NCT04707573

Study to Assess the Safety and Pharmacokinetics of AKB-6548 in Participants With Chronic Kidney Disease (CKD), Stages 3 and 4

Completed Phase 2 Results posted Last updated 28 June 2022

What this trial tests

Phase 2 trial testing Vadadustat in Chronic Kidney Disease in 22 participants. Completed in 24 September 2010.

Timeline

8 July 2010

Primary endpoint
24 September 2010

24 September 2010

Quick facts

Lead sponsor	Akebia Therapeutics
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	22
Start date	8 July 2010
Primary completion	24 September 2010
Estimated completion	24 September 2010
Sites	2 locations across United States

Drugs / interventions tested

• Vadadustat — full drug profile →

Conditions studied

• Chronic Kidney Disease — all drugs for Chronic Kidney Disease →

Sponsor

Akebia Therapeutics — full company profile →

Who can join

Adults 18 to 79, any sex, with Chronic Kidney Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Primary · Up to Day 8

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

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	6
Cohort 2: CKD Stage 4 Vadadustat	2

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values Primary · Up to Day 8

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

Urinalysis

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	0
Cohort 2: CKD Stage 4 Vadadustat	0

Hematology

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	0
Cohort 2: CKD Stage 4 Vadadustat	0

Serum chemistry

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	1
Cohort 2: CKD Stage 4 Vadadustat	0

Coagulation

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	0
Cohort 2: CKD Stage 4 Vadadustat	0

Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values Primary · Up to Day 8

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	2
Cohort 2: CKD Stage 4 Vadadustat	0

Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings Primary · Up to Day 2

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	0
Cohort 2: CKD Stage 4 Vadadustat	0

Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval Primary · Baseline; Day 2

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.

Baseline PR interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	178.8	± 44.2
Cohort 2: CKD Stage 4 Vadadustat	182.5	± 24.2

Change from Baseline at Day 2 PR interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	-12.4	± 28.4
Cohort 2: CKD Stage 4 Vadadustat	-3.5	± 5.5

Baseline QRS interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	98.8	± 20.7
Cohort 2: CKD Stage 4 Vadadustat	97.7	± 26.0

Change from Baseline at Day 2 QRS interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	-0.8	± 3.2
Cohort 2: CKD Stage 4 Vadadustat	0.0	± 5.4

Baseline QT interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	427.2	± 22.0
Cohort 2: CKD Stage 4 Vadadustat	426.5	± 39.7

Change from Baseline at Day 2 QT interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	-13.8	± 21.8
Cohort 2: CKD Stage 4 Vadadustat	-2.3	± 16.7

Baseline QTc interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	423.5	± 22.8
Cohort 2: CKD Stage 4 Vadadustat	439.5	± 35.8

Change from Baseline at Day 2 QTc interval

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	3.1	± 10.2
Cohort 2: CKD Stage 4 Vadadustat	2.0	± 18.2

Change From Baseline in Heart Rate Primary · Baseline; Day 2

The heart rate evaluation was performed after the participant had been resting comfortably in a supine position for approximately 10 minutes.

Baseline

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	59.8	± 9.0
Cohort 2: CKD Stage 4 Vadadustat	64.3	± 5.6

Change from Baseline at Day 2

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	5.2	± 6.3
Cohort 2: CKD Stage 4 Vadadustat	1.8	± 3.7

Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings Primary · Up to Day 8

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	0
Cohort 2: CKD Stage 4 Vadadustat	0

Geometric Mean Maximum Observed Plasma Concentration (Cmax) of AKB-6548 Primary · Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	42.486	± 36.314
Cohort 2: CKD Stage 4 Vadadustat	40.952	± 35.022

Median Time to Reach Cmax (Tmax) of AKB-6548 Primary · Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	5.5	1.0 – 8.0
Cohort 2: CKD Stage 4 Vadadustat	5.0	2.0 – 6.0

Mean Terminal Elimination Rate Constant (λz) Primary · Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	0.105	± 0.029
Cohort 2: CKD Stage 4 Vadadustat	0.086	± 0.020

Median Terminal Elimination Half-life (T½) Primary · Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	7.070	4.530 – 9.930
Cohort 2: CKD Stage 4 Vadadustat	7.530	5.680 – 12.270

Geometric Mean Area Under the Plasma Concentration-time Curve From 0 to Time T Over a Dosing Interval (AUC[0-T]) Primary · Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)

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.

Group	Value	95% CI
Cohort 1: CKD Stage 3 Vadadustat	441.651	± 36.162
Cohort 2: CKD Stage 4 Vadadustat	448.399	± 34.081

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 8. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: CKD Stage 3 Vadadustat

Serious: 0/10 (0%)

Deaths: 0/10

Cohort 2: CKD Stage 4 Vadadustat

Serious: 0/12 (0%)

Deaths: 0/12

Other adverse events (17 terms — click to expand)

Reaction	System	Cohort 1: CKD Stage 3 Vada…	Cohort 2: CKD Stage 4 Vada…
Nausea	Gastrointestinal disorders	—	—
Tachycardia	Cardiac disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Catheter Site Inflammation	General disorders	—	—
Pyrexia	General disorders	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Pain in Extremity	Musculoskeletal and connective tissue disorders	—	—
Skin Papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Headache	Nervous system disorders	—	—
Somnolence	Nervous system disorders	—	—
Tremor	Nervous system disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Cold Sweat	Skin and subcutaneous tissue disorders	—	—
Hypotension	Vascular disorders	—	—

Data from ClinicalTrials.gov NCT04707573 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.