Trial Outcomes & Findings for Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia (NCT NCT01235936)

NCT ID: NCT01235936

Last Updated: 2022-07-01

Results Overview

Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates that hemoglobin concentration increased.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: Baseline; Day 29
• Results posted on: 2022-07-01

Participant Flow

This study enrolled Chronic Kidney Disease (CKD) Stage 3 or CKD Stage 4 participants. Per protocol, this is a pilot study and all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state as the Sponsor terminated the study early after enrolling 10 participants.

Participant milestones

Measure	Vadadustat Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia

Baseline characteristics by cohort

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Age, Continuous	60.1 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Kidney disease stage Stage 3	6 Participants n=5 Participants
Kidney disease stage Stage 4	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline; Day 29

Population: Full Analysis Set: All participants who received at least 1 dose of study medication. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates that hemoglobin concentration increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Mean Change From Baseline in Hemoglobin (Hgb) on Day 29 Baseline	9.91 Grams per decilitre (g/dL) Standard Deviation 0.63
Mean Change From Baseline in Hemoglobin (Hgb) on Day 29 Change from Baseline on Day 29	0.63 Grams per decilitre (g/dL) Standard Deviation 0.46

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess hematocrit. A positive change from baseline indicates hematocrit concentration increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Mean Change From Baseline in Hematocrit on Day 29 Baseline	30.43 Percentage of red blood cells in blood Standard Deviation 2.69
Mean Change From Baseline in Hematocrit on Day 29 Change from Baseline on Day 29	1.62 Percentage of red blood cells in blood Standard Deviation 1.71

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates RBC count increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29 Baseline	3.313 Million cells per cubic millimeter Standard Deviation 0.389
Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29 Change from Baseline on Day 29	0.167 Million cells per cubic millimeter Standard Deviation 0.170

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline). A positive change from baseline indicates absolute reticulocyte count increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Mean Change From Baseline in Absolute Reticulocyte Count on Day 29 Baseline	51076.00 Cells per Microlitre Standard Deviation 24975.76
Mean Change From Baseline in Absolute Reticulocyte Count on Day 29 Change from Baseline on Day 29	18647.00 Cells per Microlitre Standard Deviation 18289.84

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess reticulocyte Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates reticulocyte Hgb content increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29 Baseline	31.49 Picograms Standard Deviation 2.44
Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29 Change from Baseline on Day 29	0.13 Picograms Standard Deviation 0.84

SECONDARY outcome

Timeframe: Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 Change from baseline ≥ 0.4 grams per decilitre	6 Participants
Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 Change from baseline ≥ 0.6 grams per decilitre	5 Participants
Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 Change from baseline ≥ 0.8 grams per decilitre	3 Participants
Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 Change from baseline ≥ 1.0 grams per decilitre	2 Participants

SECONDARY outcome

Timeframe: Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 Percent change from Baseline ≥ 5.0%	5 Participants
Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 Percent change from Baseline ≥ 7.5%	3 Participants
Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 Percent change from Baseline ≥ 10.0%	3 Participants

SECONDARY outcome

Timeframe: Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess hematocrit.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 Percent change from Baseline ≥ 5.0%	6 Participants
Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 Percent change from Baseline ≥ 7.5%	2 Participants
Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 Percent change from Baseline ≥ 10.0%	2 Participants

SECONDARY outcome

Timeframe: Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 Percent change from Baseline ≥ 5.0%	5 Participants
Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 Percent change from Baseline ≥ 7.5%	3 Participants
Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 Percent change from Baseline ≥ 10.0%	3 Participants

SECONDARY outcome

Timeframe: Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline).

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 Change from Baseline ≥ 6000 cells per microlitre	8 Participants
Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 Change from Baseline ≥ 12000 cells per microlitre	7 Participants
Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 Change from Baseline ≥ 18000 cells per microlitre	6 Participants

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess ferritin. A positive change from baseline indicates ferritin content increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Change From Baseline in Ferritin on Day 29 Baseline	324.0 Nanograms per millilitre Standard Deviation 199.2
Change From Baseline in Ferritin on Day 29 Change from Baseline on Day 29	-52.3 Nanograms per millilitre Standard Deviation 36.6

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess iron. A positive change from baseline indicates iron content increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Change From Baseline in Iron on Day 29 Baseline	69.4 Micrograms per decilitre Standard Deviation 18.4
Change From Baseline in Iron on Day 29 Change from Baseline on Day 29	-8.2 Micrograms per decilitre Standard Deviation 20.3

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess total iron binding capacity. A positive change from baseline indicates total iron binding capacity increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Change From Baseline in Total Iron Binding Capacity on Day 29 Baseline	266.4 Micrograms per decilitre Standard Deviation 56.4
Change From Baseline in Total Iron Binding Capacity on Day 29 Change from Baseline on Day 29	43.4 Micrograms per decilitre Standard Deviation 34.8

SECONDARY outcome

Timeframe: Baseline; Day 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Blood samples were collected to assess transferrin saturation. The transferrin saturation is the ratio of the serum iron concentration and the total iron-binding capacity, expressed as a percentage. A positive change from baseline indicates transferrin saturation increased.

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Change From Baseline in Transferrin Saturation on Day 29 Baseline	26.1 Percentage Standard Deviation 6.3
Change From Baseline in Transferrin Saturation on Day 29 Change from Baseline on Day 29	-6.4 Percentage Standard Deviation 5.4

SECONDARY outcome

Timeframe: Up to 2 weeks post 28 days of treatment

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

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

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAEs	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) SAEs	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Deaths	0 Participants

SECONDARY outcome

Timeframe: Up to 2 weeks post 28 days of treatment

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

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

Outcome measures

Measure

Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.

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

0 Participants

SECONDARY outcome

Timeframe: Up to 2 weeks post 28 days of treatment

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

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

Outcome measures

Measure

Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.

Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values

0 Participants

SECONDARY outcome

Timeframe: Up to 2 weeks post 28 days of treatment

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

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

Outcome measures

Measure

Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.

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

0 Participants

SECONDARY outcome

Timeframe: Up to 2 weeks post 28 days of treatment

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

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).

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Baseline PR Interval	183.2 Milliseconds Standard Deviation 42.6
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Change from Baseline PR Interval	-4.4 Milliseconds Standard Deviation 18.1
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Baseline QT Interval	415.6 Milliseconds Standard Deviation 45.7
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Change from Baseline QT Interval	1.4 Milliseconds Standard Deviation 20.3
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Baseline QRS Interval	95.4 Milliseconds Standard Deviation 21.4
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Change from Baseline QRS Interval	3.4 Milliseconds Standard Deviation 6.7
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Baseline QTC Interval	429.9 Milliseconds Standard Deviation 30.5
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Change from Baseline QTC Interval	4.1 Milliseconds Standard Deviation 8.3

SECONDARY outcome

Timeframe: Pre-dose at Day 8, 15, 22 and 29

Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Serum samples were collected from the participants at the defined time points. Trough concentration was defined as the concentration of drug in the blood immediately before the next dose is administered. Trough concentration was calculated using the validated liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method

Outcome measures

Measure	Vadadustat n=10 Participants Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 Day 8	3260.6 nanograms per millilitre Standard Deviation 2763.8
Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 Day 15	3826.3 nanograms per millilitre Standard Deviation 2537.5
Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 Day 22	3667.4 nanograms per millilitre Standard Deviation 1933.4
Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 Day 29	5622.4 nanograms per millilitre Standard Deviation 5385.4

Adverse Events

Vadadustat

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vadadustat n=10 participants at risk Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants.
Gastrointestinal disorders Constipation	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Gastrointestinal disorders Diarrhoea	20.0% 2/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Gastrointestinal disorders Dyspepsia	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Gastrointestinal disorders Nausea	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
General disorders Chills	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
General disorders Fatigue	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Metabolism and nutrition disorders Decreased appetite	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Metabolism and nutrition disorders Hyperkalaemia	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Nervous system disorders Dizziness	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Nervous system disorders Headache	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Nervous system disorders Neuropathy peripheral	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
Nervous system disorders Peripheral sensory neuropathy	10.0% 1/10 • Up to 2 weeks post 28 days of treatment Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

Additional Information

Akebia Therapeutics, Inc

Akebia Therapeutics, Inc

Phone: 617-844-6128

Email: trials@akebia.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place