Clinical trial NCT04707573: Study to Assess the Safety and Pharmacokinetics of AKB-6548 in Participants With Chronic Kidney Disease (CKD), Stages 3 and 4
Official title: A Phase 2A Single Dose, Open Label Study to Assess the Safety and Pharmacokinetics of AKB-6548 in Subjects With Chronic Kidney Disease (CKD), Stages 3 and 4
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Keywords: CKD
CKD, Stage 3
CKD, Stage 4
Vadadustat
pharmacokinetics
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-01-13
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 18 to 79 years of age, inclusive
* Chronic Kidney Disease Stage 3 (Estimated Glomerular Filtration Rate \[eGFR\] 30 to 59 milliliters \[mL\]/minute) or Stage 4 participants (eGFR of \<30 mL/minute that were not yet on dialysis). eGFR was calculated using the Modification of Diet in Renal Disease (MDRD).
* Hemoglobin (Hb) \<13.5 grams per deciliter (g/dL) except for Polycystic Kidney Disease (PKD) participants, in which Hb was to be ≤14 g/dL
* Transferrin saturation (TSAT) \>12% and complete blood count (CBC) indicating normocytic red blood cell morphology, unless the medical monitor and investigator agreed that the participant was appropriate for this study
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.8 x upper limit of normal (ULN)
* Alkaline phosphatase ≤2 x ULN
* Bilirubin ≤1.5 x ULN
* Female participants were not pregnant or breastfeeding. Women of childbearing potential agreed to use an acceptable method of contraception.
* Non-vasectomized male participants agreed to use an acceptable method of contraception
* Understood the procedures and requirements of the study and provided written informed consent and authorization for protected health information disclosure

Exclusion Criteria:

* Any medical or psychological condition that in the opinion of the Investigator would have interfered with the participant's ability to provide informed consent or comply with study instructions
* Any clinically significant or uncontrolled medical condition that in the opinion of the Investigator would have placed the participant at undo risk or would have compromised the interpretability of the findings in this study
* A body mass index (BMI) of greater than 40
* Seropositive for human immunodeficiency virus (HIV) or Hepatitis B surface antigen
* Seropositive for Hepatitis C virus (HCV) antibodies unless ALT, AST, bilirubin tests were within normal limits
* History of chronic liver disease
* Uncontrolled hypertension (diastolic blood pressure \[BP\] \> 110 millimeters of mercury \[mm Hg\] or systolic BP \>190 mm Hg at screening)
* New York Heart Association Class III or IV congestive heart failure
* Myocardial infarction, acute coronary syndrome, or stroke within 6 months of dosing
* History of myelodysplastic syndrome
* Participants known to have diabetic gastroparesis that was either symptomatic on therapy or was refractory to therapy
* Any history of malignancy in the previous 5 years except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or resected benign colonic polyps
* Evidence of active infection unless the medical monitor and investigator agreed that the participant was appropriate for this study
* History of rheumatoid arthritis or systemic lupus erythematosus (SLE) (History of osteoarthritis or gout did not exclude participants from eligibility in the study.)
* Age-related macular degeneration (AMD), diabetic macular edema or active diabetic proliferative retinopathy that was likely to require treatment during the trial
* History of deep vein thrombosis (DVT) that required active treatment. Superficial thrombosis was not excluded.
* History of ongoing hemolysis or diagnosis of hemolytic syndrome
* Known history of bone marrow fibrosis
* History of hemosiderosis or hemochromatosis
* Androgen therapy within 21 days from the last injection
* Red blood cell transfusion within 12 weeks
* Therapy with an erythropoiesis stimulating agent (ESA) such as human recombinant erythropoietin within the past 21 days
* Intravenous iron supplementation within the past 21 days
* Currently taking acetaminophen \> 2.6 grams/day
* History of prior organ transplantation, or stem cell or bone marrow transplantation
* Alcohol consumption greater than 14 or more drinks per week within the past year (1 drink = 12 ounce \[oz\] beer, 5 oz wine, or 1.5 oz hard liquor.)
* Use of an investigational medication or participation in an investigational study within 30 days, or 5 half-lives of the investigational product, whichever was longer, preceding Day 1
* Positive urine toxicology screen for a substance of abuse that had not been prescribed for the participant

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Day 8
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
timeFrame: Up to Day 8
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
timeFrame: Up to Day 8
measure: Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
timeFrame: Up to Day 2
measure: Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
timeFrame: Baseline; Day 2
measure: Change From Baseline in Heart Rate
timeFrame: Baseline; Day 2
measure: Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
timeFrame: Up to Day 8
measure: Geometric Mean Maximum Observed Plasma Concentration (Cmax) of AKB-6548
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
measure: Median Time to Reach Cmax (Tmax) of AKB-6548
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
measure: Mean Terminal Elimination Rate Constant (λz)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
measure: Median Terminal Elimination Half-life (T½)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
measure: Geometric Mean Area Under the Plasma Concentration-time Curve From 0 to Time T Over a Dosing Interval (AUC[0-T])
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
measure: Geometric Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-∞])
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
measure: Geometric Mean Apparent Oral Clearance (CL/F)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
measure: Geometric Mean Apparent Volume of Distribution During the Terminal Phase (Vd/F)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose (Day 2)
Secondary outcomes:
measure: Change From Baseline in Mean Erythropoietin (EPO)
timeFrame: Baseline; 8, 12, and 24 hours post-dose
Other outcomes:
measure: Exploratory: Change From Baseline in Hepcidin at 24 Hours
timeFrame: Baseline; 24 hours post-dose
measure: Exploratory: Change From Baseline in Vascular Endothelial Growth Factor (VEGF) at 24 Hours
timeFrame: Baseline; 24 hours post-dose
measure: Exploratory: Change From Baseline in Transferrin at 24 Hours
timeFrame: Baseline; 24 hours post-dose
measure: Exploratory: Change From Baseline in Cystatin-C at 24 Hours
timeFrame: Baseline; 24 hours post -dose
measure: Exploratory: Change From Baseline in Adiponectin at 24 Hours
timeFrame: Baseline; 24 hours post -dose
measure: Exploratory: Change From Baseline in Ferritin at 24 Hours
timeFrame: Baseline; 24 hours post-dose
Locations:
city: Saint Paul
country: United States
facility: Research Site
state: Minnesota
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
Study officials:
affiliation: Akebia Therapeutics Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: