter (μg/mL) Standard Deviation 32.28
Change From Baseline in Total Iron-Binding Capacity (TIBC) Change from Baseline to Week 4	25.7 Micrograms per deciliter (μg/mL) Standard Deviation 21.95	22.0 Micrograms per deciliter (μg/mL) Standard Deviation 32.18	18.7 Micrograms per deciliter (μg/mL) Standard Deviation 22.39
Change From Baseline in Total Iron-Binding Capacity (TIBC) Change from Baseline to Week 8	23.4 Micrograms per deciliter (μg/mL) Standard Deviation 28.13	30.3 Micrograms per deciliter (μg/mL) Standard Deviation 28.30	22.0 Micrograms per deciliter (μg/mL) Standard Deviation 25.37
Change From Baseline in Total Iron-Binding Capacity (TIBC) Change from Baseline to Week 12	30.6 Micrograms per deciliter (μg/mL) Standard Deviation 30.05	34.8 Micrograms per deciliter (μg/mL) Standard Deviation 28.69	23.9 Micrograms per deciliter (μg/mL) Standard Deviation 19.62
Change From Baseline in Total Iron-Binding Capacity (TIBC) Change from Baseline to Week 16	27.7 Micrograms per deciliter (μg/mL) Standard Deviation 35.27	24.9 Micrograms per deciliter (μg/mL) Standard Deviation 29.10	25.7 Micrograms per deciliter (μg/mL) Standard Deviation 21.78

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline TSAT was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=30 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Transferrin Saturation (TSAT) Baseline	34.6 Percent change Standard Deviation 11.63	33.7 Percent change Standard Deviation 11.14	37.5 Percent change Standard Deviation 13.27
Change From Baseline in Transferrin Saturation (TSAT) Change from Baseline to Week 4	5.4 Percent change Standard Deviation 15.49	2.1 Percent change Standard Deviation 16.97	3.6 Percent change Standard Deviation 15.84
Change From Baseline in Transferrin Saturation (TSAT) Change from Baseline to Week 8	2.9 Percent change Standard Deviation 15.92	1.2 Percent change Standard Deviation 17.31	3.3 Percent change Standard Deviation 14.87
Change From Baseline in Transferrin Saturation (TSAT) Change from Baseline to Week 12	9.1 Percent change Standard Deviation 19.71	1.3 Percent change Standard Deviation 17.18	3.7 Percent change Standard Deviation 14.08
Change From Baseline in Transferrin Saturation (TSAT) Change from Baseline to Week 16	2.5 Percent change Standard Deviation 14.86	1.7 Percent change Standard Deviation 17.44	2.5 Percent change Standard Deviation 13.75

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, and Week 16

Population: MITT Population

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron was defined as the last observation before the first dose of study medication.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Change From Baseline in Iron Baseline	70.6 μg/dL Standard Deviation 26.25	66.6 μg/dL Standard Deviation 23.74	75.4 μg/dL Standard Deviation 32.31
Change From Baseline in Iron Change from Baseline to Week 4	20.7 μg/dL Standard Deviation 32.47	18.5 μg/dL Standard Deviation 40.91	13.3 μg/dL Standard Deviation 30.06
Change From Baseline in Iron Change from Baseline to Week 8	14.3 μg/dL Standard Deviation 33.38	11.6 μg/dL Standard Deviation 39.10	15.0 μg/dL Standard Deviation 30.22
Change From Baseline in Iron Change from Baseline to Week 12	31.7 μg/dL Standard Deviation 46.73	10.8 μg/dL Standard Deviation 31.44	15.5 μg/dL Standard Deviation 28.01
Change From Baseline in Iron Change from Baseline to Week 16	14.0 μg/dL Standard Deviation 34.43	10.3 μg/dL Standard Deviation 37.16	14.0 μg/dL Standard Deviation 28.62

SECONDARY outcome

Timeframe: Up to Week 16

Population: Intent-to-treat (ITT) Population: All participants who were assigned to study medication and received at least 1 dose of study medication.

ESA rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy	4 Participants	6 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Week 16

Population: ITT Population

Blood transfusion rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Number of Participants Who Received Blood Transfusion Rescue Therapy	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dialysis and post-dialysis on Week 2 and Week 16

Population: ITT Population. Participants with available data were included in the analysis.

Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=27 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=30 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=27 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Mean Plasma Concentrations of Vadadustat Week 2 pre-dialysis	12.89 μg/mL Standard Deviation 13.876	17.27 μg/mL Standard Deviation 12.741	5.329 μg/mL Standard Deviation 5.0281
Mean Plasma Concentrations of Vadadustat Week 2 post-dialysis	13.72 μg/mL Standard Deviation 13.728	18.69 μg/mL Standard Deviation 15.601	5.287 μg/mL Standard Deviation 5.2117
Mean Plasma Concentrations of Vadadustat Week 16 pre-dialysis	11.41 μg/mL Standard Deviation 8.7716	15.98 μg/mL Standard Deviation 12.059	4.813 μg/mL Standard Deviation 3.6094
Mean Plasma Concentrations of Vadadustat Week 16 post-dialysis	13.85 μg/mL Standard Deviation 11.921	17.38 μg/mL Standard Deviation 12.516	3.998 μg/mL Standard Deviation 2.9709

SECONDARY outcome

Timeframe: Pre-dialysis and post-dialysis on Week 2 and Week 16

Population: ITT Population. Participants with available data were included in the analysis.

Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=27 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=30 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=28 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite Week 2 pre-dialysis	16.66 μg/mL Standard Deviation 13.508	26.36 μg/mL Standard Deviation 21.111	6.295 μg/mL Standard Deviation 4.8326
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite Week 2 post-dialysis	8.725 μg/mL Standard Deviation 7.6786	13.26 μg/mL Standard Deviation 13.154	3.101 μg/mL Standard Deviation 2.2190
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite Week 16 pre-dialysis	15.74 μg/mL Standard Deviation 14.356	17.19 μg/mL Standard Deviation 13.266	7.843 μg/mL Standard Deviation 8.0807
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite Week 16 post-dialysis	7.833 μg/mL Standard Deviation 5.5438	8.408 μg/mL Standard Deviation 6.4361	2.998 μg/mL Standard Deviation 2.5811

SECONDARY outcome

Timeframe: Pre-dialysis and post-dialysis on Week 2 and Week 16

Population: ITT Population. Participants with available data were included in the analysis.

Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=9 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=13 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=1 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite Week 2 pre-dialysis	0.0136 μg/mL Standard Deviation 0.00611	0.0224 μg/mL Standard Deviation 0.01889	0.0800 μg/mL Standard Deviation NA Dispersion data is not available for a single participant
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite Week 2 post-dialysis	0.0142 μg/mL Standard Deviation 0.01016	0.0095 μg/mL Standard Deviation 0.00246	—
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite Week 16 pre-dialysis	0.0129 μg/mL Standard Deviation 0.01083	0.0210 μg/mL Standard Deviation 0.00700	—
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite Week 16 post-dialysis	0.0100 μg/mL Standard Deviation 0.00603	0.0087 μg/mL Standard Deviation 0.00351	—

SECONDARY outcome

Timeframe: Up to Week 20

Population: ITT Population

An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. A TEAE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. A SAE included AEs that met one or more of the following criteria/outcomes: death, lifethreatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	26 Participants	26 Participants	26 Participants
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	2 Participants	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to Week 20

Population: ITT Population

Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 20

Population: ITT Population

Parameters assessed for laboratory values included hematology, serum chemistry, urinalysis, iron indices, C-reactive protein, lipid profile, biomarkers, and pregnancy tests. The investigator was responsible for reviewing laboratory results for clinically significant changes.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 20

Population: ITT Population

A standard 12-lead ECG was performed following dosing in a supine position for approximately 5 minutes. ECGs were taken prior to vital sign assessments, circulatory access cannulation, and blood draws when possible. Clinical significance was determined by the investigator.

Outcome measures

Outcome measures
Measure	Vadadustat 300 mg Once Daily (QD) n=30 Participants Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 Participants Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 Participants Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 8, and Week 16

Intravenous iron was administered throughout the study to maintain ferritin levels in the range of ≥100 ng/mL to ≤1200 ng/mL.

Outcome measures

Outcome data not reported

Adverse Events

Vadadustat 300 mg Once Daily (QD)

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Vadadustat 450 mg QD

Serious events: 9 serious events

Other events: 19 other events

Deaths: 0 deaths

Vadadustat 450 mg 3 Times Per Week (TIW)

Serious events: 8 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

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

Measure	Vadadustat 300 mg Once Daily (QD) n=30 participants at risk Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg QD n=33 participants at risk Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.	Vadadustat 450 mg 3 Times Per Week (TIW) n=31 participants at risk Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed.
Cardiac disorders Acute myocardial infarction	3.3% 1/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Cardiac disorders Bradycardia	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Cardiac disorders Cardiac failure congestive	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Cardiac disorders Palpitations	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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 Pneumonia	3.3% 1/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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 Arteriovenous fistula site infection	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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 Abscess limb	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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 Arteriovenous graft site infection	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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 Arthritis bacterial	3.3% 1/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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 Vestibular neuronitis	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	3.3% 1/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Injury, poisoning and procedural complications Delayed recovery from anaesthesia	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.0% 1/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Metabolism and nutrition disorders Fluid overload	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	3.2% 1/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.3% 1/30 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/33 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.	0.00% 0/31 • Up to Week 20 (from the time of the first dose of study medication to last dose + 4 weeks of follow-up) 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.