Doripenem Intrapulmonary Pharmacokinetics in Healthy Adult Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Doripenem; Drug: Doripenem

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates, PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doripenem 500 mg	Drug: Doripenem; Intravenous 500 mg every (q) 8 hours for 3 doses; Other Names: Doribax; Drug: Doripenem; Intravenous 1000 mg q 8 hours for 3 doses; Other Names: Doribax
Experimental: Doripenem 1000 mg	Drug: Doripenem; Intravenous 500 mg every (q) 8 hours for 3 doses; Other Names: Doribax; Drug: Doripenem; Intravenous 1000 mg q 8 hours for 3 doses; Other Names: Doribax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Keith A. Rodvold
• Collaborators: Pulmonary Associates, PA
• Investigators: Principal Investigator: Keith A. Rodvold, Pharm.D., University of Illinois at Chicago; Principal Investigator: Mark H. Gotfried, M.D., Pulmonary Associates, PA; Principal Investigator: Larry H. Danziger, Pharm.D., University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: June 17, 2009
• First Submitted That Met QC Criteria: June 19, 2009
• First Posted (Estimate): June 22, 2009

Study Record Updates

• Last Update Posted (Estimate): March 14, 2013
• Last Update Submitted That Met QC Criteria: March 12, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: pharmacokinetics; Healthy adult subjects; epithelial lining fluid; doripenem; alveolar macrophages
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Doripenem
• Other Study ID Numbers: DORICPK4002