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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01265784
First received: December 21, 2010
Last updated: August 4, 2015
Last verified: August 2015
  Purpose
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).

Condition Intervention Phase
Complicated Intra-abdominal Infection
Drug: TP-434
Drug: Ertapenem
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Tetraphase Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: TOC Visit (10-14 days after last dose of study drug) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 143
Study Start Date: January 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: TP-434
Other Name: Eravacycline
Drug: Placebo
Administered IV to maintain the blind.
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.
Drug: TP-434
Other Name: Eravacycline
Drug: Placebo
Administered IV to maintain the blind.
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.
Drug: Ertapenem
Other Name: Invanz
Drug: Placebo
Administered IV to maintain the blind.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01265784

  Show 38 Study Locations
Sponsors and Collaborators
Tetraphase Pharmaceuticals, Inc.
Investigators
Study Director: Patrick T Horn, MD, PhD Tetraphase Pharmaceuticals, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01265784     History of Changes
Other Study ID Numbers: TP-434-P2-cIAI-1 
Study First Received: December 21, 2010
Results First Received: August 4, 2015
Last Updated: August 4, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Infection
Communicable Diseases
Intraabdominal Infections
Ertapenem
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on December 02, 2016