Study to Assess the Safety and Pharmacokinetics of AKB-6548 in Participants With Chronic Kidney Disease (CKD), Stages 3 and 4
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Vadadustat
Intervention description: oral capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: CKD; CKD, Stage 3; CKD, Stage 4; Vadadustat; pharmacokinetics

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