Pharmacokinetics of Cefepime and AAI101 in Subjects With Renal Insufficiency and Healthy Subjects

Study Overview
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Brief Summary
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This is a Phase 1, multi-center, open-label, PK and safety study of a single dose of AAI101 in combination with cefepime in male and female subjects with mild renal impairment (Group 1, n = 6), moderate renal impairment (Group 2, n = 6), severe renal impairment (Group 3, n = 6), ESRD requiring dialysis (Group 4, n = 6), and normal renal function (Group 5, n = 6) as defined using the estimated value for creatinine clearance (CLcr) at Screening. The study consists of a 28-day screening period, followed by a single dose administration of AAI101 in combination with cefepime antibiotic on Day 1, an in house period (assessment period) and follow-up visit. All subjects will be confined to the study site from Day -1 (the day before dosing) until the morning of Day 3. The follow-up visits will occur on Day 7 (±2 days), on Day 14 (±2 days), and on Day 30 (±2 days), if the results of the safety hepatic assessments are abnormal on Day 14 (±2 days). Group 4 (ESRD requiring dialysis) will have 2 in-house periods (separated by at least 7 days), and will receive the single doses of AAI101 in combination with cefepime antibiotic once after dialysis and once before dialysis. The follow-up visit for Group 4 will occur on Day 7 (±2 days), on Day 14 (±2 days), and on Day 30 (±2 days), if the results of the safety hepatic assessments are abnormal on Day 14 (±2 days), counting from Day 1 of the second period.

Official Title
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Phase 1, Open-label, Parallel Group, Single-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of AAI101 With Cefepime in Subjects With Varying Degrees of Renal Function

Conditions
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PK in Patients With Various Degrees of Renal Impairment

Intervention / Treatment
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* Drug: cefepime/AAI101


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria Adult male or female subjects age 18 to 70 years, inclusive BMI 18.0 35.0 kg/m2, inclusive, where BMI (kg/m2) = body weight (kg) / height2 (m2) Subjects with Renal Impairment (in addition) Stable renal impairment, defined as no clinically significant change in disease status, as judged by the Investigator Healthy Subjects (in addition) Subjects with normal renal function as evidenced by CLcr Judged to be in good health in the opinion of the Investigator on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality OR Subject has a stable disease (e.g., hypertension, hyperlipidemia, diabetes mellitus, hyperthyreosis) under medical control.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Other
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cefepime/AAI101 combination<br>Investigational drug | Drug: cefepime/AAI101<br>* Fixed dose combination of cefepime and AAI101<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum plasma concentration (Cmax) of cefepime and AAI101 | Cmax will be compared before and after administration of a single dose of cefepime/AAI101 | Up to 48 hours post-dose | 
| AUC0-inf: area under the concentration-time curve (AUC) from time 0 extrapolated to infinity of cefepime and AAI101 | AUC0-inf will be compared before and after administration of a single dose of cefepime/AAI101 | Up to 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of volunteers with adverse events as a measure of safety and tolerability | Assessments will be made via recording of AEs. | Up to 96 hours post-dose |