Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections

Tetraphase Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Complicated Intra-abdominal Infection

Treatments: Drug: Placebo; Drug: Ertapenem; Drug: TP-434

Study type: Interventional

Funder types: Industry

Identifiers

NCT01265784

TP-434-P2-cIAI-1

Details and patient eligibility

About

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).

Enrollment: 143 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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143 participants in 3 patient groups

TP-434, 1.5 mg/kg q24h

Experimental group

Description:

TP-434 was administered intravenously (IV) at a dose of 1.5 milligrams per kilogram of body weight (mg/kg) every 24 hours (q24h) for a minimum of 4 days and a maximum of 14 days (7 days for participants in India). TP-434 treatment was to be stopped when symptoms of complicated intra-abdominal infection (cIAI) resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.

Treatment:

Drug: TP-434

Drug: Placebo

TP-434, 1.0 mg/kg q12h

Experimental group

Description:

TP-434 was administered IV at a dose of 1.0 mg/kg every 12 hours (q12h) for a minimum of 4 days and a maximum of 14 days (7 days for participants in India). TP-434 treatment was to be stopped when symptoms of cIAI resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.

Treatment:

Drug: TP-434

Drug: Placebo

Ertapenem, 1 g q24h

Active Comparator group

Description:

Ertapenem was administered IV at a dose of 1 gram (g) q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India). Ertapenem treatment was to be stopped when symptoms of cIAI resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.

Treatment:

Drug: Ertapenem

Drug: Placebo