Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections
- Conditions
- Complicated Intra-abdominal Infection
- Interventions
- Registration Number
- NCT01265784
- Lead Sponsor
- Tetraphase Pharmaceuticals, Inc.
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TP-434, 1.5 mg/kg q24h TP-434 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. TP-434, 1.5 mg/kg q24h Placebo 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. TP-434, 1.0 mg/kg q12h Placebo 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. Ertapenem, 1 g q24h Placebo 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. TP-434, 1.0 mg/kg q12h TP-434 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. Ertapenem, 1 g q24h Ertapenem 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.
- Primary Outcome Measures
Name Time Method Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit TOC Visit (10-14 days after last dose of study drug) Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection \[cIAI\], persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (Test-of-Cure \[TOC\] assessment was not available, death unrelated to cIAI, or some other reason).
- Secondary Outcome Measures
Name Time Method Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the Follow-up Visit Follow-up Visit (28-42 days after last dose of study drug) Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the EOT Visit EOT Visit (4-14 days after first dose of study drug) Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the TOC Visit TOC Visit (10-14 days after last dose of study drug) Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit EOT Visit (4-14 days after first dose of study drug) Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at TOC Visit TOC Visit (10-14 days after last dose of study drug) Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the EOT Visit EOT Visit (4-14 days after first dose of study drug) Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the TOC Visit TOC Visit (10-14 days after last dose of study drug) Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the Follow-up Visit Follow-up Visit (28-42 days after last dose of study drug) Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the EOT Visit EOT Visit (4-14 days after first dose of study drug) Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Follow-up Visit Follow-up Visit (28-42 days after last dose of study drug) Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the EOT Visit EOT Visit (4-14 days after first dose of study drug) Microbiological response was classified as favorable (eradication or presumed eradication), unfavorable (persistence, presumed persistence, superinfection, or new infection), or indeterminate (assessment not possible).
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit TOC Visit (10-14 days after last dose of study drug) Microbiologic Response to TP-434 and Ertapenem in the ME Population at the EOT Visit EOT Visit (4-14 days after first dose of study drug) Pharmacokinetics: Area Under the Concentration Time Curve From Time 0 to 12 Hours (AUC[0-12]) of TP-434 Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit TOC Visit (10-14 days after last dose of study drug) Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the Follow-up Visit Follow-up Visit (28-42 days after last dose of study drug) Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the EOT Visit EOT Visit (4-14 days after first dose of study drug) Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the Follow-up Visit Follow-Up Visit (28-42 days after last dose of study drug) Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit TOC Visit (10-14 days after last dose of study drug) Pharmacokinetics: Maximum Concentration (Cmax) of TP-434 Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion
Trial Locations
- Locations (38)
MHAT "Russe" AD, Russe
🇧🇬Russe, Bulgaria
Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Long Beach VA Medical Center
🇺🇸Long Beach, California, United States
UMHAT "Sveti Georgi" EAD, Plovdiv
🇧🇬Plovdiv, Bulgaria
Amrita Institute of Medical Sciences and Research Centre
🇮🇳Kochi, Kerala, India
UMHATEM "N.I.Pirogov" EAD, Sofia
🇧🇬Sofia, Bulgaria
MHAT "Tokuda Hospital Sofia" AD, Sofia
🇧🇬Sofia, Bulgaria
Denver Health Medical Center
🇺🇸Denver, Colorado, United States
HCG-Medisurge Hospitals Pvt. Ltd.
🇮🇳Ahmedabad, India
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
UMHAT "Tzaritza Yoanna" EAD, Sofia
🇧🇬Sofia, Bulgaria
MHAT "Yulia Vrevska - Byala" EOOD, Byala
🇧🇬Byala, Bulgaria
M.S. Ramalah Medical College and Hospitals
🇮🇳Bangalore, India
Santosh Hospital
🇮🇳Bangalore, India
Daugavpils Regional Hospital
🇱🇻Daugavpils, Latvia
Kaunas Clinical Hospital
🇱🇹Kaunas, Lithuania
Sai Vani Hospitals, Ltd.
🇮🇳Hyderabad, India
Sahyadri Munot Hospital
🇮🇳Pune, Maharashtra, India
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
🇱🇹Kaunas, Lithuania
Mercury Street Medical Group
🇺🇸Butte, Montana, United States
Vidzeme Hospital
🇱🇻Valmiera, Latvia
Emergency Clinical Hospital Bucharest
🇷🇴Bucharest, Romania
Klaipeda University Hospital
🇱🇹Klaipeda, Lithuania
:Sfantul loan" Clinical Emergency Hospital
🇷🇴Bucharest, Romania
Vilnius City Clinical Hospital
🇱🇹Vilnius, Lithuania
"Dr. Carol Davila" Clinical Nephrology Hospital General Surgery Clinic
🇷🇴Bucharest, Romania
UMHAT "Dr. Georgi Stranski" EAD, Pleven
🇧🇬Pleven, Bulgaria
UMHATEM "N.I. Pirogov" EAD, Sofia
🇧🇬Sofia, Bulgaria
Bangalore Medical College and Research Institute, Victoria Hospital
🇮🇳Fort, Bangalore, India
S.R. Kalla Memorial Gastro & General Hospital
🇮🇳Jaipur, Rajasthan, India
K.R. Hospital
🇮🇳Bangalore, India
Jekabpils Regional Hospital
🇱🇻Jekabpils, Latvia
Kaunas Hospital
🇱🇹Kaunas, Lithuania
Rezeknes Hospital
🇱🇻Rezekne, Latvia
Vilnius University Hospital Santariskiu Clinics
🇱🇹Vilnius, Lithuania
Emergency Clinical City Hospital
🇷🇴Timisoara, Timis, Romania
Coltea Clinical Hospital
🇷🇴Bucharest, Romania
University Emergency Hospital Bucharest
🇷🇴Bucharest, Romania