Doripenem Intrapulmonary Pharmacokinetics in Healthy Adult Subjects

Study Overview
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Brief Summary
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This study is being performed to measure the amount of the antibiotic doripenem (study drug) found in the fluid and cells of the lung and blood after receiving three doses of doripenem. The major objectives of this research are to see how much and for how long doripenem gets into the fluids and cells of the lungs of healthy adult subjects.

Detailed Description
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The primary objective of this descriptive study is to determine and compare the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AM) concentrations following multiple intravenous doses of doripenem in healthy, non-smoking adult subjects. In brief, each subject who qualifies for the study will be randomized to one of two dosing regimens: doripenem 500 mg or doripenem 1000 mg every 8 hours for a total of three intravenous doses. Each dose of doripenem will be administered as an intravenous infusion over 4 hours. Serial blood samples for determining plasma doripenem concentrations will be collected prior to and after the start of the intravenous infusion of the third doripenem dose. Each subject will undergo one standardized bronchoscopy with BAL in the outpatient bronchoscopy suite at one of four sampling times after the start of the intravenous infusion of the third doripenem dose. BAL collection will provide samples to determine drug concentration in ELF and AM. Safety will be assessed throughout the study by adverse event monitoring, clinical laboratory tests, and vital sign monitoring.

Official Title
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Doripenem Intrapulmonary Pharmacokinetics in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Doripenem
* Drug: Doripenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women at least 18 years of age who have no history of smoking within the last 1 year. Subjects must be healthy with no clinically important abnormalities in the medical history, physical examination, or laboratory values. Exclusion Criteria: Subjects must not have a history of allergic or other serious reactions to doripenem or any beta-lactam antibiotic, benzodiazepines or lidocaine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Health Services Research
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doripenem 500 mg<br> | Drug: Doripenem<br>* Intravenous 500 mg every (q) 8 hours for 3 doses<br>* Other names: Doribax;|
| Experimental: Doripenem 1000 mg<br> | Drug: Doripenem<br>* Intravenous 1000 mg q 8 hours for 3 doses<br>* Other names: Doribax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective is to determine and compare the plasma, epithelial lining fluid, and alveolar macrophages concentrations following multiple intravenous doses of doripenem in healthy, non-smoking adult subjects. |  | 32 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objective of this study is the assessment of safety and tolerability of doripenem as measured by the overall incidence of treatment-emergent adverse events. |  | 24 hours post end of doripenem administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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doripenem, epithelial lining fluid, alveolar macrophages, pharmacokinetics, Healthy adult subjects