Clinical trial NCT03680352: Pharmacokinetics of Cefepime and AAI101 in Subjects With Renal Insufficiency and Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: PK in Patients With Various Degrees of Renal Impairment
Lead sponsor: Allecra
Sponsor class: INDUSTRY
First posted: 2018-09-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The maximum plasma concentration (Cmax) of cefepime and AAI101
timeFrame: Up to 48 hours post-dose
measure: AUC0-inf: area under the concentration-time curve (AUC) from time 0 extrapolated to infinity of cefepime and AAI101
timeFrame: Up to 48 hours post-dose
Secondary outcomes:
measure: The number of volunteers with adverse events as a measure of safety and tolerability
timeFrame: Up to 96 hours post-dose
Other outcomes:
Locations:
city: Praha
country: Czechia
facility: Pharmaceutical Research Associates CZ, s.r.o.
state: Jankovcova
city: Budapest
country: Hungary
facility: PRA Magyarország Kft Fázis I-es Klinikai Farmakológiai Vizsgálóhely
state: Rottenbiller Utca 13
Study officials:
References: