Impact of Obesity on the Pharmacokinetics of Imipenem-Relebactam in ICU Patients

Study Overview
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Brief Summary
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This study is an open-label, multiple-dose pharmacokinetic study of imipenem-relebactam conducted in 12 non-infected, obese ICU patients.

Official Title
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Impact of Obesity on the Pharmacokinetics of Imipenem-Relebactam in ICU Patients

Conditions
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Obesity, Critical Illness

Intervention / Treatment
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* Drug: Imipenem/Cilastatin/Relebactam 1.25g


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years of age Admitted to the ICU BMI ≥40 kg/m2 and/or total body weight ≥120 kg Provide a signed and dated written informed consent prior to study participation Exclusion Criteria: History of significant hypersensitivity reaction or intolerance to imipenem/cilastatin or carbapenem-based agents (doripenem, ertapenem, or meropenem +/- vaborbactam) History of seizures and/or receiving 1 or more anti-epileptic agent Serum creatinine ≥1.5 mg/dL Estimated creatinine clearance (CLCR) <60 mL/minute as determined by Cockcroft-Gault equation: Actively receiving antimicrobial therapy for treatment of a confirmed or suspected infection The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days prior to the first dose of study medication Positive serum pregnancy test (for women of childbearing potential) Currently breast feeding Has previously participated in this study Concomitant use of valproic acid or divalproex sodium Any other condition that may make the patient unsuitable for the study in the judgement of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacokinetic cohort<br>After at least 2 doses of study drug, serial blood samples will be collected from 12 non-infected, obese ICU patients to evaluate the pharmacokinetics of imipenem and relebactam in this population. | Drug: Imipenem/Cilastatin/Relebactam 1.25g<br>* Imipenem/cilastatin/relebactam is a combination beta-lactam/beta-lactamase inhibitor antimicrobial marketed under the brand name Recarbrio and the approved dose is 1.25g Q6h in patients with normal renal function. The individual components of this agent must be administered together and cannot be separated. Therefore, this constitutes only one intervention. Each subject will receive at least 2 doses of study drug.<br>* Other names: Recarbrio;|
| Experimental: Safety cohort<br>After at least 2 doses of study drug, safety will be monitored closely during study drug dosing and through 72 hours after the last dose is administered in the same 12 non-infected, obese ICU patients from the PK arm | Drug: Imipenem/Cilastatin/Relebactam 1.25g<br>* Imipenem/cilastatin/relebactam is a combination beta-lactam/beta-lactamase inhibitor antimicrobial marketed under the brand name Recarbrio and the approved dose is 1.25g Q6h in patients with normal renal function. The individual components of this agent must be administered together and cannot be separated. Therefore, this constitutes only one intervention. Each subject will receive at least 2 doses of study drug.<br>* Other names: Recarbrio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of imipenem and relebactam | Peak Plasma Concentration (Cmax) | 6 months | 
| Pharmacokinetic parameters of imipenem and relebactam | Area under the plasma concentration versus time curve (AUC) | 6 months | 
| Pharmacokinetic parameters of imipenem and relebactam | Total body clearance (CLt) | 6 months | 
| Pharmacokinetic parameters of imipenem and relebactam | Apparent volume of distribution (Vd) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of imipenem and relebactam | Monitoring for adverse drug events | 6 months |