Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)

• Sponsor: Akebia Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03054337
• Collaborator: (none)
• Enrollment: 51
• Locations: 18
• Arms: 4
• Actual Duration (Months): 10.9
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a Phase 2, randomized, double-blind, placebo-controlled, dose-finding study to assess the efficacy, safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of orally administered vadadustat in Japanese participants with anemia secondary to Non-dialysis Dependent Chronic Kidney Disease (NDD-CKD).

Condition or Disease	Intervention/Treatment	Phase
Anemia; Non-dialysis Dependent Chronic Kidney Disease	Drug: Vadadustat; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2, Randomized, Double-Blind, Placebo Controlled, Dose-Finding Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Vadadustat in Japanese Subjects With Anemia Secondary to Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)
• Actual Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Jul 4, 2017
• Actual Study Completion Date: Aug 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vadadustat, Dose 1 Daily oral dose	Drug: Vadadustat; Other Names: AKB-6548
Experimental: Vadadustat, Dose 2 Daily oral dose	Drug: Vadadustat; Other Names: AKB-6548
Experimental: Vadadustat, Dose 3 Daily oral dose	Drug: Vadadustat; Other Names: AKB-6548
Placebo Comparator: Placebo Daily oral dose	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period [Pre-treatment; Week 6]

   The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 6 value minus the Pre-treatment value.

Secondary Outcome Measures

1. Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 [from Baseline up to Week 16]

   Time for this analysis was measured from Day 1 (Baseline) through the point in time during either the Primary Efficacy Period or the Dose Adjustment and Maintenance Period when a participant's Hb level achieved the target range of 10.0 to 12.0 g/dL.

2. Mean Hb Levels at the End of the Primary Efficacy Period [up to Week 6]

   Data are reported as mean of the actual Week 6 values.

3. Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period [up to Week 16]

   Data are reported as mean of the actual Week 16 values.

4. Number of Participants Who Achieved the Target Hb Level of 10.0 to 12.0 g/dL at the End of the Dose Adjustment and Maintenance Period [up to Week 16]

5. Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period [Pre-treatment; Week 16]

   The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value.

6. Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period [Baseline; Week 6]

   Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

7. Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline; Week 16]

   Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

8. Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period [Baseline; Week 6]

   Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

9. Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline; Week 16]

   Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

10. Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period [Baseline; Week 6]

    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

11. Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline; Week 16]

    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

12. Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period [Baseline; Week 6]

    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

13. Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline; Week 16]

    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

14. Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period [Baseline; Week 6]

    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

15. Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline; Week 16]

    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

16. Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period [Baseline; Week 6]

    ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is <9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion. Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.

17. Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline; Week 16]

    ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is <9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion. Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.

18. Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period [Baseline; Week 6]

    Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.

19. Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline; Week 16]

    Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.

20. Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period [Baseline to Week 16]

    Increases in dose were not allowed during the 6-week Primary Efficacy Period.

21. Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 [Baseline to Week 6]

    Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.

22. Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 [Baseline to Week 16]

    Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.

23. Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 [Week 4, pre-dose]

    Blood samples were collected for analysis.

24. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period [up to Week 6]

    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. An AE 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. An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/ incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.

25. Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period [up to Week 16]

    An AE was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. An AE 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. An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female Japanese participants ≥20 years of age

• Diagnosis of chronic kidney disease (CKD) based on an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m^2)

• Hemoglobin (Hb) ≤10.5 grams per deciliter (g/dL)

• Not currently being treated with dialysis and not expected to start dialysis within 3 months of screening

Exclusion Criteria:

• Anemia due to a cause other than CKD or presence of active bleeding or recent blood loss

• Sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia

• Red blood cell transfusion within 4 weeks prior to or during screening

• Intravenous iron within 4 weeks prior to or during screening

• Any use of erythropoiesis-stimulating agents within 6 weeks prior to or during screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Aichi		Japan
2		Chiba		Japan
3		Ehime		Japan
4		Gunma		Japan
5		Hiroshima		Japan
6		Hokkaido		Japan
7		Hyogo		Japan
8		Ibaraki		Japan
9		Kanagawa		Japan
10		Nagano		Japan
11		Nara		Japan
12		Niigata		Japan
13		Oita		Japan
14		Okayama		Japan
15		Okinawa		Japan
16		Osaka		Japan
17		Shiga		Japan
18		Tokushima		Japan

Sponsors and Collaborators

• Akebia Therapeutics

Investigators

• Study Director: Akebia Therapeutics, Sponsor GmbH

Study Documents (Full-Text)

• Study Protocol - Dec 15, 2016
• Statistical Analysis Plan - Jul 24, 2017

More Information

Publications

None provided.

• Responsible Party: Akebia Therapeutics
• ClinicalTrials.gov Identifier: NCT03054337
• Other Study ID Numbers: AKB-6548-CI-0021
• First Posted: Feb 15, 2017
• Last Update Posted: Apr 8, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Akebia Therapeutics: Anemia; kidney; non-dialysis dependent chronic kidney disease; CKD; NDD-CKD; renal; vadadustat; AKB-6548; hypoxia-inducible factor; hypoxia-inducible factor (HIF); HIF; prolyl-hydroxylase inhibitor (PHI); PHI; Japan; Japanese; Akebia (AKB)
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia

Study Results

Participant Flow

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 milligrams (mg), administered as 1 tablet once daily (QD), for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target hemoglobin (Hb) of 10.0 to 12.0 grams/deciliter (g/dL) based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Period Title: Primary Efficacy Period (6 Weeks)
STARTED	12	12	13	5	4	5
COMPLETED	12	12	13	5	4	5
NOT COMPLETED	0	0	0	0	0	0
Period Title: Primary Efficacy Period (6 Weeks)
STARTED	12	12	13	5	4	5
COMPLETED	11	10	12	5	4	4
NOT COMPLETED	1	2	1	0	0	1

Baseline Characteristics

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg	Total
Arm/Group Description	Participants were randomized to receive vadadustat 150 milligrams (mg), administered as 1 tablet once daily (QD), for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target hemoglobin (Hb) of 10.0 to 12.0 grams/deciliter (g/dL) based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Total of all reporting groups
Overall Participants	12	12	13	5	4	5	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.9 (10.33)	65.8 (11.53)	71.5 (12.84)	73.4 (3.05)	68.0 (21.21)	72.2 (8.64)	70.2 (11.55)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	5 41.7%	8 61.5%	1 20%	1 25%	2 40%	22 43.1%
Male	7 58.3%	7 58.3%	5 38.5%	4 80%	3 75%	3 60%	29 56.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Hemoglobin Levels (grams per deciliter (g/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams per deciliter (g/dL)]	9.958 (0.8051)	9.492 (0.8867)	9.500 (0.8446)	10.280 (0.9365)	9.625 (0.6551)	9.680 (0.8198)	9.710 (0.8410)

Outcome Measures

1. Primary Outcome

Title	Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period
Description	The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 6 value minus the Pre-treatment value.
Time Frame	Pre-treatment; Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population (mITT): all randomized participants who received at least 1 dose of study medication, had a pre-treatment Hb average, and at least one post-Baseline Hb measurement. The mITT Population was based on the treatment to which participants were randomized.

Arm/Group Title	Vadadustat 150	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 milligrams (mg), administered as 1 tablet once daily (QD), for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Least Squares Mean (Standard Error) [grams per deciliter (g/dL)]	0.43 (0.224)	1.13 (0.223)	1.62 (0.215)	-0.47 (0.206)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0045
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) model included treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.29 to 1.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.301
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model included treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.98 to 2.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.306
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model included treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	2.09
	Confidence Interval	(2-Sided) 95%; 1.49 to 2.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.300
	Estimation Comments

2. Secondary Outcome

Title	Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16
Description	Time for this analysis was measured from Day 1 (Baseline) through the point in time during either the Primary Efficacy Period or the Dose Adjustment and Maintenance Period when a participant's Hb level achieved the target range of 10.0 to 12.0 g/dL.
Time Frame	from Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with Hb < 10.0 g/dL at the Baseline visit were included in the analysis.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target hemoglobin (Hb) of 10.0 to 12.0 grams/deciliter (g/dL) based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets OD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target hemoglobin of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	6	7	8	2	3	4
Mean (Standard Deviation) [days]	56.8 (43.31)	39.0 (38.52)	25.6 (16.47)	79.0 (11.31)	71.0 (14.00)	54.5 (33.67)

3. Secondary Outcome

Title	Mean Hb Levels at the End of the Primary Efficacy Period
Description	Data are reported as mean of the actual Week 6 values.
Time Frame	up to Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Mean (Standard Deviation) [g/dL]	10.392 (0.7280)	10.675 (1.2693)	11.162 (1.1169)	9.421 (0.9242)

4. Secondary Outcome

Title	Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period
Description	Data are reported as mean of the actual Week 16 values.
Time Frame	up to Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
Mean (Standard Deviation) [g/dL]	10.973 (0.5711)	11.230 (0.7514)	11.342 (0.6473)	10.860 (0.5857)	11.425 (0.9179)	11.950 (0.6608)

5. Secondary Outcome

Title	Number of Participants Who Achieved the Target Hb Level of 10.0 to 12.0 g/dL at the End of the Dose Adjustment and Maintenance Period
Time Frame	up to Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
Count of Participants [Participants]	11 91.7%	8 66.7%	11 84.6%	5 100%	3 75%	2 40%

6. Secondary Outcome

Title	Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
Description	The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value.
Time Frame	Pre-treatment; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
Mean (Standard Deviation) [g/dL]	0.982 (0.3676)	1.610 (1.1692)	1.779 (0.8117)	0.790 (0.3070)	1.538 (0.5250)	2.075 (0.2784)

7. Secondary Outcome

Title	Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
RBC Count	0.17 (0.075)	0.34 (0.075)	0.48 (0.073)	-0.17 (0.070)
Absolute Reticulocyte Count	0.01 (0.004)	0.01 (0.003)	0.01 (0.003)	0.01 (0.003)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	RBC Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; 0.13 to 0.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.103
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	RBC Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; 0.30 to 0.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.103
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	RBC Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.102
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	Absolute Reticulocyte Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7804
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.005
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	Absolute Reticulocyte Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0986
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.005
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	Absolute Reticulocyte Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1661
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.005
	Estimation Comments

8. Secondary Outcome

Title	Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
RBC Count	0.305 (0.1870)	0.476 (0.4406)	0.593 (0.3186)	0.186 (0.2165)	0.438 (0.2175)	0.608 (0.1771)
Absolute Reticulocyte Count	0.003078 (0.0094008)	0.008001 (0.0156884)	0.000196 (0.0085029)	0.010716 (0.0279909)	0.009703 (0.0103348)	0.000595 (0.0171563)

9. Secondary Outcome

Title	Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Hematocrit	2.13 (0.696)	4.13 (0.696)	6.07 (0.667)	-1.17 (0.643)
Reticulocytes	0.16 (0.111)	0.28 (0.111)	0.19 (0.107)	0.25 (0.103)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	Hematocrit
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	3.30
	Confidence Interval	(2-Sided) 95%; 1.40 to 5.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.942
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	Hematocrit
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	5.30
	Confidence Interval	(2-Sided) 95%; 3.38 to 7.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.953
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	Hematocrit
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	7.24
	Confidence Interval	(2-Sided) 95%; 5.37 to 9.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.930
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	Reticulocytes
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5889
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.152
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	Reticulocytes
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8074
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.151
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	Reticulocytes
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6952
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model will include treatment assignment (3 dosed groups; 1 placebo group) and pre-treatment Hb value as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.148
	Estimation Comments

10. Secondary Outcome

Title	Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
Hematocrit	3.28 (1.947)	5.17 (4.991)	5.39 (2.844)	2.32 (1.827)	5.80 (1.566)	6.05 (1.997)
Reticulocytes	-0.02 (0.232)	0.07 (0.442)	-0.18 (0.279)	0.28 (0.893)	0.15 (0.238)	-0.18 (0.377)

11. Secondary Outcome

Title	Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 6

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Iron	-1.8 (19.58)	-2.4 (20.75)	4.4 (30.82)	-7.4 (19.92)
TIBC	44.9 (32.9)	75.2 (35.60)	93.8 (44.74)	7.6 (23.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	Iron
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3702
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	Iron
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5524
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	Iron
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1589
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	TIBC
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0092
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	TIBC
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	TIBC
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

12. Secondary Outcome

Title	Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
Iron	11.7 (38.25)	3.5 (31.17)	11.5 (28.56)	-1.4 (21.82)	5.5 (24.66)	5.8 (25.59)
TIBC	51.8 (48.41)	43.4 (42.77)	42.8 (28.28)	47.6 (21.71)	73.5 (39.95)	44.5 (43.19)

13. Secondary Outcome

Title	Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Mean (Standard Deviation) [percentage]	-4.96 (7.343)	-7.31 (8.380)	-6.78 (10.609)	-4.72 (8.931)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9092
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1484
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1313
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

14. Secondary Outcome

Title	Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
Mean (Standard Deviation) [percentage]	-1.47 (10.365)	-2.68 (13.201)	-0.19 (9.857)	-7.00 (12.247)	-5.03 (11.342)	-2.68 (10.608)

15. Secondary Outcome

Title	Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Ferritin	-38.48 (34.227)	-69.36 (49.965)	-101.54 (57.697)	-11.44 (31.408)
Hepcidin	-24.622 (20.0165)	-40.819 (27.2486)	-37.964 (21.0819)	-3.824 (18.4986)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	Ferritin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1080
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	Ferritin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	Ferritin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments	Hepcidin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0672
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg, Placebo
	Comments	Hepcidin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg, Placebo
	Comments	Hepcidin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

16. Secondary Outcome

Title	Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	11	10	12	5	4	4
Ferritin	-79.45 (39.655)	-62.35 (36.808)	-59.68 (59.843)	-69.26 (46.519)	-146.63 (34.261)	-59.43 (13.618)
Hepcidin	-29.522 (22.7101)	-23.061 (53.0161)	-2.502 (21.2660)	-9.464 (19.1361)	-38.920 (23.4788)	-9.745 (9.2100)

17. Secondary Outcome

Title	Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period
Description	ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is <9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion. Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.
Time Frame	Baseline; Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is <9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion. Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.
Time Frame	Baseline; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	12	12	13	5	4	5
Count of Participants [Participants]	0 0%	2 16.7%	1 7.7%	0 0%	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period
Description	Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Time Frame	Baseline; Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participant with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

20. Secondary Outcome

Title	Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Time Frame	Baseline; Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	12	12	13	5	4	5
Count of Participants [Participants]	0 0%	1 8.3%	1 7.7%	0 0%	0 0%	1 20%

21. Secondary Outcome

Title	Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period
Description	Increases in dose were not allowed during the 6-week Primary Efficacy Period.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	12	12	13	5	4	5
0 dose adjustments	3 25%	1 8.3%	2 15.4%	0 0%	0 0%	1 20%
1 dose adjustment	5 41.7%	7 58.3%	1 7.7%	3 60%	1 25%	1 20%
2 dose adjustments	3 25%	4 33.3%	3 23.1%	1 20%	1 25%	2 40%
3 or more dose adjustments	1 8.3%	0 0%	7 53.8%	1 20%	2 50%	1 20%

22. Secondary Outcome

Title	Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6
Description	Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
Iron sufficiency maintained	7 58.3%	4 33.3%	4 30.8%	9 180%
Iron sufficiency not maintained	5 41.7%	8 66.7%	9 69.2%	5 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0895
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 300 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 600 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3845
	Comments
	Method	Fisher Exact
	Comments

23. Secondary Outcome

Title	Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16
Description	Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	12	12	13	5	4	5
Iron sufficiency maintained	6 50%	2 16.7%	4 30.8%	1 20%	1 25%	0 0%
Iron sufficiency not maintained	6 50%	10 83.3%	9 69.2%	4 80%	3 75%	5 100%

24. Secondary Outcome

Title	Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4
Description	Blood samples were collected for analysis.
Time Frame	Week 4, pre-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Population: all participants in the Safety Population (all enrolled participants who received at least 1 dose of study medication) who had a pre-dose PK sample at Week 4.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	0
Vadadustat	5530.9 (4168.86)	12955.8 (9771.65)	19291.5 (9325.30)
O-glucuronide	3914.7 (5772.39)	12358.6 (7586.73)	16586.2 (12363.44)
Acyl-glucuronide	0.00 (0.000)	1.95 (6.755)	8.99 (16.430)

25. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period
Description	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. An AE 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. An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/ incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.
Time Frame	up to Week 6

Outcome Measure Data

Analysis Population Description

Safety Population: all enrolled participants who received at least 1 dose of study medication. The Safety Population was based on the actual treatment that participants received.

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.	Participants were randomized to receive matching placebo for 6 weeks.
Measure Participants	12	12	13	14
TEAEs	4 33.3%	7 58.3%	7 53.8%	5 100%
Treatment-emergent SAEs	0 0%	0 0%	0 0%	0 0%

26. Secondary Outcome

Title	Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period
Description	An AE was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. An AE 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. An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.
Time Frame	up to Week 16

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Vadadustat 150 mg	Vadadustat 300 mg	Vadadustat 600 mg	Placebo to Vadadustat 150 mg	Placebo to Vadadustat 300 mg	Placebo to Vadadustat 600 mg
Arm/Group Description	Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.	Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
Measure Participants	12	12	13	5	4	5
TEAEs	9 75%	10 83.3%	6 46.2%	3 60%	3 75%	3 60%
Treatment-emergent SAEs	0 0%	5 41.7%	2 15.4%	1 20%	1 25%	2 40%

Adverse Events

Time Frame	up to Week 18
Arm/Group Title	Primary Efficacy Period: 150 mg Vadadustat		Primary Efficacy Period: 300 mg Vadadustat		Primary Efficacy Period: 600 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 150 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 300 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 600 mg Vadadustat		Dose Adjustment and Maintenance: 150 mg Vadadustat		Dose Adjustment and Maintenance: 300 mg Vadadustat		Dose Adjustment and Maintenance: 600 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 150 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 300 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 600 mg Vadadustat
Arm/Group Description	Participants were randomized to receive vadadustat 150 milligrams (mg), administered as 1 tablet once daily (QD), for 6 weeks.		Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks.		Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks.		Participants were randomized to receive matching placebo for 6 weeks.		Participants were randomized to receive matching placebo for 6 weeks.		Participants were randomized to receive matching placebo for 6 weeks.		Participants were randomized to receive vadadustat 150 mg, administered as 1 tablet QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target hemoglobin (Hb) of 10.0 to 12.0 grams per deciliter (g/dL) based on dose adjustment guidelines.		Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.		Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.		Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.		Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.		Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines.
All Cause Mortality
	Primary Efficacy Period: 150 mg Vadadustat		Primary Efficacy Period: 300 mg Vadadustat		Primary Efficacy Period: 600 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 150 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 300 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 600 mg Vadadustat		Dose Adjustment and Maintenance: 150 mg Vadadustat		Dose Adjustment and Maintenance: 300 mg Vadadustat		Dose Adjustment and Maintenance: 600 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 150 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 300 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 600 mg Vadadustat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Serious Adverse Events
	Primary Efficacy Period: 150 mg Vadadustat		Primary Efficacy Period: 300 mg Vadadustat		Primary Efficacy Period: 600 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 150 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 300 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 600 mg Vadadustat		Dose Adjustment and Maintenance: 150 mg Vadadustat		Dose Adjustment and Maintenance: 300 mg Vadadustat		Dose Adjustment and Maintenance: 600 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 150 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 300 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 600 mg Vadadustat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		5/12 (41.7%)		2/13 (15.4%)		1/5 (20%)		1/4 (25%)		2/5 (40%)
Gastrointestinal disorders
Duodenal ulcer hemorrhage	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)
Hepatobiliary disorders
Hepatic function abnormal	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Infections and infestations
Influenza	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)
Lung infection	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Injury, poisoning and procedural complications
Spinal compression fracture	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		1/5 (20%)		0/4 (0%)		0/5 (0%)
Renal and urinary disorders
Acute kidney injury	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
End-stage renal disease	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Renal impairment	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)
Interstitial lung disease	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Surgical and medical procedures
Arteriovenous shunt procedure	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		3/12 (25%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Primary Efficacy Period: 150 mg Vadadustat		Primary Efficacy Period: 300 mg Vadadustat		Primary Efficacy Period: 600 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 150 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 300 mg Vadadustat		Primary Efficacy Period: Placebo Matched to 600 mg Vadadustat		Dose Adjustment and Maintenance: 150 mg Vadadustat		Dose Adjustment and Maintenance: 300 mg Vadadustat		Dose Adjustment and Maintenance: 600 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 150 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 300 mg Vadadustat		Dose Adjustment and Maintenance: Placebo to 600 mg Vadadustat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/12 (33.3%)		7/12 (58.3%)		7/13 (53.8%)		0/5 (0%)		2/4 (50%)		3/5 (60%)		9/12 (75%)		10/12 (83.3%)		6/13 (46.2%)		2/5 (40%)		2/4 (50%)		2/5 (40%)
Endocrine disorders
Hypothyroidism	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Parathyroid gland enlargement	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Eye disorders
Conjunctival haemorrhage	0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Gastrointestinal disorders
Constipation	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		2/12 (16.7%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)
Diarrhoea	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		1/13 (7.7%)		1/5 (20%)		0/4 (0%)		0/5 (0%)
Nausea	0/12 (0%)		2/12 (16.7%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Abdominal distension	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Dental caries	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)
Stomatitis	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)
Periodontal disease	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Vomiting	1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Enterocolitis	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Gastrooesophageal reflux disease	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Tooth loss	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Abdominal pain	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
General disorders
Oedema due to renal disease	1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)
Oedema peripheral	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Infections and infestations
Viral upper respiratory tract infection	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)		1/12 (8.3%)		1/12 (8.3%)		1/13 (7.7%)		1/5 (20%)		0/4 (0%)		0/5 (0%)
Influenza	1/12 (8.3%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Cystitis	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)
Herpes simplex	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)
Angular cheilitis	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Urinary tract infection	0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Herpes zoster	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Otitis externa	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Paronychia	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Upper respiratory tract infection bacterial	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Upper respiratory tract infection	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Injury, poisoning and procedural complications
Contusion	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)		2/12 (16.7%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Fall	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Face injury	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Injury	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Laceration	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Spinal compression fracture	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Sternal fracture	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Tooth fracture	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Wound	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Investigations
Aspartate aminotransferase increased	0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Dehydration	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Metabolic acidosis	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Hyperphosphataemia	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Hypoglycaemia	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Muscle spasms	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Pain in extremity	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Nervous system disorders
Dizziness	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)
Loss of consciousness	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)
Headache	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Psychiatric disorders
Delirium	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Renal and urinary disorders
Renal impairment	0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Chronic kidney disease	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Diabetic nephropathy	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Hypertensive nephropathy	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Pollakiuria	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Reproductive system and breast disorders
Uterine prolapse	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Benign prostatic hyperplasia	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		1/13 (7.7%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Pulmonary hypertension	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Reflux laryngitis	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Skin and subcutaneous tissue disorders
Eczema	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Eczema asteatotic	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		1/12 (8.3%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Vascular disorders
Hypertension	0/12 (0%)		3/12 (25%)		2/13 (15.4%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)
Orthostatic hypotension	1/12 (8.3%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/12 (0%)		0/12 (0%)		0/13 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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