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

NCT03680352 | Completed Phase 1 FDA Drug

• 1 other identifier: AT-102
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

PK in Patients With Various Degrees of Renal Impairment

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• The number of volunteers with adverse events as a measure of safety and tolerability

  Up to 96 hours post-dose

Study Arms (1)

cefepime/AAI101 combination

EXPERIMENTAL

Investigational drug

Drug: cefepime/AAI101

Interventions

cefepime/AAI101 DRUG

Fixed dose combination of cefepime and AAI101

cefepime/AAI101 combination

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Allecra: lead

Study Sites (2)

Pharmaceutical Research Associates CZ, s.r.o.

Prague, Jankovcova, 170 00, Czechia

Location

PRA Magyarország Kft Fázis I-es Klinikai Farmakológiai Vizsgálóhely

Budapest, Rottenbiller Utca 13, HJ-1077, Hungary

Location

MeSH Terms

Interventions

Cefepime; enmetazobactam

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: September 21, 2018
• Study Start: September 1, 2017
• Primary Completion: December 1, 2018
• Study Completion: December 30, 2018
• Last Updated: June 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); CZ (1)