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

December 16, 2021 updated by: Tetraphase Pharmaceuticals, Inc.

A Phase 2, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy, Safety, and PK of 2 Dose Regimens of TP-434 Compared With Ertapenem in Adult Community-Acquired Complicated Intra-abdominal Infections

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).

Study Overview

Study Type

Interventional

Enrollment (Actual)

143

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Byala, Bulgaria, 7100
        • MHAT "Yulia Vrevska - Byala" EOOD, Byala
      • Pleven, Bulgaria, 5800
        • UMHAT "Dr. Georgi Stranski" EAD, Pleven
      • Plovdiv, Bulgaria, 4000
        • UMHAT "Sveti Georgi" EAD, Plovdiv
      • Russe, Bulgaria, 7002
        • MHAT "Russe" AD, Russe
      • Sofia, Bulgaria, 1407
        • MHAT "Tokuda Hospital Sofia" AD, Sofia
      • Sofia, Bulgaria, 1527
        • UMHAT "Tzaritza Yoanna" EAD, Sofia
      • Sofia, Bulgaria, 1606
        • UMHATEM "N.I. Pirogov" EAD, Sofia
      • Sofia, Bulgaria, 1606
        • UMHATEM "N.I.Pirogov" EAD, Sofia
      • Ahmedabad, India, 380006
        • HCG-Medisurge Hospitals Pvt. Ltd.
      • Bangalore, India, 560005
        • Santosh Hospital
      • Bangalore, India, 560050
        • K.R. Hospital
      • Bangalore, India, 560054
        • M.S. Ramalah Medical College and Hospitals
      • Hyderabad, India, 500029
        • Sai Vani Hospitals, Ltd.
    • Bangalore
      • Fort, Bangalore, India, 560002
        • Bangalore Medical College and Research Institute, Victoria Hospital
    • Kerala
      • Kochi, Kerala, India, 682041
        • Amrita Institute of Medical Sciences and Research Centre
    • Maharashtra
      • Pune, Maharashtra, India, 411042
        • Sahyadri Munot Hospital
    • Rajasthan
      • Jaipur, Rajasthan, India
        • S.R. Kalla Memorial Gastro & General Hospital
      • Daugavpils, Latvia, LV-5417
        • Daugavpils Regional Hospital
      • Jekabpils, Latvia, LV 5201
        • Jekabpils Regional Hospital
      • Rezekne, Latvia, LV-4601
        • Rezeknes Hospital
      • Valmiera, Latvia, LV-4201
        • Vidzeme Hospital
      • Kaunas, Lithuania, LT-50009
        • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
      • Kaunas, Lithuania, LT-47144
        • Kaunas Clinical Hospital
      • Kaunas, Lithuania, LT-45130
        • Kaunas Hospital
      • Klaipeda, Lithuania, LT-92288
        • Klaipeda university hospital
      • Vilnius, Lithuania, LT-10207
        • Vilnius City Clinical Hospital
      • Vilnius, Lithuania, LT-08661
        • Vilnius University Hospital Santariskiu Clinics
      • Bucharest, Romania, 030171
        • Coltea Clinical Hospital
      • Bucharest, Romania, 010701
        • "Dr. Carol Davila" Clinical Nephrology Hospital General Surgery Clinic
      • Bucharest, Romania, 014461
        • Emergency Clinical Hospital Bucharest
      • Bucharest, Romania, 042122
        • :Sfantul loan" Clinical Emergency Hospital
      • Bucharest, Romania, 050098
        • University Emergency Hospital Bucharest
    • Timis
      • Timisoara, Timis, Romania, 300079
        • Emergency Clinical City Hospital
    • California
      • Long Beach, California, United States, 90822
        • Long Beach VA Medical Center
    • Colorado
      • Denver, Colorado, United States, 80204
        • Denver Health Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Barnes Jewish Hospital
    • Montana
      • Butte, Montana, United States, 59701
        • Mercury Street Medical Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TP-434, 1.5 mg/kg q24h
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.
Administered IV to maintain the blind.
Other Names:
  • Eravacycline
Experimental: TP-434, 1.0 mg/kg q12h
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.
Administered IV to maintain the blind.
Other Names:
  • Eravacycline
Active Comparator: Ertapenem, 1 g q24h
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.
Administered IV to maintain the blind.
Other Names:
  • Invanz

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit
Time Frame: 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).
TOC Visit (10-14 days after last dose of study drug)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit
Time Frame: EOT Visit (4-14 days after first dose of study drug)
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
Time Frame: TOC Visit (10-14 days after last dose of study drug)
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 Follow-up Visit
Time Frame: Follow-up Visit (28-42 days after last dose of study drug)
Follow-up Visit (28-42 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
Time Frame: EOT Visit (4-14 days after first dose of study drug)
EOT Visit (4-14 days after first dose of study drug)
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit
Time Frame: TOC Visit (10-14 days after last dose of study drug)
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
Time Frame: Follow-up Visit (28-42 days after last dose of study drug)
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
Time Frame: EOT Visit (4-14 days after first dose of study drug)
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
Time Frame: TOC Visit (10-14 days after last dose of study drug)
TOC Visit (10-14 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 Follow-up Visit
Time Frame: Follow-Up Visit (28-42 days after last dose of study drug)
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
Time Frame: EOT Visit (4-14 days after first dose of study drug)
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
Time Frame: TOC Visit (10-14 days after last dose of study drug)
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
Time Frame: Follow-up Visit (28-42 days after last dose of study drug)
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
Time Frame: EOT Visit (4-14 days after first dose of study drug)
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
Time Frame: Follow-up Visit (28-42 days after last dose of study drug)
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
Time Frame: 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).
EOT Visit (4-14 days after first dose of study drug)
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit
Time Frame: TOC Visit (10-14 days after last dose of study drug)
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
Time Frame: EOT Visit (4-14 days after first dose of study drug)
EOT Visit (4-14 days after first dose of study drug)
Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit
Time Frame: TOC Visit (10-14 days after last dose of study drug)
TOC Visit (10-14 days after last dose of study drug)
Pharmacokinetics: Maximum Concentration (Cmax) of TP-434
Time Frame: Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion
Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion
Pharmacokinetics: Area Under the Concentration Time Curve From Time 0 to 12 Hours (AUC[0-12]) of TP-434
Time Frame: Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion
Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

December 21, 2010

First Submitted That Met QC Criteria

December 22, 2010

First Posted (Estimate)

December 23, 2010

Study Record Updates

Last Update Posted (Actual)

January 6, 2022

Last Update Submitted That Met QC Criteria

December 16, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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