Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections
Condition: Complicated Intra-abdominal Infection
MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections
Intervention: TP-434; Ertapenem; Placebo
Intervention description: Administered IV to maintain the blind.
Intervention MeSH terms: Ertapenem
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 143.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a Phase 2, randomized, double-blind, double-dummy, multicenter, prospective study to
      assess the efficacy, safety, and pharmacokinetics of two dose regimens of TP-434 compared
      with ertapenem in the treatment of adult community-acquired complicated intra-abdominal
      infections (cIAIs).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Abdominal pain/discomfort with onset prior to hospitalization

          -  Evidence of a systemic inflammatory response

          -  Physical findings consistent with intra-abdominal infection (IAI)

          -  Clinical diagnosis of community-acquired IAI requiring urgent surgical or percutaneous
             intervention and not expected to require antibacterial therapy for longer than 14 days

          -  Body mass index (BMI) of ≤ 30 kilograms per square meter (kg/m^2)

          -  Able to provide informed consent. If the participant is unable to provide informed
             consent, the participant's legally acceptable representative may provide written
             consent in accordance with institutional guidelines

          -  If female, not pregnant or nursing or, if of child-bearing potential either: will
             commit to use at least two medically accepted, effective methods of birth control (for
             example, condom, oral contraceptive, indwelling intrauterine device, hormonal
             implant/patch, injections, approved cervical ring) during study drug dosing and for 90
             days following last study drug dose or practicing sexual abstinence

        Exclusion Criteria:

          -  Symptoms related to diagnosis of complicated appendicitis (if current diagnosis) for <
             24 hours prior to current hospitalization

          -  Previously hospitalized or admitted to a healthcare facility within the last 6 months

          -  Managed by Staged Abdominal Repair or other open abdomen technique

          -  Known at study entry to have an IAI caused by a pathogen(s) resistant to both study
             drug antibiotics

          -  Acute Physiology and Chronic Health Evaluation (APACHE) II score > 25

          -  Unlikely to survive the 6-8 week study period

          -  Any rapidly-progressing disease or immediately life-threatening illness, including
             acute hepatic failure, respiratory failure and septic shock

          -  Requirement for vasopressors at therapeutic dosages

          -  Renal failure

          -  Presence or possible signs of hepatic disease

          -  Hematocrit < 25% or hemoglobin < 8 grams per deciliter (g/dL)

          -  Neutropenia with absolute neutrophil count < 1000 cells per cubic millimeter (mm^3)

          -  Platelet count < 50,000/mm3

          -  Abnormal coagulation tests or participant on anticoagulants

          -  Immunocompromised condition, including known human immunodeficiency virus (HIV)
             positivity or acquired immune deficiency syndrome (AIDS), organ (bone marrow)
             transplant recipients, and hematological malignancy. Immunosuppressive therapy,
             including use of high-dose corticosteroids (for example, > 40 milligrams [mg]
             prednisone or equivalent per day for greater than 2 weeks)

          -  History of hypersensitivity reactions to tetracyclines or carbapenems

          -  Participation in any investigational drug or device study within 30 days prior to
             study entry

          -  Known or suspected central nervous system (CNS) disorder that may predispose to
             seizures or lower seizure threshold

          -  Previously received TP-434 in a clinical trial

          -  More than 24 hours duration of systemic antibiotic coverage for current condition

          -  Received ertapenem or any other carbapenem, or tigecycline for the current infection

          -  Need for concomitant systemic antimicrobial agents other than study drug or received
             systemic (IV or oral) antibiotics in the last 3 months

          -  Refusal of mechanical ventilation, dialysis or hemofiltration, cardioversion or any
             other resuscitative measures and drug/fluid therapy at time of consent

          -  Known or suspected inflammatory bowel disease or associated visceral abscess