20-Week Repeat Oral Dose Study of AKB-6548 in Participant... | NCT01906489

Label	Type	Description	Intervention Names
AKB-6548	Experimental		Drug: AKB-6548
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
AKB-6548	Drug	Oral dose administered once daily for 20 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.	AKB-6548

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

Measure	Description	Time Frame
Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study	Participants who have experienced an excursion in Hgb to ≥13.0 g/dL at any time during the study were considered as "failures". Data was presented for failures.	Up to 20 Weeks
Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value

Measure	Description	Time Frame
Exploratory: Change From Baseline in Iron and Total Iron Binding Capacity (TIBC)		Baseline and up to Week 20
Exploratory: Change From Baseline in Transferrin		Baseline and up to Week 20

Name	Affiliation	Role
Chief Medical Officer	Akebia Therapeutics	Study Director

PubMed Identifier	Type	Citation	Retractions
36005278	Derived	Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
27650732	Derived	Pergola PE, Spinowitz BS, Hartman CS, Maroni BJ, Haase VH. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Kidney Int. 2016 Nov;90(5):1115-1122. doi: 10.1016/j.kint.2016.07.019. Epub 2016 Sep 17.

ID	Title	Description
FG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Achieving a Successful Hemoglobin Response

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

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

Posted

Number

Percentage of participants

Weeks 19 and 20

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants	OG000102 OG00158

Title

Denominators

Categories

Title	Measurements
	OG00054.9 OG00110.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		=0.0001		Odds Ratio (OR)	11.4739			2-Sided	95	3.3505	39.2931					Superiority

Secondary

Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study

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

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

Posted

Number

Percentage of participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value

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

MITT Population. Only participants with available data were analyzed.

Posted

Number

Percentage of participants

Weeks 19 and 20

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group

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

MITT Population. Only participants with available data were analyzed.

Posted

Number

Percentage of participants

Weeks 19 and 20

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group

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

MITT Population. Only participants with available data were analyzed.

Posted

Number

Percentage of participants

Weeks 19 and 20

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group

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

MITT Population. Only participants with available data were analyzed.

Posted

Number

Percentage of participants

Weeks 19 and 20

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population

MITT Population. Only participants with available data were analyzed.

Posted

Number

Percentage of participants

Weeks 19 and 20

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Change From Baseline in Hemoglobin

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

g/dL

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts

Secondary

Absolute Values of Hemoglobin

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

g/dL

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Change From Baseline in Hematocrit

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

Percentage of red blood cells in blood

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Absolute Values of Hematocrit

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

Percentage of red blood cells in blood

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Change From Baseline in Red Blood Cell Count

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

10^6 cells per microliter

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Absolute Values of Red Blood Cell Count

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

10^6 cells per microliter

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Change From Baseline in Reticulocyte Count

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

10^6 cells per microliter

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Absolute Values of Reticulocyte Count

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

10^6 cells per microliter

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

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Percentage of Participants Who Received ESA Rescue

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

MITT Population. Only participants with available data were analyzed.

Posted

Number

Percentage of participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Mean Number of ESA Rescue Doses Administered Per Participant

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

Doses/participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue

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

MITT Population. Only participants with available data were analyzed.

Posted

Number

Percentage of participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Number of Packed Red Blood Cell Transfusion Administered Per Participant

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

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

Posted

Median

Full Range

Units of blood per participant

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Time to First Transfusion or ESA Rescue Medication Intake

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

MITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

Weeks

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)

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

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

Posted

Count of Participants

Participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Secondary

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values

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

ITT Population

Posted

Count of Participants

Participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

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

ITT Population

Posted

Count of Participants

Participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings

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

ITT Population

Posted

Count of Participants

Participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Secondary

Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings

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

ITT Population

Posted

Count of Participants

Participants

Up to 20 Weeks

ID	Title	Description
OG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
OG001	Placebo	Participants were randomized to receive matching Placebo administered as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.

Units	Counts
Participants

Other Pre-specified

Exploratory: Change From Baseline in Iron and Total Iron Binding Capacity (TIBC)

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Transferrin

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Transferrin Saturation

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Mean Weekly Dose of Intravenous Elemental Iron Administered

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Iron and Total Iron Binding Capacity (TIBC)

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Transferrin

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Transferrin Saturation

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Reticulocyte Hemoglobin Content

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Reticulocyte Hemoglobin Content

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Hemoglobin A1c

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Hemoglobin A1c

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Lipids

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Lipids

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Hepcidin

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Hepcidin

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Vascular Endothelial Growth Factor (VEGF)

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Absolute Values of Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Change From Baseline in Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Neurocognitive Functioning as a Measure

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Patient-Reported Outcome Measures

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites

Not Posted

Baseline and up to Week 20

Participants

Other Pre-specified

Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites

Not Posted

Baseline

Participants

Facility	Status	City	State	ZIP	Country	Contacts
		Glendale	Arizona		United States

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.	3	138	33	138	58	138
EG001	Placebo	Participants received matching Placebo, as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.	0	72	11	72	29	72

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANGINA UNSTABLE	Cardiac disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
CARDIAC ARREST	Cardiac disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
MYOCARDIAL ISCHAEMIA	Cardiac disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
VERTIGO	Ear and labyrinth disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
IRRITABLE BOWEL SYNDROME	Gastrointestinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
SMALL INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
ASTHENIA	General disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
FATIGUE	General disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
SUDDEN CARDIAC DEATH	General disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	General disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
ANGIOEDEMA	Immune system disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
CELLULITIS	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
CRYPTOSPORIDIOSIS INFECTION	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
GASTROENTERITIS	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
OSTEOMYELITIS	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
PNEUMONIA	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0002 affected138 at risk EG0011 affected72 at risk
PNEUMONIA INFLUENZAL	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
UROSEPSIS	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
CEREBRAL HAEMORRHAGE TRAUMATIC	Injury, poisoning and procedural complications	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
LIVER FUNCTION TEST ABNORMAL	Investigations	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
DIABETES MELLITUS INADEQUATE CONTROL	Metabolism and nutrition disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
FLUID OVERLOAD	Metabolism and nutrition disorders	MedDra VERSION 15.1	Systematic Assessment	EG0002 affected138 at risk EG0011 affected72 at risk
HYPERKALAEMIA	Metabolism and nutrition disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
CEREBROVASCULAR ACCIDENT	Nervous system disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
DIABETIC AUTONOMIC NEUROPATHY	Nervous system disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
HYPOGLYCAEMIC UNCONSCIOUSNESS	Nervous system disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
PRESYNCOPE	Nervous system disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
MENTAL STATUS CHANGES	Psychiatric disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0011 affected72 at risk
DIABETIC NEPHROPATHY	Renal and urinary disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
GOODPASTURE'S SYNDROME	Renal and urinary disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
KIDNEY FIBROSIS	Renal and urinary disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
RENAL FAILURE ACUTE	Renal and urinary disorders	MedDra VERSION 15.1	Systematic Assessment	EG0007 affected138 at risk EG0012 affected72 at risk
RENAL FAILURE CHRONIC	Renal and urinary disorders	MedDra VERSION 15.1	Systematic Assessment	EG0006 affected138 at risk EG0010 affected72 at risk
RENAL TUBULAR NECROSIS	Renal and urinary disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
ACUTE RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG0002 affected138 at risk EG0010 affected72 at risk
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	Respiratory, thoracic and mediastinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG0000 affected138 at risk EG0011 affected72 at risk
ACCELERATED HYPERTENSION	Vascular disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
HYPERTENSION	Vascular disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk
PERIPHERAL VASCULAR DISORDER	Vascular disorders	MedDra VERSION 15.1	Systematic Assessment	EG0001 affected138 at risk EG0010 affected72 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG00014 affected138 at risk EG0013 affected72 at risk
Nausea	Gastrointestinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG00014 affected138 at risk EG0013 affected72 at risk
Constipation	Gastrointestinal disorders	MedDra VERSION 15.1	Systematic Assessment	EG0005 affected138 at risk EG0014 affected72 at risk
Fatigue	General disorders	MedDra VERSION 15.1	Systematic Assessment	EG00011 affected138 at risk EG0015 affected72 at risk
Oedema peripheral	General disorders	MedDra VERSION 15.1	Systematic Assessment	EG00010 affected138 at risk EG0017 affected72 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0002 affected138 at risk EG0015 affected72 at risk
Urinary tract infection	Infections and infestations	MedDra VERSION 15.1	Systematic Assessment	EG0008 affected138 at risk EG0016 affected72 at risk
Headache	Nervous system disorders	MedDra VERSION 15.1	Systematic Assessment	EG0008 affected138 at risk EG0012 affected72 at risk
Dizziness	Nervous system disorders	MedDra VERSION 15.1	Systematic Assessment	EG0007 affected138 at risk EG0013 affected72 at risk
Hypertension	Vascular disorders	MedDra VERSION 15.1	Systematic Assessment	EG00011 affected138 at risk EG0012 affected72 at risk
Hypotension	Vascular disorders	MedDra VERSION 15.1	Systematic Assessment	EG0006 affected138 at risk EG0014 affected72 at risk

ID	Term
D000740	Anemia
D051436	Renal Insufficiency, Chronic
D051437	Renal Insufficiency

ID	Title	Description
BG000	Vadadustat	Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels.
BG001	Placebo	Participants received matching Placebo, as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels.
BG002	Total	Total of all reporting groups

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms