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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02653014
• Other study ID #: KBP5074-1-002
• Status: Completed
• Phase: Phase 1
• Start date: July 29, 2015
• Est. completion date: March 28, 2017

Study information

• Verified date: August 2018
• Source: KBP Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 28, 2017
• Est. primary completion date: May 26, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy
• Renal Insufficiency

Intervention

Drug:
• KBP-5074

Locations

Country	Name	City	State
United States	Research by Design, LLC	Evergreen Park	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
KBP Biosciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	Rate of adverse events	Up to 69 days
Secondary	Area Under Curve (AUC) in healthy subjects	AUC 0-24 hours	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
Secondary	Area Under Curve (AUC) in subjects with mild to moderate renal impairment	AUC 0-24 hours	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
Secondary	The effect of mild to moderate renal impairment on the Area Under Curve (AUC)	AUC 0-24 hours	Up to 15 days
Secondary	Plasma aldosterone levels in healthy subjects	Plasma aldosterone level	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
Secondary	Serum potassium levels in healthy subjects	Serum potassium level	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
Secondary	Plasma aldosterone levels in subjects with mild to moderate renal impairment	Plasma aldosterone level	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
Secondary	Serum potassium levels in subjects with mild to moderate renal impairment	Serum potassium level	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
Secondary	Urinary Albumin to Creatinine Ratio (UACR) in subjects with mild to moderate renal impairment	Ratio of urinary albumin level to creatinine level	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
Secondary	Blood Pressure in subjects with mild to moderate renal impairment	Systolic and diastolic seated blood pressure	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