Trial Evaluating the Efficacy and Safety of Oral Vadadust... | NCT04313153

NCT04313153

ID	Type	Description	Link
AKB-6548-CI-0036	Other Identifier	Akebia Protocol Number
2019-004851-36	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Otsuka Pharmaceutical Development & Commercialization, Inc.	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Vadadustat once daily (QD)	Experimental	Drug: Vadadustat
Vadadustat three times weekly (TIW)	Experimental	Drug: Vadadustat
Darbepoetin alfa	Active Comparator	Drug: Darbepoetin alfa

Name	Type	Description	Arm Group Labels	Other Names
Vadadustat	Drug	oral tablets	Vadadustat once daily (QD) Vadadustat three times weekly (TIW)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)	The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26, regardless of intercurrent events. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.	Baseline; Weeks 20 to 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)	The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the SEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 46 through 52, regardless of intercurrent events. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as SEP value minus the Baseline value.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Receiving chronic, outpatient three times weekly (TIW) in-center hemodialysis for end-stage renal disease for at least 12 weeks prior to Screening
Hemodialysis adequacy as indicated by single-pool Kt/Vurea ≥ 1.2 using the most recent historical measurement within 8 weeks prior to or during Screening
Use of any approved erythropoiesis-stimulating agents (ESAs) for at least the 8 weeks prior to Screening Visit 2
Two hemoglobin (Hb) values, at least 4 days apart, measured by the central laboratory during Screening within the following prespecified ranges:
1. Hb values between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States;
2. Hb values between 9.0 and 12.0 g/dL (inclusive) in Europe
Serum ferritin ≥ 100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥ 20% during Screening
Folate and vitamin B12 measurements ≥ lower limit of normal during Screening

Exclusion Criteria:

Anemia due to a cause other than chronic kidney disease (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)
Participants meeting cut-off of the following equivalent mean weekly doses calculated over 8 weeks prior to Screening Visit 2
1. Methoxy polyethylene glycol-epoetin beta > 50 micrograms (µg)/week;
2. Darbepoetin alfa > 100 µg/week;
3. Epoetin analogues > 23000 International Units (IU)/week
Active bleeding or recent blood loss within 8 weeks prior to randomization
Red blood cell transfusion within 8 weeks prior to randomization
Current uncontrolled hypertension.
Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening.
Known hypersensitivity to vadadustat, darbepoetin alfa, or any of their excipients

Contacts/Locations Module

Name	Affiliation	Role
Chief Medical Officer	Akebia Therapeutics	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Chula Vista	California	91910	United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39231617	Derived	Kooienga L, Burke S, Kathresal A, Luo W, Yang Z, Zhang Z, Zwiech R, Hernandez GT. Safety and Efficacy of Vadadustat Once Daily and Three Times Weekly in Patients With Dialysis-Dependent CKD With Anemia. Kidney360. 2024 Nov 1;5(11):1652-1661. doi: 10.34067/KID.0000000567. Epub 2024 Sep 4.
36005278	Derived

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Vadadustat QD	Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED	Randomized Population is defined as all participants who were randomized in the study have been presented in Participant Flow

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 17, 2021	Sep 3, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Randomized Population is defined as all participants randomized.

Arm/Group Information

ID	Title	Description
BG000	Vadadustat QD	Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.
BG001	Vadadustat TIW	Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.
BG002	Darbepoetin Alfa	Participants were randomized to receive darbepoetin alfa as a solution in single-dose prefilled syringes via intravenous (IV) injection through dialysis vascular access. For participants who had received darbepoetin alfa during screening, the initial dosing regimen was approximately the same weekly dose that they were receiving prior to randomization. For participants who had received darbepoetin alfa for the first time, the initial dosing regimen was determined by the United States Package Insert (USPI) or European Union Summary of product characteristics (EU SmPC), per the medical judgment of the investigator.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00060.9± 13.4 BG00161.2± 12.5 BG00260.8± 12.8 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00047 BG00146 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00023 BG00136 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG0001 BG0012 BG002

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

Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)

The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26, regardless of intercurrent events. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.

Randomized Population

Posted

Least Squares Mean

Standard Error

Grams per deciliter (g/dL)

Baseline; Weeks 20 to 26

ID	Title	Description
OG000	Vadadustat QD	Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.
OG001	Vadadustat TIW	Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.
OG002	Darbepoetin Alfa	Participants were randomized to receive darbepoetin alfa as a solution in single-dose prefilled syringes via intravenous (IV) injection through dialysis vascular access. For participants who had received darbepoetin alfa during screening, the initial dosing regimen was approximately the same weekly dose that they were receiving prior to randomization. For participants who had received darbepoetin alfa for the first time, the initial dosing regimen was determined by the United States Package Insert (USPI) or European Union Summary of product characteristics (EU SmPC), per the medical judgment of the investigator.

Units	Counts
Participants	OG000105 OG001106 OG002108

Title

Denominators

Categories

Title	Measurements
	OG0000.07± 0.12 OG001-0.19± 0.12 OG0020.34± 0.12

Secondary

Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)

The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the SEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 46 through 52, regardless of intercurrent events. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as SEP value minus the Baseline value.

Randomized Population

Posted

Least Squares Mean

Standard Error

g/dL

Baseline; Weeks 46 to 52

ID	Title	Description
OG000	Vadadustat QD	Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.
OG001	Vadadustat TIW

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Vadadustat QD	Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.	12	105	47	105	46	105
EG001	Vadadustat TIW	Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.	9	104	47	104	49	104
EG002	Darbepoetin Alfa	Participants were randomized to receive darbepoetin alfa as a solution in single-dose prefilled syringes via intravenous (IV) injection through dialysis vascular access. For participants who had received darbepoetin alfa during screening, the initial dosing regimen was approximately the same weekly dose that they were receiving prior to randomization. For participants who had received darbepoetin alfa for the first time, the initial dosing regimen was determined by the United States Package Insert (USPI) or European Union Summary of product characteristics (EU SmPC), per the medical judgment of the investigator.	7	108	47	108	46	108

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDra 25	Systematic Assessment	EG0003 affected105 at risk EG0015 affected104 at risk EG0025 affected108 at risk
Blood loss anaemia	Blood and lymphatic system disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0012 affected104 at risk EG0020 affected108 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Acute left ventricular failure	Cardiac disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Acute myocardial infarction	Cardiac disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0016 affected104 at risk EG0020 affected108 at risk
Angina pectoris	Cardiac disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Atrial fibrillation	Cardiac disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0012 affected104 at risk EG0021 affected108 at risk
Atrial flutter	Cardiac disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Atrioventricular block complete	Cardiac disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Cardiac arrest	Cardiac disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0012 affected104 at risk EG0021 affected108 at risk
Cardiac failure	Cardiac disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Cardiac failure acute	Cardiac disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Cardiac failure congestive	Cardiac disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0012 affected104 at risk EG0021 affected108 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Coronary artery disease	Cardiac disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Myocardial infarction	Cardiac disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0013 affected104 at risk EG0021 affected108 at risk
Pericardial effusion	Cardiac disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Haemorrhagic arteriovenous malformation	Congenital, familial and genetic disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Hyperparathyroidism secondary	Endocrine disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Parathyroid hyperplasia	Endocrine disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Visual impairment	Eye disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Vitreous haemorrhage	Eye disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Chronic gastritis	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Duodenitis	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Food poisoning	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Gastritis haemorrhagic	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0013 affected104 at risk EG0020 affected108 at risk
Haematochezia	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Pancreatic duct obstruction	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0012 affected104 at risk EG0020 affected108 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0022 affected108 at risk
Asthenia	General disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Non-cardiac chest pain	General disorders	MedDra 25	Systematic Assessment	EG0003 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Sudden cardiac death	General disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Bile duct stenosis	Hepatobiliary disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Contrast media allergy	Immune system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Kidney transplant rejection	Immune system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0022 affected108 at risk
Arthritis bacterial	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Asymptomatic COVID-19	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
COVID-19	Infections and infestations	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0012 affected104 at risk EG0024 affected108 at risk
COVID-19 pneumonia	Infections and infestations	MedDra 25	Systematic Assessment	EG0007 affected105 at risk EG0018 affected104 at risk EG0024 affected108 at risk
Candida pneumonia	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Cellulitis	Infections and infestations	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0012 affected104 at risk EG0022 affected108 at risk
Cryptococcal fungaemia	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Device related bacteraemia	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Device related sepsis	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Diabetic foot infection	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Diverticulitis	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0022 affected108 at risk
Diverticulitis intestinal haemorrhagic	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Endocarditis	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Enterococcal bacteraemia	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Gangrene	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0022 affected108 at risk
Klebsiella sepsis	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0022 affected108 at risk
Muscle abscess	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Necrotising soft tissue infection	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Osteomyelitis	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0022 affected108 at risk
Otitis media staphylococcal	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Peritonitis bacterial	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Pneumonia	Infections and infestations	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0013 affected104 at risk EG0021 affected108 at risk
Pneumonia aspiration	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Pneumonia staphylococcal	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Renal abscess	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
SARS-CoV-2 sepsis	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Sepsis	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0013 affected104 at risk EG0023 affected108 at risk
Septic shock	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Staphylococcal osteomyelitis	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Staphylococcal sepsis	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Urinary tract infection	Infections and infestations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Vascular graft infection	Infections and infestations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Arteriovenous fistula site complication	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Arteriovenous fistula site haemorrhage	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Arteriovenous fistula thrombosis	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0012 affected104 at risk EG0023 affected108 at risk
Arteriovenous graft thrombosis	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Traumatic haematoma	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Traumatic haemothorax	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Vascular access site haemorrhage	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Alanine aminotransferase increased	Investigations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Anticoagulation drug level above therapeutic	Investigations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Aspartate aminotransferase increased	Investigations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Hepatic enzyme increased	Investigations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Liver function test increased	Investigations	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Transaminases increased	Investigations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Troponin increased	Investigations	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0023 affected108 at risk
Hypervolaemia	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0014 affected104 at risk EG0024 affected108 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0012 affected104 at risk EG0021 affected108 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0012 affected104 at risk EG0020 affected108 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Fracture pain	Musculoskeletal and connective tissue disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Adenocarcinoma of appendix	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Gastrointestinal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Liposarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Ataxia	Nervous system disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Bell's palsy	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Embolic stroke	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Encephalopathy	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Haemorrhagic stroke	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Ischaemic cerebral infarction	Nervous system disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Ischaemic stroke	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Myelopathy	Nervous system disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Presyncope	Nervous system disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Seizure	Nervous system disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Syncope	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Toxic encephalopathy	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Transient ischaemic attack	Nervous system disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Azotaemia	Renal and urinary disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
End stage renal disease	Renal and urinary disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Renal cyst haemorrhage	Renal and urinary disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Postmenopausal haemorrhage	Reproductive system and breast disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Uterine haemorrhage	Reproductive system and breast disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0003 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0012 affected104 at risk EG0021 affected108 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Intertrigo	Skin and subcutaneous tissue disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Arteriovenous fistula operation	Surgical and medical procedures	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Hypertensive crisis	Vascular disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0012 affected104 at risk EG0020 affected108 at risk
Hypertensive emergency	Vascular disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Hypertensive urgency	Vascular disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0021 affected108 at risk
Jugular vein thrombosis	Vascular disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk
Orthostatic hypotension	Vascular disorders	MedDra 25	Systematic Assessment	EG0000 affected105 at risk EG0011 affected104 at risk EG0021 affected108 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0012 affected104 at risk EG0020 affected108 at risk
Peripheral vascular disorder	Vascular disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0011 affected104 at risk EG0020 affected108 at risk
Steal syndrome	Vascular disorders	MedDra 25	Systematic Assessment	EG0001 affected105 at risk EG0010 affected104 at risk EG0020 affected108 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDra 25	Systematic Assessment	EG0005 affected105 at risk EG0017 affected104 at risk EG0027 affected108 at risk
Abdominal pain	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG0004 affected105 at risk EG0014 affected104 at risk EG0028 affected108 at risk
Diarrhoea	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG00014 affected105 at risk EG00115 affected104 at risk EG0026 affected108 at risk
Nausea	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG00012 affected105 at risk EG0016 affected104 at risk EG0026 affected108 at risk
Vomiting	Gastrointestinal disorders	MedDra 25	Systematic Assessment	EG00010 affected105 at risk EG0014 affected104 at risk EG0026 affected108 at risk
Oedema peripheral	General disorders	MedDra 25	Systematic Assessment	EG0006 affected105 at risk EG0010 affected104 at risk EG0023 affected108 at risk
COVID-19	Infections and infestations	MedDra 25	Systematic Assessment	EG00012 affected105 at risk EG00111 affected104 at risk EG00210 affected108 at risk
Fall	Injury, poisoning and procedural complications	MedDra 25	Systematic Assessment	EG00010 affected105 at risk EG0016 affected104 at risk EG0025 affected108 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0004 affected105 at risk EG0015 affected104 at risk EG0029 affected108 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 25	Systematic Assessment	EG0006 affected105 at risk EG0011 affected104 at risk EG0023 affected108 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDra 25	Systematic Assessment	EG0002 affected105 at risk EG0016 affected104 at risk EG0022 affected108 at risk
Hypertension	Vascular disorders	MedDra 25	Systematic Assessment	EG0006 affected105 at risk EG00111 affected104 at risk EG00210 affected108 at risk

Per the protocol, data was collected by the arm to which participants were randomized and not by dose received in vadadustat QD or vadadustat TIW arms.

Certain Agreements

First MCP Posted Date

ID	Term
D000740	Anemia

ID	Term
C000624313	vadadustat
D000068256	Darbepoetin alfa

Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
D004921	Erythropoietin
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins