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

• Sponsor: Akebia Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03054350
• Collaborator: (none)
• Enrollment: 60
• Locations: 18
• Arms: 4
• Actual Duration (Months): 13.8
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

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 Dialysis-dependent Chronic Kidney Disease (DD-CKD).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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 Dialysis-Dependent Chronic Kidney Disease (DD-CKD)
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Oct 24, 2017
• Actual Study Completion Date: Jan 24, 2018

Arms and Interventions

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

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 average value for Hb was defined as the average of 3 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]

   A pre-treatment average value for Hb was defined as the average of 3 values obtained prior to dosing, i.e., the 2 qualifying screening values 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 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.

17. Number of Participants Who Required Rescue With 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.

18. 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.

19. 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.

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

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

21. 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.

22. 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.

23. 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

• Receiving chronic maintenance hemodialysis for end-stage kidney disease

• Hemoglobin (Hb) <10.0 grams per deciliter (g/dL)

Exclusion Criteria:

• Anemia due to a cause other than chronic kidney disease (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

• Anticipated to recover adequate kidney function to no longer require hemodialysis during study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Aichi		Japan
2		Ehime		Japan
3		Fukui		Japan
4		Hiroshima		Japan
5		Hokkaido		Japan
6		Hyogo		Japan
7		Ibaraki		Japan
8		Kagoshima		Japan
9		Kochi		Japan
10		Miyagi		Japan
11		Nagano		Japan
12		Nagasaki		Japan
13		Niigata		Japan
14		Oita		Japan
15		Okinawa		Japan
16		Osaka		Japan
17		Saitama		Japan
18		Shizuoka		Japan

Sponsors and Collaborators

• Akebia Therapeutics

Investigators

• Study Director: Akebia Therapeutics, Sponsor GmbH

Study Documents (Full-Text)

• Study Protocol - Feb 3, 2017
• Statistical Analysis Plan - Aug 25, 2017

More Information

Publications

None provided.

• Responsible Party: Akebia Therapeutics
• ClinicalTrials.gov Identifier: NCT03054350
• Other Study ID Numbers: AKB-6548-CI-0022
• 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
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Akebia Therapeutics: Anemia; kidney; dialysis dependent chronic kidney disease; CKD; DD; renal; vadadustat; AKB-6548; hypoxia-inducible factor; Akebia (AKB); hypoxia-inducible factor (HIF); HIF; prolyl-hydroxylase inhibitor (PHI); PHI; Japan; Japanese
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia

Study Results

Participant Flow

Pre-assignment Detail	Participants who had not recently received erythropoiesis-stimulating agent (ESA) therapy participated in 2 screening visits (SVs). Participants who had recently received ESA therapy and otherwise met the eligibility criteria were required to washout from ESA therapy prior to evaluation of screening hemoglobin levels and participate in 3 SVs.

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	15	15	15	5	5	5
COMPLETED	11	13	13	3	1	2
NOT COMPLETED	4	2	2	2	4	3
Period Title: Primary Efficacy Period (6 Weeks)
STARTED	11	13	13	3	1	2
COMPLETED	10	13	12	2	1	2
NOT COMPLETED	1	0	1	1	0	0

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	15	15	15	5	5	5	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.5 (11.01)	64.3 (8.02)	65.1 (9.05)	60.8 (12.85)	61.0 (15.60)	70.8 (8.23)	63.8 (10.16)
Sex: Female, Male (Count of Participants)
Female	5 33.3%	2 13.3%	5 33.3%	2 40%	3 60%	2 40%	19 31.7%
Male	10 66.7%	13 86.7%	10 66.7%	3 60%	2 40%	3 60%	41 68.3%
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)]	8.996 (0.5229)	8.793 (0.5254)	9.317 (0.6222)	8.827 (0.6405)	8.950 (0.7331)	9.133 (0.6737)	9.015 (0.5935)

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 average value for Hb was defined as the average of 3 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 mg	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	15	15	14	14
Least Squares Mean (Standard Error) [grams per deciliter (g/dL)]	-0.28 (0.218)	0.08 (0.222)	0.41 (0.233)	-1.48 (0.226)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) model includes 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	1.19
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.314
	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 includes 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	1.56
	Confidence Interval	(2-Sided) 95%; 0.93 to 2.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.315
	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 includes 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	1.89
	Confidence Interval	(2-Sided) 95%; 1.23 to 2.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.326
	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 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	8	12	11	0	2	1
Mean (Standard Deviation) [days]	69.3 (25.31)	79.2 (24.94)	54.6 (27.90)	57.0 (19.80)	85.0 (NA)

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 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	11	13	13	6
Mean (Standard Deviation) [g/dL]	9.064 (1.0652)	9.062 (0.8412)	9.969 (0.7296)	7.817 (1.4662)

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 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 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 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 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 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	10	13	12	2	1	2
Mean (Standard Deviation) [g/dL]	10.460 (0.7501)	11.285 (1.7841)	11.100 (1.1402)	8.600 (0.9899)	13.200 (NA)	12.100 (1.5556)

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	10	13	12	2	1	2
Count of Participants [Participants]	7 46.7%	11 73.3%	7 46.7%	0 0%	0 0%	1 20%

6. Secondary Outcome

Title	Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
Description	A pre-treatment average value for Hb was defined as the average of 3 values obtained prior to dosing, i.e., the 2 qualifying screening values 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	10	13	12	2	1	2
Mean (Standard Deviation) [g/dL]	1.397 (0.5755)	2.444 (1.7807)	1.644 (1.4973)	-0.233 (0.1414)	3.800 (NA)	3.000 (0.2828)

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	11	13	13	6
RBC Count	-0.01 (0.073)	0.08 (0.069)	0.20 (0.069)	-0.30 (0.099)
Absolute Reticulocyte Count	0.02 (0.005)	0.02 (0.004)	0.03 (0.004)	0.01 (0.006)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments	RBC Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0232
	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	0.29
	Confidence Interval	(2-Sided) 95%; 0.04 to 0.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.122
	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	0.0033
	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	0.38
	Confidence Interval	(2-Sided) 95%; 0.13 to 0.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.121
	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	0.0002
	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	0.50
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.120
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments	Absolute Reticulocyte Count
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3289
	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) 94%; -0.01 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.008
	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	0.2607
	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%; -0.01 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.007
	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	0.0252
	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	0.02
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.007
	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	10	13	12	2	1	2
RBC Count	0.454 (0.2225)	0.819 (0.5127)	0.503 (0.5056)	0.065 (0.0212)	1.160 (NA)	1.035 (0.0778)
Absolute Reticulocyte Count	0.017 (0.0169)	0.021 (0.0180)	0.016 (0.0162)	0.016 (0.0083)	0.024 (NA)	0.014 (0.0217)

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	11	13	13	6
Hematocrit	0.67 (0.770)	1.98 (0.737)	3.30 (0.737)	-2.63 (1.045)
Reticulocytes	0.64 (0.158)	0.57 (0.141)	0.71 (0.140)	0.39 (0.212)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments	Hematocrit
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0154
	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	3.31
	Confidence Interval	(2-Sided) 95%; 0.67 to 5.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.303
	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	0.0008
	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	4.61
	Confidence Interval	(2-Sided) 95%; 2.06 to 7.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.261
	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	5.93
	Confidence Interval	(2-Sided) 95%; 3.31 to 8.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.296
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments	Reticulocytes
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3572
	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	0.25
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.273
	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	0.4758
	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	0.18
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.252
	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	0.2048
	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	0.33
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.254
	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	10	13	12	2	1	2
Hematocrit	5.12 (2.105)	8.92 (5.100)	5.63 (4.921)	1.20 (0.000)	12.90 (NA)	10.70 (1.697)
Reticulocytes	0.32 (0.636)	0.33 (0.686)	0.24 (0.547)	0.55 (0.212)	0.40 (NA)	0.15 (0.636)

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. 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	11	13	13	6
Iron	-3.3 (26.60)	-1.5 (19.50)	-8.1 (21.95)	-1.5 (26.64)
TIBC	35.4 (28.72)	67.5 (25.72)	80.7 (39.04)	15.8 (8.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments	Iron
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9373
	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	0.6623
	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	0.9374
	Comments
	Method	ANCOVA
	Comments	test of treatment group difference based on ANCOVA model

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments	TIBC
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2085
	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	0.0016
	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	10	13	12	2	1	2
Iron	-18.5 (24.01)	-8.7 (24.29)	0.9 (48.22)	-9.5 (30.41)	-7.0 (NA)	15.0 (43.84)
TIBC	58.5 (44.12)	80.9 (29.42)	85.4 (39.91)	33.0 (2.83)	108.0 (NA)	78.0 (62.23)

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	11	13	13	6
Mean (Standard Deviation) [percentage]	-6.51 (11.621)	-10.14 (11.294)	-12.46 (9.544)	-2.78 (12.822)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2708
	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	0.0966
	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	0.0424
	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	10	13	12	2	1	2
Mean (Standard Deviation) [percentage]	-14.25 (12.069)	-13.79 (13.549)	-10.93 (12.627)	-12.50 (18.526)	-17.10 (NA)	-4.70 (12.021)

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	11	13	13	6
Ferritin	-51.20 (58.855)	-68.67 (54.707)	-104.49 (49.558)	12.63 (32.424)
Hepcidin	-53.465 (43.5531)	-73.587 (32.3547)	-104.301 (36.7636)	-11.802 (13.6518)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat 150 mg, Placebo
	Comments	Ferritin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0207
	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	0.0022
	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 mg, Placebo
	Comments	Hepcidin
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0062
	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	0.0002
	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	test of treatment group difference based on ANCOVA model
	Method	ANCOVA
	Comments

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	10	13	12	2	1	2
Ferritin	-105.09 (55.837)	-119.28 (84.000)	-113.52 (54.559)	-43.05 (81.954)	-150.70 (NA)	-76.95 (42.356)
Hepcidin	-73.826 (50.9042)	-99.367 (51.3174)	-106.838 (40.1472)	-95.940 (98.7262)	-122.300 (NA)	-35.140 (62.9184)

17. 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 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	15	15	14	14
Count of Participants [Participants]	0 0%	0 0%	1 6.7%	3 60%

18. Secondary Outcome

Title	Number of Participants Who Required Rescue With 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	15	15	14	5	4	5
Count of Participants [Participants]	1 6.7%	0 0%	0 0%	0 0%	0 0%	0 0%

19. 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	15	15	14	14
Count of Participants [Participants]	4 26.7%	2 13.3%	1 6.7%	8 160%

20. 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	15	15	14	5	4	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	1 20%	0 0%	0 0%

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	up to Week 16

Outcome Measure Data

Analysis Population Description

mITT 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	15	15	14	5	4	5
0 dose adjustments	5 33.3%	3 20%	9 60%	2 40%	3 60%	3 60%
1 dose adjustment	2 13.3%	2 13.3%	2 13.3%	1 20%	0 0%	0 0%
2 dose adjustments	5 33.3%	8 53.3%	3 20%	1 20%	1 20%	2 40%
3 or more dose adjustments	3 20%	2 13.3%	0 0%	1 20%	0 0%	0 0%

22. 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	13	13	0
Vadadustat	4343.54 (175.17)	7561.36 (134.77)	15083.03 (46.77)
O-glucuronide	8667.97 (73.79)	14623.89 (67.44)	36476.33 (57.18)
Acyl-glucuronide	12.019 (16.55)	12.174 (8.10)	22.765 (70.53)

23. 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	15	15	15	15
TEAEs	8 53.3%	11 73.3%	6 40%	6 120%
Treatment-emergent SAEs	0 0%	0 0%	3 20%	1 20%

24. 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	15	15	15	5	5	5
TEAEs	9 60%	9 60%	9 60%	1 20%	1 20%	2 40%
Treatment-emergent SAEs	1 6.7%	1 6.7%	1 6.7%	0 0%	0 0%	0 0%

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/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	8/15 (53.3%)		11/15 (73.3%)		6/15 (40%)		2/5 (40%)		2/5 (40%)		2/5 (40%)		9/15 (60%)		9/15 (60%)		9/15 (60%)		1/5 (20%)		1/5 (20%)		2/5 (40%)
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	0/15 (0%)		0/15 (0%)		3/15 (20%)		0/5 (0%)		1/5 (20%)		0/5 (0%)		1/15 (6.7%)		1/15 (6.7%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Cardiac disorders
Pericarditis	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Gastrointestinal disorders
Gastric ulcer haemorrhage	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Infections and infestations
Enteritis infectious	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula site complication	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Shunt stenosis	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Nervous system disorders
Cerebral haemorrhage	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Toxic encephalopathy	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Psychiatric disorders
Anxiety	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (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	8/15 (53.3%)		11/15 (73.3%)		5/15 (33.3%)		2/5 (40%)		2/5 (40%)		2/5 (40%)		9/15 (60%)		9/15 (60%)		9/15 (60%)		1/5 (20%)		1/5 (20%)		2/5 (40%)
Blood and lymphatic system disorders
Anaemia macrocytic	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Cardiac disorders
Cardiac failure chronic	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Eye disorders
Diabetic retinopathy	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Gastrointestinal disorders
Abdominal pain	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Constipation	1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Diarrhoea	0/15 (0%)		2/15 (13.3%)		2/15 (13.3%)		1/5 (20%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		1/5 (20%)		0/5 (0%)		1/5 (20%)
Faeces soft	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Nausea	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Pancreatic cyst	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Enterocolitis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Stomatitis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Vomiting	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
General disorders
Chest discomfort	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Pyrexia	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Catheter site erosion	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Vessel puncture site pruritus	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Hepatobiliary disorders
Cholelithiasis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Infections and infestations
Bronchitis	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Herpes zoster	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Nasopharyngitis	1/15 (6.7%)		5/15 (33.3%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		4/15 (26.7%)		2/15 (13.3%)		0/15 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Pneumonia	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Tracheobronchitis	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Upper respiratory tract infection	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Conjunctivitis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Gingivitis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Periodontitis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Injury, poisoning and procedural complications
Contusion	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		1/5 (20%)		0/5 (0%)		2/15 (13.3%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Excoriation	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Foreign body	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Shunt stenosis	1/15 (6.7%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Arteriovenous fistula site complication	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Thermal burn	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Vascular graft stenosis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Investigations
Blood parathyroid hormone increased	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Blood pressure increased	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Blood uric acid decreased	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Metabolism and nutrition disorders
Hypocalcaemia	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Musculoskeletal pain	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Myalgia	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Pain in extremity	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Back pain	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Muscle spasms	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Tenosynovitis	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Nervous system disorders
Headache	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		2/15 (13.3%)		0/15 (0%)		1/15 (6.7%)		1/5 (20%)		0/5 (0%)		1/5 (20%)
Diabetic neuropathy	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Post herpetic neuralgia	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Restless legs syndrome	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Psychiatric disorders
Insomnia	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)		1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Asthma	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Rhinitis allergic	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Sleep apnoea syndrome	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Upper respiratory tract inflammation	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Skin and subcutaneous tissue disorders
Neurodermatitis	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Pruritus	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Dermal cyst	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Eczema	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Ingrowing nail	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Rash pruritic	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Vascular disorders
Haemorrhage	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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