42-Day Repeat Oral Dose Study of AKB-6548 in Participants... | NCT01381094

Label	Type	Intervention Names
AKB-6548 240 mg	Experimental	Drug: AKB-6548
AKB-6548 370 mg	Experimental	Drug: AKB-6548
AKB-6548 500 mg	Experimental	Drug: AKB-6548
AKB-6548 630 mg	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 42 days	AKB-6548 240 mg AKB-6548 370 mg AKB-6548 500 mg AKB-6548 630 mg

Measure	Description	Time Frame
Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)	Absolute change from Baseline was calculated as the Week 6 (end of treatment) value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing. If there was only one measurement prior to dosing, this measurement served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.	Baseline, Week 6

Measure	Description	Time Frame
Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.

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.
28343225	Derived	Martin ER, Smith MT, Maroni BJ, Zuraw QC, deGoma EM. Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease. Am J Nephrol. 2017;45(5):380-388. doi: 10.1159/000464476. Epub 2017 Mar 25.

ID	Title	Description
FG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
FG001	AKB-6548 370 mg

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

Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)

Absolute change from Baseline was calculated as the Week 6 (end of treatment) value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing. If there was only one measurement prior to dosing, this measurement served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.

Modified intent-to-treat (MITT) population: All randomized participants who received at least one dose of study medication and had a Baseline (both Screening and Baseline for Hgb and red blood cells [RBC] count) and at least one post-baseline measurement. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

Grams per deciliter (g/dL)

Baseline, Week 6

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003	AKB-6548 630 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 630 mg capsule QD for 42 days.
OG004	Placebo	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of matching Placebo QD for 42 days.

Units	Counts
Participants	OG00018 OG00116 OG00217 OG003

Title	Denominators	Categories
Baseline	ParticipantsOG00018 ParticipantsOG00116 ParticipantsOG00217 ParticipantsOG003

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 OG004						Mean Difference (Net)	0.80			2-Sided	95	0.24	1.35					Superiority
OG001 OG004

Secondary

Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

g/dL

Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated HCT concentration increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

Percentage of red blood cells in blood

Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated RBC count increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

10^6 cells/microliter (10^6 cells/μL)

Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte count increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

10^6 cells/μL

Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Reticulocyte Hgb Content at Week 6

Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte Hgb content increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

Picogram

Baseline, Week 6

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Maximum Change From Baseline in Hgb

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

g/dL

Baseline; up to Week 8

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003

Secondary

Maximum Change From Baseline in HCT

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that HCT concentration increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

Percentage of red blood cells

Baseline; up to Week 8

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003

Secondary

Maximum Change From Baseline in RBC Count

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that RBC count increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

10^6 cells/μL

Baseline; up to Week 8

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003

Secondary

Maximum Change in Absolute Reticulocyte Count From Baseline

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline absolute reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that reticulocyte count increased.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

10^6 cells/μL

Baseline; up to Week 8

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period

MITT population. Participants with available data were included in the analysis.

Posted

Count of Participants

Participants

Up to Week 6 (End of the Dosing Period)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period

MITT population. Participants with available data were included in the analysis.

Posted

Count of Participants

Participants

Up to Week 6 (End of The Dosing Period)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003

Secondary

Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period

MITT population. Participants with available data were included in the analysis.

Posted

Count of Participants

Participants

Up to Week 6 (End of The Dosing Period)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003

Secondary

Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period

MITT population. Participants with available data were included in the analysis.

Posted

Count of Participants

Participants

Up to Week 6 (End of The Dosing Period)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline reticulocytes count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

MITT population. Participants with available data were included in the analysis.

Posted

Count of Participants

Participants

Up to Week 6 (End of The Dosing Period)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline total iron was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

Micrograms per deciliter (µg/dL)

Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Unsaturated Iron Binding Capacity was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

µg/dL

Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron saturation was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

Percentage of saturation

Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

µg/dL

Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

Nanograms per milliliter (ng/mL)

Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline erythropoietin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

Intent-to-treat (ITT) population: All randomized participants who received at least one dose of study medication. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

ng/mL

Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.

Secondary

Change From Baseline in Hepcidin at Week 6

Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline hepcidin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

MITT population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

ng/mL

Baseline, Week 6

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003	AKB-6548 630 mg

Secondary

Mean Plasma Vadadustat Concentrations on Week 2 and Week 4

Plasma samples were collected for the analysis.

Pharmacokinetic (PK) Population: All participants in the ITT population that had pre-dose PK sampling that fell within a range of 18 to 30 hours after the previous dose of study medication or post-dose PK sampling that fell in a range of 2 to 8 hours post-dose. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

μg/mL

Week 2: Pre-dose and post-dose; Week 4: Pre-dose

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003

Secondary

Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4

Plasma samples were collected for the analysis.

PK population. Participants with available data were included in the analysis.

Posted

Mean

Standard Deviation

μg/mL

Week 2: Pre-dose; Week 4: Pre-dose

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003	AKB-6548 630 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 630 mg capsule QD for 42 days.

Secondary

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

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

ITT population.

Posted

Count of Participants

Participants

Up to Week 8 (Follow-up Visit 2 weeks after last dose)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.

Secondary

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

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

ITT population.

Posted

Count of Participants

Participants

Up to Week 8 (Follow-up Visit 2 weeks after last dose)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003	AKB-6548 630 mg

Secondary

Number of Participants With Clinically Significant Abnormal 12-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. Clinical significance is determined by the investigator. The investigator was responsible for reviewing laboratory results for clinical significance.

ITT population.

Posted

Count of Participants

Participants

Up to Week 8 (Follow-up Visit 2 weeks after last dose)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003

Secondary

Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval

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 parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected).

ITT population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline, Week 6

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003	AKB-6548 630 mg

Secondary

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

Parameters assessed for laboratory values included hematology, serum chemistry, C-reactive protein, DHEA-S, VEGF, and cystatin C. The investigator was responsible for reviewing laboratory results for clinically significant changes.

ITT population.

Posted

Count of Participants

Participants

Up to Week 8 (Follow-up Visit 2 weeks after last dose)

ID	Title	Description
OG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
OG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
OG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
OG003	AKB-6548 630 mg

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG0030 affected19 at risk EG0042 affected19 at risk
Neutropenia	Blood and lymphatic system disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Palpitations	Cardiac disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Ear haemorrhage	Ear and labyrinth disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Vision blurred	Eye disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Constipation	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0011 affected18 at risk EG0021 affected17 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0021 affected17 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Frequent bowel movements	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Nausea	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0011 affected18 at risk EG0022 affected17 at risk EG003
Vomiting	Gastrointestinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Adverse drug reaction	General disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Fatigue	General disorders	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Oedema	General disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Pain	General disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Bronchitis	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Ear infection	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Nasopharyngitis	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Pneumonia	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Urinary tract infection	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0002 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Viral infection	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Wound infection pseudomonas	Infections and infestations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Joint sprain	Injury, poisoning and procedural complications	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Muscle strain	Injury, poisoning and procedural complications	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Blood bicarbonate decreased	Investigations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Blood glucose decreased	Investigations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Blood uric acid increased	Investigations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Transferrin saturation decreased	Investigations	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Gout	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0023 affected17 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Vitamin d deficiency	Metabolism and nutrition disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Dizziness	Nervous system disorders	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Headache	Nervous system disorders	MedDra 13.0	Systematic Assessment	EG0002 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Presyncope	Nervous system disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Nocturia	Renal and urinary disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Renal impairment	Renal and urinary disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Eczema asteatotic	Skin and subcutaneous tissue disorders	MedDra 13.0	Systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Hypertension	Vascular disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hypotension	Vascular disorders	MedDra 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Pine Bluff	Arkansas		United States

ID	Term
D000740	Anemia
D007674	Kidney Diseases
D051436	Renal Insufficiency, Chronic
D051437	Renal Insufficiency

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic 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

ID	Title	Description
BG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.
BG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.
BG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.
BG003	AKB-6548 630 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 630 mg capsule QD for 42 days.
BG004	Placebo	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of matching Placebo QD for 42 days.
BG005	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AKB-6548 240 mg	Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days.	0	18	2	18	9	18
EG001	AKB-6548 370 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days.	1	18	3	18	5	18
EG002	AKB-6548 500 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days.	0	17	1	17	8	17
EG003	AKB-6548 630 mg	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 630 mg capsule QD for 42 days.	0	19	1	19	11	19
EG004	Placebo	Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of matching Placebo QD for 42 days.	0	19	1	19	11	19

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery disease	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG0030 affected19 at risk EG0040 affected19 at risk
Gastroenteritis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected17 at risk EG003
Azotaemia	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003
Cardiac pacemaker replacement	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected17 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected17 at risk EG003