Safety, Tolerability, and Pharmacokinetics of KBP-5074 Following Oral Administration in Chronic Kidney Disease

Inclusion Criteria

• Male or female, between 18 and 75 years of age, inclusive.
• Body mass index (BMI) between 19 and 42 kg/m2, inclusive.
• Has severe CKD, defined as eGFR ≥15 mL/min/1.73 m2 and ≤29 mL/min/1.73 m2 based on the IDMS traceable15 MDRD equation, according to laboratory results at Screening (non-HD patients only [Part 1]). Patients with a prior history of greater than 2 weeks of dialysis in the past and who have dialyzed in the 6 months prior to dosing on Day 1 will be excluded. Patients who have had temporary dialysis for acute kidney injury will be allowed at the discretion of the Investigator.
• Serum potassium between 3.3 and 4.8 mmol/L, inclusive, at both Screening and Check-in (Day -1) (non-HD patients only [Part 1]). One repeat test will be allowed to exclude lab error or hemolyzed samples.
• Is on a hemodialysis schedule for at least 45 days with KT/V ≥1.2 for end-stage renal disease (ESRD) regardless of the etiology including diabetes, with an average 3 hemodialysis sessions per week (HD patients only [Part 2]).
• Is a nonsmoker or light smoker (smokes fewer than 10 cigarettes per day). Alcohol addressed in exclusion.
• Female patients cannot be pregnant or lactating/breast-feeding and will either be postmenopausal (female patients who state they are postmenopausal should have had cessation of menses for >1 year and have serum follicle stimulating hormone [FSH] levels >40 mIU/mL and estradiol 5.5 mmol/L during the 2 weeks prior to the Screening visit.
• History of stroke within 3 months prior to the dose of study drug on Day 1.
• History of cardiac transplant.
• History of severe uncontrolled arrhythmia, acute myocardial infarction, or acute coronary syndrome within 3 months prior to the dose of study drug on Day 1.
• Clinical diagnosis of heart failure and persistent symptoms (New York Heart Association Class II to IV) at either the Screening visit or at Check-in (Day 1).
• History of stomach or intestinal surgery (except that cholecystectomy, appendectomy, and/or hernia repair will be allowed).
• History of prescription drug abuse, illicit drug use, or alcohol abuse according to medical history within 6 months prior to the Screening visit or any alcohol use or for at least 48 hours prior to dosing on Day 1.
• History of clinically significant acute or chronic hepatitis (including infectious, metabolic, autoimmune, genetic, ischemic, or other forms), hepatocirrhosis, or hepatic tumors.
• Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C (HCV) antibody. If a patient with Severe renal impairment or on HD has positive test results for HCV antibody but liver function tests are otherwise not CS, the patient may be included at the Investigator's discretion.
• Clinically significant abnormal liver function test at screening or Check-in (Day -1), defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN) or total bilirubin >ULN.
• Recent (within 3 month prior to the dose of study drug on Day 1) or planned coronary revascularization by angioplasty or cardiovascular surgery (excluding HD vascular access).
• Kidney transplant scheduled within the year.
• Systolic blood pressure 200 mmHg and/or diastolic blood pressure 110 mmHg during the Screening visit and before the dose of study drug on Day 1; may be repeated at the discretion of the Investigator.
• Positive screen for alcohol or drugs of abuse (except for patients with a positive drug screen test if it is a result of a prescribed medication from their physician) at Screening and Check-in (Day -1). Hemodialysis patients will be tested with serum drug screen at Screening and using salivary testing at Check-in (Day -1).
• Female is pregnant or breastfeeding within 2 years prior to the dose of study drug on Day 1 or positive pregnancy test (serum/urine) result during the Screening visit and before the dose of s