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

• Sponsor: Akebia Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01235936
• Collaborator: (none)
• Enrollment: 10
• Locations: 2
• Arm: 1
• Duration (Months): 6.3
• Patients Per Site: 5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, pharmacodynamics and pharmacokinetics of repeat doses of orally administered AKB-6548 in pre-dialysis participants with anemia.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Kidney Disease	Drug: AKB-6548	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2a Open-Label Pilot Study to Assess the Pharmacodynamic Response, Pharmacokinetics, Safety, and Tolerability of 28-Day Repeat Oral Doses of AKB-6548 in Subjects With Anemia Secondary to Chronic Kidney Disease (CKD), Stages 3 and/or 4
• Study Start Date: Oct 21, 2010
• Actual Primary Completion Date: Apr 13, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AKB-6548	Drug: AKB-6548; Different dose levels

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Hemoglobin (Hgb) on Day 29 [Baseline; Day 29]

   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.

Secondary Outcome Measures

1. Mean Change From Baseline in Hematocrit on Day 29 [Baseline; Day 29]

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

2. Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29 [Baseline; Day 29]

   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.

3. Mean Change From Baseline in Absolute Reticulocyte Count on Day 29 [Baseline; Day 29]

   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.

4. Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29 [Baseline; Day 29]

   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.

5. Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 [Day 29]

   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).

6. Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 [Day 29]

   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).

7. Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 [Day 29]

   Blood samples were collected to assess hematocrit.

8. Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 [Day 29]

   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).

9. Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 [Day 29]

   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).

10. Change From Baseline in Ferritin on Day 29 [Baseline; Day 29]

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

11. Change From Baseline in Iron on Day 29 [Baseline; Day 29]

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

12. Change From Baseline in Total Iron Binding Capacity on Day 29 [Baseline; Day 29]

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

13. Change From Baseline in Transferrin Saturation on Day 29 [Baseline; Day 29]

    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.

14. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Up to 2 weeks post 28 days of treatment]

    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.

15. Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values [Up to 2 weeks post 28 days of treatment]

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

16. Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values [Up to 2 weeks post 28 days of treatment]

    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.

17. Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings [Up to 2 weeks post 28 days of treatment]

    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.

18. Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval [Up to 2 weeks post 28 days of treatment]

    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).

19. Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 [Pre-dose at Day 8, 15, 22 and 29]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• 18 to 79 years of age, inclusive

• Chronic Kidney Disease Stage 3 or Stage 4

• Hemoglobin (Hgb) < 10.5 g/dl

• TSAT > 20% and CBC indicating normocytic red blood cell morphology

Key Exclusion Criteria:

• BMI > 40

• Red blood cell transfusion within 12 weeks.

• Androgen therapy within the previous 21 days prior to study dosing

• Therapy with any approved or experimental erythropoiesis stimulating agent (ESA) within the 10 weeks prior to the Screening visit

• Participants meeting the criteria of ESA resistance within the previous 4 months

• Individual doses of intravenous iron of 250 mg or larger within the past 21 days

• AST or ALT >1.8x ULN.

• Alkaline phosphatase >2x ULN.

• Total bilirubin >1.5x ULN.

• Uncontrolled hypertension

• New York Heart Association Class III or IV congestive heart failure

• Myocardial infarction, acute coronary syndrome, or stroke within 6 months prior to dosing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Augusta	Georgia	United States
2		San Antonio	Texas	United States

Sponsors and Collaborators

• Akebia Therapeutics

Investigators

• Study Director: Chief Medical Officer, Akebia Therapeutics Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Akebia Therapeutics
• ClinicalTrials.gov Identifier: NCT01235936
• Other Study ID Numbers: AKB-6548-CI-0004
• First Posted: Nov 8, 2010
• Last Update Posted: Jul 1, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Akebia Therapeutics: anemia; chronic kidney disease; CKD; chronic renal insufficiency; renal impairment; erythropoietin; safety; efficacy; tolerability; pharmacokinetics
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Vadadustat
Arm/Group Description	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 Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.1 (11.8)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%
Not Hispanic or Latino	9 90%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 50%
White	4 40%
More than one race	0 0%
Unknown or Not Reported	1 10%
Kidney disease stage (Count of Participants)
Stage 3	6 60%
Stage 4	4 40%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Hemoglobin (Hgb) on Day 29
Description	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.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	9.91 (0.63)
Change from Baseline on Day 29	0.63 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The primary endpoint was compared using the Wilcoxon signed-rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Wilcoxon signed rank test
	Comments

2. Secondary Outcome

Title	Mean Change From Baseline in Hematocrit on Day 29
Description	Blood samples were collected to assess hematocrit. A positive change from baseline indicates hematocrit concentration increased.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	30.43 (2.69)
Change from Baseline on Day 29	1.62 (1.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	=0.0156
	Comments
	Method	Wilcoxon signed rank test
	Comments

3. Secondary Outcome

Title	Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29
Description	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.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	3.313 (0.389)
Change from Baseline on Day 29	0.167 (0.170)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	0.0098
	Comments
	Method	Wilcoxon signed rank test
	Comments

4. Secondary Outcome

Title	Mean Change From Baseline in Absolute Reticulocyte Count on Day 29
Description	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.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	51076.00 (24975.76)
Change from Baseline on Day 29	18647.00 (18289.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	=0.0195
	Comments
	Method	Wilcoxon signed rank test
	Comments

5. Secondary Outcome

Title	Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29
Description	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.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	31.49 (2.44)
Change from Baseline on Day 29	0.13 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	=0.8262
	Comments
	Method	Wilcoxon signed rank test
	Comments

6. Secondary Outcome

Title	Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29
Description	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).
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Change from baseline ≥ 0.4 grams per decilitre	6 60%
Change from baseline ≥ 0.6 grams per decilitre	5 50%
Change from baseline ≥ 0.8 grams per decilitre	3 30%
Change from baseline ≥ 1.0 grams per decilitre	2 20%

7. Secondary Outcome

Title	Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29
Description	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).
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Percent change from Baseline ≥ 5.0%	5 50%
Percent change from Baseline ≥ 7.5%	3 30%
Percent change from Baseline ≥ 10.0%	3 30%

8. Secondary Outcome

Title	Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29
Description	Blood samples were collected to assess hematocrit.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Percent change from Baseline ≥ 5.0%	6 60%
Percent change from Baseline ≥ 7.5%	2 20%
Percent change from Baseline ≥ 10.0%	2 20%

9. Secondary Outcome

Title	Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29
Description	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).
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Percent change from Baseline ≥ 5.0%	5 50%
Percent change from Baseline ≥ 7.5%	3 30%
Percent change from Baseline ≥ 10.0%	3 30%

10. Secondary Outcome

Title	Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29
Description	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).
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Change from Baseline ≥ 6000 cells per microlitre	8 80%
Change from Baseline ≥ 12000 cells per microlitre	7 70%
Change from Baseline ≥ 18000 cells per microlitre	6 60%

11. Secondary Outcome

Title	Change From Baseline in Ferritin on Day 29
Description	Blood samples were collected to assess ferritin. A positive change from baseline indicates ferritin content increased.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	324.0 (199.2)
Change from Baseline on Day 29	-52.3 (36.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	=0.0020
	Comments
	Method	Wilcoxon signed rank test
	Comments

12. Secondary Outcome

Title	Change From Baseline in Iron on Day 29
Description	Blood samples were collected to assess iron. A positive change from baseline indicates iron content increased.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	69.4 (18.4)
Change from Baseline on Day 29	-8.2 (20.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	=0.2383
	Comments
	Method	Wilcoxon signed rank test
	Comments

13. Secondary Outcome

Title	Change From Baseline in Total Iron Binding Capacity on Day 29
Description	Blood samples were collected to assess total iron binding capacity. A positive change from baseline indicates total iron binding capacity increased.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	266.4 (56.4)
Change from Baseline on Day 29	43.4 (34.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	=0.0039
	Comments
	Method	Wilcoxon signed rank test
	Comments

14. Secondary Outcome

Title	Change From Baseline in Transferrin Saturation on Day 29
Description	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.
Time Frame	Baseline; Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline	26.1 (6.3)
Change from Baseline on Day 29	-6.4 (5.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vadadustat
	Comments	Analysis of change from baseline on Day 29
	Type of Statistical Test	Other
	Comments	The test was based on Wilcoxon signed rank test, with an alpha level of 0.05.
Statistical Test of Hypothesis	p-Value	=0.0039
	Comments
	Method	Wilcoxon signed rank test
	Comments

15. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Up to 2 weeks post 28 days of treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
TEAEs	5 50%
SAEs	0 0%
Deaths	0 0%

16. Secondary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Description	Parameters assessed for laboratory values included hematology, chemistry, urinalysis, and coagulation. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time Frame	Up to 2 weeks post 28 days of treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Count of Participants [Participants]	0 0%

17. Secondary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
Description	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.
Time Frame	Up to 2 weeks post 28 days of treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Count of Participants [Participants]	0 0%

18. Secondary Outcome

Title	Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
Description	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.
Time Frame	Up to 2 weeks post 28 days of treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Count of Participants [Participants]	0 0%

19. Secondary Outcome

Title	Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Description	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).
Time Frame	Up to 2 weeks post 28 days of treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Baseline PR Interval	183.2 (42.6)
Change from Baseline PR Interval	-4.4 (18.1)
Baseline QT Interval	415.6 (45.7)
Change from Baseline QT Interval	1.4 (20.3)
Baseline QRS Interval	95.4 (21.4)
Change from Baseline QRS Interval	3.4 (6.7)
Baseline QTC Interval	429.9 (30.5)
Change from Baseline QTC Interval	4.1 (8.3)

20. Secondary Outcome

Title	Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29
Description	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
Time Frame	Pre-dose at Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vadadustat
Arm/Group Description	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.
Measure Participants	10
Day 8	3260.6 (2763.8)
Day 15	3826.3 (2537.5)
Day 22	3667.4 (1933.4)
Day 29	5622.4 (5385.4)

Adverse Events

Time Frame	Up to 2 weeks post 28 days of treatment
Adverse Event Reporting Description	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.
Arm/Group Title	Vadadustat
Arm/Group Description	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.
All Cause Mortality
	Vadadustat
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Vadadustat
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Vadadustat
	Affected / at Risk (%)	# Events
Total	5/10 (50%)
Gastrointestinal disorders
Constipation	1/10 (10%)
Diarrhoea	2/10 (20%)
Dyspepsia	1/10 (10%)
Nausea	1/10 (10%)
General disorders
Chills	1/10 (10%)
Fatigue	1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	1/10 (10%)
Hyperkalaemia	1/10 (10%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/10 (10%)
Nervous system disorders
Dizziness	1/10 (10%)
Headache	1/10 (10%)
Neuropathy peripheral	1/10 (10%)
Peripheral sensory neuropathy	1/10 (10%)

Limitations/Caveats

This pilot study planned to include 15 participants with either Stage 3 or 4 CKD, with no minimum or maximum enrollment target for either stage; however, because of slow enrollment the Sponsor terminated the study early after only 10 participants had enrolled. The overall status of the study was considered as completed since 10 participants received Vadadustat and all 10 participants completed the study per protocol.

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.