A Safety and Tolerability Study of Doripenem in Patients With Abdominal Infections or Pneumonia
A Safety and Tolerability Study of Doripenem in Patients With Abdominal Infections or Pneumonia
The purpose of this study is to assess the safety and tolerability of doripenem compared to
 imipenem in Ventilator-assisted pneumonia and complicated Intra-abdominal Infection. The
 study population will include hospitalized patients (or patients resident in a chronic health
 care facility) who have a diagnosis of either Ventilator associated pneumonia or complicated
 Intra-abdominal Infection.
This is a randomized (study drug assigned by chance), open-label (all people involved know
 the identity of the intervention), multicenter study that will evaluate the safety and
 tolerability of doripenem (an antibiotic used to treat infections) in patients with
 ventilator-associated pneumonia (VAP) or complicated intra-abdominal infection (cIAI).
 Approximately 250 patients will be assigned in a 3:1 ratio to receive doripenem or
 imipenem/cilastatin (188 patients randomized to receive doripenem and 62 patients randomized
 to receive imipenem/cilastatin). Furthermore, patients who receive doripenem or
 imipenem/cilastatin will be stratified by disease (VAP or cIAI). Therefore, for reporting
 purposes, there will be 4 groups: Patients with VAP treated with doripenem, patients with VAP
 treated with imipenem/cilastatin, patients with cIAI treated with doripenem, and patients
 with cIAI treated with imipenem/cilastatin. Study drug will be administered intravenously
 (iv) (through a vein) for 7 to 14 days for patients with VAP and for 5 to 14 days for
 patients with cIAI. The maximum duration of study drug is 14 days. Vancomycin and/or amikacin
 may be added to the study drug regimen as adjunctive therapy for those patients who meet
 study specified criteria. The recommended dosage of vancomycin is 1 g every 12 hours
 administered by iv infusion. The addition of amikacin is at the discretion of the
 investigator for patients with VAP (not cIAI) and the recommended dosing regimen for amikacin
 is 15 mg/kg given iv once a day. Alternative amikacin regimens or other aminoglycoside
 regimens may be permitted. Safety will be assessed during the study by the monitoring of
 adverse events, evaluation of laboratory test results, and changes in vital signs. The
 primary endpoint of this study is to assess the overall incidence of treatment-emergent
 adverse events (TEAEs) from the initiation of the first infusion of study drug and up to 30
 days after the completion of study drug therapy. Treatment-emergent adverse events are
 defined as adverse events that occur or worsen between the initial infusion of study drug up
 to 30 days after the last dose of study drug. The hypothesis for this study is that doripenem
 has a similar safety profile to imipenem. Doripenem (1g at 8-hour intervals over a period of
 4 hours) or imipenem/cilastatin (1g at 8-hours over a period of 1 hour) will be administered
 by intravenous (iv) infusion (delivery of drug slowly into the vein over a period of time).
 Patients diagnosed with ventilator associated pneumonia (VAP) will be treated for 7 to 14
 days and patients with complicated intra-abdominal infections (cIAI) will be treated for 5 to
 14 days.
Inclusion Criteria:

 -  Patients must be hospitalized with a diagnosis of Ventilator-Assisted Pneumonia (VAP)
 or complicated Intra-Abdominal Infection (cIAI)

 -  Patients with VAP must have been hospitalized (or been in a chronic care facility) for
 >= 5 days, have received mechanical ventilation for >= 48 hours, have a Clinical
 Pulmonary Infection Score (CPIS) of >= 5, have new or progressive radiographic
 infiltrates (not related to another disease process)

 -  Patients with cIAI must have clinical evidence of intra-abdominal infection, abdominal
 pain or tenderness, localized or diffuse abdominal wall rigidity, mass, ileus or have
 a requirement for surgical intervention (e.g., laparotomy, laparoscopic surgery, or
 percutaneous draining of an abscess) within 24 hours of study entry

 Exclusion Criteria:

 -  Patients with a history of acute hepatic failure or acute decompensation of chronic
 hepatic failure, history of severe impairment of renal function, history of
 immunocompromising illness, acquired immunodeficiency syndrome (AIDS), or human
 immunodeficiency virus (HIV) with a CD4 count less than 200 cells/mL within the past 6
 months

 -  organ (including bone marrow) transplant recipients

 -  hematologic malignancy

 -  use of immunosuppressive therapy at screening, including use of high dose
 corticosteroids (e.g., > 40 mg prednisone or equivalent per day for > 2 weeks)

 -  history of any rapidly progressing disease or immediately life-threatening illness
 (including acute hepatic failure and septic shock)