Trial Outcomes & Findings for Study to Assess the Safety and Pharmacokinetics of AKB-6548 in Participants With Chronic Kidney Disease (CKD), Stages 3 and 4 (NCT NCT04707573)
NCT ID: NCT04707573
Last Updated: 2022-06-28
Results Overview
Plasma samples were collected from the participants at the defined time points. T½ was defined as apparent terminal elimination half-life. T½ was calculated using the standard non-compartmental method.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
22 participants
Primary outcome timeframe
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Results posted on
2022-06-28
Participant Flow
A total of 22 participants were enrolled in this study. The participants were placed in one of two cohorts, depending on disease state: Chronic Kidney Disease (CKD) Stage 3 (Cohort 1) or CKD Stage 4 (Cohort 2).
Participant milestones
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 milliliter (mL)/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
12
|
|
Overall Study
COMPLETED
|
10
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess the Safety and Pharmacokinetics of AKB-6548 in Participants With Chronic Kidney Disease (CKD), Stages 3 and 4
Baseline characteristics by cohort
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.0 years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
64.4 years
STANDARD_DEVIATION 10.0 • n=7 Participants
|
63.8 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Estimated Glomerular Filtration Rate
|
45.22 mL/min/1.73m^2
STANDARD_DEVIATION 8.54 • n=5 Participants
|
24.39 mL/min/1.73m^2
STANDARD_DEVIATION 3.31 • n=7 Participants
|
33.86 mL/min/1.73m^2
STANDARD_DEVIATION 12.23 • n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Day 8Population: Intent-to-treat (ITT) population: all enrolled participants who received a dose of the study drug.
An Adverse Event (AE) was defined as any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurring in a human being participating in a clinical study following study medication administration, regardless of causal relationship. This also included any clinically significant worsening or re-occurrence of a pre-existing condition, or AE occurring from an overdose of a study drug whether accidental or intentional or AE occurring from abuse of study drug or that has been associated with the discontinuation of the use of study drug.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
6 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Up to Day 8Population: ITT Population
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 |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Serum chemistry
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Urinalysis
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Hematology
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Coagulation
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Day 8Population: ITT Population
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. Number of participants with a clinically significant change from baseline in at least one of the assessed vital signs parameters is reported.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
|
2 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Day 2Population: ITT Population
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 |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline; Day 2Population: ITT Population
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). The baseline was defined as Day 1 pre-dose measurement. If missing, the last measurement prior to dosing was used.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Baseline PR interval
|
178.8 Milliseconds
Standard Deviation 44.2
|
182.5 Milliseconds
Standard Deviation 24.2
|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Change from Baseline at Day 2 PR interval
|
-12.4 Milliseconds
Standard Deviation 28.4
|
-3.5 Milliseconds
Standard Deviation 5.5
|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Baseline QRS interval
|
98.8 Milliseconds
Standard Deviation 20.7
|
97.7 Milliseconds
Standard Deviation 26.0
|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Change from Baseline at Day 2 QRS interval
|
-0.8 Milliseconds
Standard Deviation 3.2
|
0.0 Milliseconds
Standard Deviation 5.4
|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Baseline QT interval
|
427.2 Milliseconds
Standard Deviation 22.0
|
426.5 Milliseconds
Standard Deviation 39.7
|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Change from Baseline at Day 2 QT interval
|
-13.8 Milliseconds
Standard Deviation 21.8
|
-2.3 Milliseconds
Standard Deviation 16.7
|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Baseline QTc interval
|
423.5 Milliseconds
Standard Deviation 22.8
|
439.5 Milliseconds
Standard Deviation 35.8
|
|
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Change from Baseline at Day 2 QTc interval
|
3.1 Milliseconds
Standard Deviation 10.2
|
2.0 Milliseconds
Standard Deviation 18.2
|
PRIMARY outcome
Timeframe: Baseline; Day 2Population: ITT Population
The heart rate evaluation was performed after the participant had been resting comfortably in a supine position for approximately 10 minutes.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Change From Baseline in Heart Rate
Baseline
|
59.8 Beats per minute
Standard Deviation 9.0
|
64.3 Beats per minute
Standard Deviation 5.6
|
|
Change From Baseline in Heart Rate
Change from Baseline at Day 2
|
5.2 Beats per minute
Standard Deviation 6.3
|
1.8 Beats per minute
Standard Deviation 3.7
|
PRIMARY outcome
Timeframe: Up to Day 8Population: ITT Population
A baseline physical examination was performed at screening. Otherwise, abbreviated physical examinations were conducted and were to include heart, lung, and abdomen. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: Pharmacokinetic (PK) Evaluable Population: all ITT participants who had adequate and reliable PK data for the evaluation of PK of AKB-6548 plasma concentrations.
Plasma samples were collected from the participants at the defined time points. Cmax was defined as the maximum observed plasma concentration. Cmax was calculated using the standard non-compartmental method.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Geometric Mean Maximum Observed Plasma Concentration (Cmax) of AKB-6548
|
42.486 Micrograms per millilitre (mcg/mL)
Geometric Coefficient of Variation 36.314
|
40.952 Micrograms per millilitre (mcg/mL)
Geometric Coefficient of Variation 35.022
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: PK Evaluable Population
Plasma samples were collected from the participants at the defined time points. Tmax was defined as the time to reach maximum plasma concentration. Tmax was calculated using the standard non-compartmental method.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Median Time to Reach Cmax (Tmax) of AKB-6548
|
5.5 Hours
Interval 1.0 to 8.0
|
5.0 Hours
Interval 2.0 to 6.0
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: PK Evaluable Population
Plasma samples were collected from the participants at the defined time points. λz was calculated using linear regression of the terminal linear portion of the log concentration vs. time curve. The parameter was calculated by linear least-squares regression analysis using three or more concentrations, excluding Cmax.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Mean Terminal Elimination Rate Constant (λz)
|
0.105 1/Hour
Standard Deviation 0.029
|
0.086 1/Hour
Standard Deviation 0.020
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: PK Evaluable Population
Plasma samples were collected from the participants at the defined time points. T½ was defined as apparent terminal elimination half-life. T½ was calculated using the standard non-compartmental method.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Median Terminal Elimination Half-life (T½)
|
7.070 Hours
Interval 4.53 to 9.93
|
7.530 Hours
Interval 5.68 to 12.27
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: PK Evaluable Population
Plasma samples were collected from the participants at the defined time points. AUC\[0-T) was defined as the area under the plasma concentration-time curve, from time=0 to the last measurable concentration (Ct) up to 24 hours, calculated by the linear trapezoidal method. AUC\[0-T) was calculated using the standard noncompartmental method.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Geometric Mean Area Under the Plasma Concentration-time Curve From 0 to Time T Over a Dosing Interval (AUC[0-T])
|
441.651 mcg*hr/mL
Geometric Coefficient of Variation 36.162
|
448.399 mcg*hr/mL
Geometric Coefficient of Variation 34.081
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: PK Evaluable Population
Plasma samples were collected from the participants at the defined time points. AUC\[0-∞\] was defined as the area under the plasma concentration-time curve from time=0 and extrapolated to infinity. AUC\[0-∞\] was calculated using the standard non-compartmental method.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Geometric Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-∞])
|
503.688 mcg*hr/mL
Geometric Coefficient of Variation 41.671
|
535.813 mcg*hr/mL
Geometric Coefficient of Variation 40.320
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: PK Evaluable Population
Plasma samples were collected from the participants at the defined time points. CL/F was defined as apparent oral clearance, calculated as Dose/AUC(0-inf). CL/F was calculated using the standard non-compartmental method.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Geometric Mean Apparent Oral Clearance (CL/F)
|
0.995 Litre per Hour (L/hr)
Geometric Coefficient of Variation 41.683
|
0.934 Litre per Hour (L/hr)
Geometric Coefficient of Variation 40.324
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)Population: PK Evaluable Population
Plasma samples were collected from the participants at the defined time points. Vd/F was defined as the apparent volume of distribution during the terminal phase, calculated as Dose/\[λz \* AUC(0-inf)\]. Vd/F was calculated using the standard non-compartmental method.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Geometric Mean Apparent Volume of Distribution During the Terminal Phase (Vd/F)
|
9.863 Liter
Geometric Coefficient of Variation 20.479
|
11.105 Liter
Geometric Coefficient of Variation 31.747
|
SECONDARY outcome
Timeframe: Baseline; 8, 12, and 24 hours post-dosePopulation: ITT Population. Overall number of participants analyzed represents participants with valid EPO measurements at both baseline and the post-dose hour.
The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values.
Outcome measures
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 Participants
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 Participants
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
|---|---|---|
|
Change From Baseline in Mean Erythropoietin (EPO)
Baseline
|
23.14 milli-international units per milliliter
Standard Deviation 15.00
|
21.65 milli-international units per milliliter
Standard Deviation 15.84
|
|
Change From Baseline in Mean Erythropoietin (EPO)
8 Hours Post-dose
|
6.16 milli-international units per milliliter
Standard Deviation 9.97
|
12.07 milli-international units per milliliter
Standard Deviation 11.13
|
|
Change From Baseline in Mean Erythropoietin (EPO)
12 Hours Post-dose
|
5.41 milli-international units per milliliter
Standard Deviation 7.66
|
11.09 milli-international units per milliliter
Standard Deviation 8.71
|
|
Change From Baseline in Mean Erythropoietin (EPO)
24 Hours Post-dose
|
-1.44 milli-international units per milliliter
Standard Deviation 5.71
|
2.08 milli-international units per milliliter
Standard Deviation 5.57
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; 24 hours post-doseOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; 24 hours post-doseOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; 24 hours post-doseOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; 24 hours post -doseOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; 24 hours post -doseOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; 24 hours post-doseOutcome measures
Outcome data not reported
Adverse Events
Cohort 1: CKD Stage 3 Vadadustat
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 2: CKD Stage 4 Vadadustat
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1: CKD Stage 3 Vadadustat
n=10 participants at risk
Participants with CKD Stage 3 with Estimated Glomerular Filtration Rate (eGFR) 30 - 59 mL/minute received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
|
Cohort 2: CKD Stage 4 Vadadustat
n=12 participants at risk
Participants with CKD Stage 4 with eGFR \<30 mL/minute and not yet on dialysis received a single dose of Vadadustat 500 milligrams (mg) (one 200 mg capsule and one 300 mg capsule) orally in fasted condition.
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|---|---|---|
|
Cardiac disorders
Tachycardia
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Gastrointestinal disorders
Nausea
|
20.0%
2/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
General disorders
Catheter Site Inflammation
|
0.00%
0/10 • Up to Day 8
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.
|
8.3%
1/12 • Up to Day 8
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.
|
|
General disorders
Pyrexia
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/10 • Up to Day 8
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.
|
8.3%
1/12 • Up to Day 8
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.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/10 • Up to Day 8
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.
|
8.3%
1/12 • Up to Day 8
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.
|
|
Nervous system disorders
Tremor
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/10 • Up to Day 8
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.
|
8.3%
1/12 • Up to Day 8
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.
|
|
Skin and subcutaneous tissue disorders
Cold Sweat
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
|
Vascular disorders
Hypotension
|
10.0%
1/10 • Up to Day 8
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.
|
0.00%
0/12 • Up to Day 8
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER