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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: KBP-5074


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability (i.e., number of participatns with adverse events, abnormal vital signs, clinical laboratory findings, 12-lead ECGs and physical examinations): predose and postdose |  | 14 days | 
| Area Under Curve (AUC) Time Frame: 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: 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 | 
| The plasma aldosterone, serum potassium and urine albumin levels: predose and postdose |  | 14 days |