Healthy, Renal Insufficiency
Conditions
Brief summary
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.
Detailed 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.
Interventions
DRUGKBP-5074
Sponsors
KBP Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | Up to 69 days | Rate of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve (AUC) in subjects with mild to moderate renal impairment | pre-dose and 2, 4, 6, 8, 10, 12, 18, and 24 hours post dose on Day 1; pre-dose on Days 8, 11, 12, and 13; pre-dose and 2, 4, 6, 8, 10, 12, 18, and 24 hours post dose on Day 14; pre-dose on Days 29 and 43; and pre-dose and 6, 12, and 24 hours on Day 56 | AUC 0-24 hours |
| The effect of mild to moderate renal impairment on the Area Under Curve (AUC) | Up to 15 days | AUC 0-24 hours |
| Plasma aldosterone levels in healthy subjects | Pre-dose, 6, and 24 hours post dose on Day 1; pre-dose on Day 8; and 24 hours post last dose on Day 15 | Plasma aldosterone level |
| Serum potassium levels in healthy subjects | Pre-dose, 6, and 24 hours post dose on Day 1; pre-dose on Day 8; and 24 hours post last dose on Day 15 | Serum potassium level |
| Area Under Curve (AUC) in healthy subjects | pre-dose and 2, 4, 6, 8, 10, 12, 18, and 24 hours post dose on Day 1; pre-dose on Days 8, 11, 12, and 13; and pre-dose and 2, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 168, 216, 264, and 312 hours post dose on Day 14 | AUC 0-24 hours |
| Serum potassium levels in subjects with mild to moderate renal impairment | Pre-dose, 6, and 24 hours post dose on Day 1; pre-dose on Days 8, 15, 29, and 43; and 24 hours post last dose on Day 57 | Serum potassium level |
| Urinary Albumin to Creatinine Ratio (UACR) in subjects with mild to moderate renal impairment | Pre-dose, 6, and 24 hours post dose on Day 1; pre-dose on Days 8, 15, 29, and 43; and 24 hours post last dose on Day 57 | Ratio of urinary albumin level to creatinine level |
| Blood Pressure in subjects with mild to moderate renal impairment | Pre-dose, 6, and 24 hours post dose on Day 1; pre-dose on Days 8, 15, 29, and 43; and 24 hours post last dose on Day 57 | Systolic and diastolic seated blood pressure |
| Plasma aldosterone levels in subjects with mild to moderate renal impairment | Pre-dose, 6, and 24 hours post dose on Day 1; pre-dose on Days 8, 15, 29, and 43; and 24 hours post last dose on Day 57 | Plasma aldosterone level |
Countries
United States
Outcome results
None listed