Safety, Tolerability and Pharmacokinetics of KBP-5074 in Healthy Subjects and Subjects With Renal Impairment
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 Healthy Volunteers will receive multiple dose of KBP-5074 |
Drug: KBP-5074
Other Names:
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| Experimental: Cohort 2 Healthy Volunteers will receive multiple dose of KBP-5074 |
Drug: KBP-5074
Other Names:
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| Experimental: Cohort 3 Healthy Volunteers will receive multiple dose of KBP-5074 |
Drug: KBP-5074
Other Names:
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| Experimental: Cohort 4 Healthy Volunteers will receive multiple dose of KBP-5074 |
Drug: KBP-5074
Other Names:
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| Experimental: Cohort 5 Subjects with mild to moderate renal impairment will receive multiple dose of KBP-5074 |
Drug: KBP-5074
Other Names:
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| Experimental: Cohort 6 Subjects with mild to moderate renal impairment will receive multiple dose of KBP-5074 |
Drug: KBP-5074
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Safety and tolerability [Up to 69 days]
Rate of adverse events
Secondary Outcome Measures
- 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
- 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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria for Part 1:
-
Healthy male or female subject
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Are between the ages of 18 and 45 years (inclusive);
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Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight not less than 50 kg.
Exclusion Criteria for Part 1:
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Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity;
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Known or suspected malignancy;
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Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody;
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Positive pregnancy test result.
Inclusion Criteria for Part 2:
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Are between the ages of 18 and 75 years (inclusive);
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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;
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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);
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Subjects treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)
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Serum potassium≥3.3 mmol/L and ≤4.8 mmol/L;
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Body mass index (BMI) of 19 to 40 kg/m2 inclusive and body weight not less than 50 kg.
Exclusion Criteria for Part 2:
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Severe uncontrolled hypertension (diastolic > 115 mmHg or systolic blood pressure > 180 mmHg) at either the Screening visit or the Study Check-in Visit;
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Type I diabetes mellitus or poorly controlled Type 2 diabetes mellitus (HbA1c > 10%) at the Screening visit;
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Prior kidney transplant, or anticipated need for transplant during study participation;
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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;
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Known or suspected contraindications to study medications, including history of hypersensitivity or allergy to ACE inhibitors, ARBs, or aldosterone antagonists;
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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;
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Diabetic gastroparesis;
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Known bilateral clinically relevant renal artery stenosis (>75% reduction in artery diameter).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research by Design, LLC | Evergreen Park | Illinois | United States | 60805 |
Sponsors and Collaborators
- KBP Biosciences
Investigators
- Study Chair: Fred Yang, PhD, KBP Biosciences USA Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KBP5074-1-002