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

NCT02653014 | Completed Phase 1 FDA Drug

• 1 other identifier: KBP5074-1-002
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Renal Insufficiency

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  Rate of adverse events

  Up to 69 days

Secondary Outcomes (9)

• 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

• 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

• The effect of mild to moderate renal impairment on the Area Under Curve (AUC)

  Up to 15 days

• 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

• 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

Study Arms (4)

Cohort 1

EXPERIMENTAL

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

Drug: KBP-5074

Cohort 2

EXPERIMENTAL

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

Drug: KBP-5074

Cohort 3

EXPERIMENTAL

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

Drug: KBP-5074

Cohort 4

EXPERIMENTAL

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

Drug: KBP-5074

Interventions

KBP-5074 DRUG

Also known as: mineralocorticoid receptor antagonist

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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;

Sponsors & Collaborators

• KBP Biosciences: lead

Study Sites (1)

Research by Design, LLC

Evergreen Park, Illinois, 60805, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

KBP-5074; Mineralocorticoid Receptor Antagonists

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2015
• First Posted: January 12, 2016
• Study Start: July 29, 2015
• Primary Completion: May 26, 2016
• Study Completion: March 28, 2017
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)