This study was conducted to assess the pharmacokinetic (PK) profile, safety, and tolerability in participants with Stage 3 and 4 Chronic Kidney Disease (CKD) following a single oral dose of Vadadustat.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
22
oral capsules
Research Site
Saint Paul, Minnesota, United States
Research Site
Knoxville, Tennessee, United States
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: Up to Day 8
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
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 Day 8
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
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.
Time frame: Up to Day 8
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance.
Time frame: Up to Day 2
Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
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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.
Time frame: Baseline; Day 2
Change From Baseline in Heart Rate
The heart rate evaluation was performed after the participant had been resting comfortably in a supine position for approximately 10 minutes.
Time frame: Baseline; Day 2
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
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.
Time frame: Up to Day 8
Geometric Mean Maximum Observed Plasma Concentration (Cmax) of AKB-6548
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Median Time to Reach Cmax (Tmax) of AKB-6548
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Mean Terminal Elimination Rate Constant (λz)
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Median Terminal Elimination Half-life (T½)
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Geometric Mean Area Under the Plasma Concentration-time Curve From 0 to Time T Over a Dosing Interval (AUC[0-T])
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Geometric Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-∞])
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Geometric Mean Apparent Oral Clearance (CL/F)
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Geometric Mean Apparent Volume of Distribution During the Terminal Phase (Vd/F)
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Change From Baseline in Mean Erythropoietin (EPO)
The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values.
Time frame: Baseline; 8, 12, and 24 hours post-dose