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

KBP Biosciences

Status and phase: Completed; Phase 1

Conditions: Healthy; Renal Insufficiency

Treatments: Drug: KBP-5074

Study type: Interventional

Funder types: Industry

Identifiers

NCT02653014

KBP5074-1-002

Details and patient eligibility

About

This multiple ascending dose (MAD) study in healthy subjects and subjects with mild to moderate renal impairment will evaluate the safety, tolerability and pharmacokinetics of KBP-5074. Safety/tolerability data and Pharmacokinetics (PK)/Pharmacodynamics (PD) (plasma aldosterone, serum potassium, UACR and Blood Pressure) relationships will be explored to support the selection of dosing regimens of KBP-5074 that are suitable for the Phase II/III study.

Full description

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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 4 patient groups

Cohort 1

Experimental group

Description:

Healthy Volunteers will receive 2.5mg of KBP-5074, QD, 14 days

Treatment:

Drug: KBP-5074

Cohort 2

Experimental group

Description:

Healthy Volunteers will receive 5.0mg of KBP-5074, QD, 14 days

Treatment:

Drug: KBP-5074

Cohort 3

Experimental group

Description:

Subjects with mild to moderate renal impairment will receive 0.5mg of KBP-5074, QD, 56 days

Treatment:

Drug: KBP-5074

Cohort 4

Experimental group

Description:

Subjects with mild to moderate renal impairment will receive 2.5mg of KBP-5074, QD, 56 days

Treatment:

Drug: KBP-5074