Phase 1 Single Ascending Dose Study to Evaluate Safety, Tolerability and Pharmacokinetics of KBP-5074

An Open-Label, Parallel-Group, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability and Pharmacokinetics of KBP-5074 Following Oral Administration and With a Food Effect Panel

This single ascending dose (SAD) study in healthy subjects will evaluate the safety, tolerability and pharmacokinetics of KBP-5074. PK/PD (plasma aldosterone, serum potassium and urine albumin levels) relationships will be explored to support the selection of dosing regimens of KBP-5074 that are suitable for the Phase 2 dose-finding study to evaluate the efficacy, safety and tolerability of KBP-5074 in patients that could slow the progression of nephropathy as well as control hypertension.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: KBP-5074

Detailed Description

This is an open-label, parallel-group, dose-escalation study to evaluate the safety, tolerability and pharmacokinetics of KBP-5074 following a single dose administration of KBP-5074 with and without food. The study includes 2 parts.

Part 1: Pharmacokinetics from each dose cohort will be characterized before initiation of dosing in the subsequent cohorts. Eight subjects in each dose cohort will receive active drug. The total number of cohorts will be up to 5. Extensive PK samplings will be collected prior to and following administration of single dose of KBP-5074.

Part 2: A separate panel of 6 subjects will receive a single dose of KBP-5074 under fed conditions. Extensive PK samplings will be collected prior to and following administration of single dose of KBP-5074 under fed conditions.

Serum and plasma samples for pharmacodynamic markers (plasma aldosterone and serum potassium levels) will be collected at pre-dose and postdose in both Part 1 and Part 2.

The urine samples will be also used for quantitative determination of urinary albumin in both Part 1 and Part 2.

Safety assessments will include monitoring of adverse events (AEs), vital signs (blood pressure, pulse rate, respiratory rate and oral temperature), clinical laboratory findings, 12-lead electrocardiograms (ECGs), and physical examination findings.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index (BMI) 19 ≤ BMI ≤ 30 kg/m2, no significant medical history, normal renal function and in good general health

Exclusion Criteria:

• Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity; A history of prescription drug abuse, or illicit drug use within 6 months prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KBP-5074: Cohort 1; Healthy Volunteers will receive one dose of KBP-5074	Drug: KBP-5074; Comparisons of different doses of study drug
Experimental: KBP-5074: Cohort 2; Healthy Volunteers will receive one dose of KBP-5074	Drug: KBP-5074; Comparisons of different doses of study drug
Experimental: KBP-5074: Cohort 3; Healthy Volunteers will receive one dose of KBP-5074	Drug: KBP-5074; Comparisons of different doses of study drug
Experimental: KBP-5074: Cohort 4; Healthy Volunteers will receive one dose of KBP-5074	Drug: KBP-5074; Comparisons of different doses of study drug
Experimental: KBP-5074: Cohort 5; Healthy Volunteers will receive one dose of KBP-5074	Drug: KBP-5074; Comparisons of different doses of study drug
Experimental: KBP-5074: Fed Group; Healthy Volunteers will receive one dose of KBP-5074	Drug: KBP-5074; Comparisons of different doses of study drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety and tolerability	Assessing the number of participants with adverse events, abnormal vital signs, clinical laboratory findings, 12-lead ECGs and physical examinations): pre dose and post dose	14 days
Area Under Curve (AUC) Time Frame	Assessing drug exposure across time. AUC is a useful metric when trying to determine whether two formulations of the same dose (for example a capsule and a tablet) result in equal amounts of tissue or plasma exposure. Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 168, 216, 264 and 312 hours post-dose	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of food on Area Under Curve (AUC) Time Frame	Assessing the food effect on drug exposure across time at pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 168, 216, 264 and 312 hours post-dose	14 days
The plasma aldosterone, serum potassium and urine albumin levels	Assessing blood levels of aldosterone, potassium and urine albumin at pre dose and postdose	14 days

Collaborators and Investigators

• Sponsor: KBP Biosciences

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: August 25, 2014
• First Submitted That Met QC Criteria: August 27, 2014
• First Posted (Estimated): August 29, 2014

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: KBP5074-1-001