Clinical trial NCT00925392: Doripenem Intrapulmonary Pharmacokinetics in Healthy Adult Subjects
Official title: Doripenem Intrapulmonary Pharmacokinetics in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: doripenem
epithelial lining fluid
alveolar macrophages
pharmacokinetics
Healthy adult subjects
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: Pulmonary Associates, PA
First posted: 2009-06-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 32 hours
Secondary outcomes:
measure: 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.
timeFrame: 24 hours post end of doripenem administration
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
Study officials:
affiliation: University of Illinois at Chicago
name: Keith A. Rodvold, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Illinois at Chicago
name: Larry H. Danziger, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pulmonary Associates, PA
name: Mark H. Gotfried, M.D.
role: PRINCIPAL_INVESTIGATOR
References: