Overview

This trial is active, not recruiting.

Conditions healthy, renal insufficiency
Treatment kbp-5074
Phase phase 1/phase 2
Sponsor KBP Biosciences
Start date July 2015
End date September 2016
Trial size 26 participants
Trial identifier NCT02653014, KBP5074-1-002

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Healthy Volunteers will receive multiple dose of KBP-5074
kbp-5074
Drug Intervention
(Experimental)
Healthy Volunteers will receive multiple dose of KBP-5074
kbp-5074
Drug Intervention
(Experimental)
Healthy Volunteers will receive multiple dose of KBP-5074
kbp-5074
Drug Intervention
(Experimental)
Healthy Volunteers will receive multiple dose of KBP-5074
kbp-5074
Drug Intervention
(Experimental)
Subjects with mild to moderate renal impairment will receive multiple dose of KBP-5074
kbp-5074
Drug Intervention
(Experimental)
Subjects with mild to moderate renal impairment will receive multiple dose of KBP-5074
kbp-5074
Drug Intervention

Primary Outcomes

Measure
Safety and tolerability (i.e., number of participants with adverse events, abnormal vital signs, clinical laboratory findings, 12-lead ECGs and physical examinations) in healthy subjects
time frame: Up to 27 days
Safety and tolerability (i.e., number of participants with adverse events, abnormal vital signs, clinical laboratory findings, 12-lead ECGs and physical examinations) in subjects with mild to moderate renal impairment
time frame: Up to 69 days

Secondary Outcomes

Measure
Area Under Curve (AUC) in healthy subjects
time frame: 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
Area Under Curve (AUC) in subjects with mild to moderate renal impairment
time frame: 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
The effect of mild to moderate renal impairment on the Area Under Curve (AUC)
time frame: Up to 15 days
Plasma aldosterone levels in healthy subjects
time frame: 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 levels in healthy subjects
time frame: 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 levels in subjects with mild to moderate renal impairment
time frame: 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 levels in subjects with mild to moderate renal impairment
time frame: 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
Urinary Albumin to Creatinine Ratio (UACR) in subjects with mild to moderate renal impairment
time frame: 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
Blood Pressure in subjects with mild to moderate renal impairment
time frame: 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

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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).

Additional Information

Official title An Open-Label, Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability and Pharmacokinetics of KBP-5074 in Healthy Subjects With a Separate Panel in Subjects With Mild to Moderate Renal Impairment
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by KBP Biosciences.