Safety, Tolerability and Pharmacokinetics of KBP-5074 in Healthy Subjects and Subjects With Renal Impairment

This study consists of two parts: Part 1 is an open-label, multiple ascending dose (MAD)
study to evaluate the safety, tolerability and pharmacokinetics of KBP-5074 in healthy
subjects. The safety and tolerability will be assessed at each dose level before progressing
to the next higher dose. Part 2 is an open label, randomized, parallel study to assess the
safety and tolerability, the effect of renal dysfunction on the pharmacokinetics of KBP-5074,
as well as the PK/PD relationship in subjects with mild to moderate renal impairment.

Inclusion Criteria for Part 1:

- Healthy male or female subject

- Are between the ages of 18 and 45 years (inclusive);

- Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight not less than 50 kg.

Exclusion Criteria for Part 1:

- Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal,
endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic,
immunologic, lipid metabolism disorders, or drug hypersensitivity;

- Known or suspected malignancy;

- Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), or hepatitis C (HCV) antibody;

- Positive pregnancy test result.

Inclusion Criteria for Part 2:

- Are between the ages of 18 and 75 years (inclusive);

- Mild to moderate chronic kidney disease (defined as estimated glomerular filtration
rate (eGFR) > 30 and ≤89 mL/min/1.73 m2, using the modification of diet in renal
disease (MDRD) formula, for > 3 months;

- Proteinuria (defined as urine albumin to creatinine ratio (UACR) ≥100 mg/g and ≤3,000
mg/g in two mid-morning urine specimens within a month interval);

- Subjects treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin
receptor blocker (ARB)

- Serum potassium≥3.3 mmol/L and ≤4.8 mmol/L;

- Body mass index (BMI) of 19 to 40 kg/m2 inclusive and body weight not less than 50 kg.

Exclusion Criteria for Part 2:

- Severe uncontrolled hypertension (diastolic > 115 mmHg or systolic blood pressure >
180 mmHg) at either the Screening visit or the Study Check-in Visit;

- Type I diabetes mellitus or poorly controlled Type 2 diabetes mellitus (HbA1c > 10%)
at the Screening visit;

- Prior kidney transplant, or anticipated need for transplant during study
participation;

- Clinical diagnosis of heart failure and persistent symptoms (New York Heart
Association [NYHA] Class II- IV) at either the Screening visit or the Study Check-in
Visit;

- Known or suspected contraindications to study medications, including history of
hypersensitivity or allergy to ACE inhibitors, ARBs, or aldosterone antagonists;

- Any clinically significant disorder, except for conditions associated with type 2
diabetes mellitus history, which in the investigators opinion could interfere with the
results of the trial;

- Diabetic gastroparesis;

- Known bilateral clinically relevant renal artery stenosis (>75% reduction in artery
diameter).