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

NCT01265784 | Completed Phase 2 Results DMC

• 1 other identifier: TP-434-P2-cIAI-1
• Study Type: interventional
• Target: 143
• Locations: 6 countries
• Sites: 38

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).

Conditions

Complicated Intra-abdominal Infection

Outcome Measures

Primary Outcomes (1)

• Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit

  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 Outcomes (20)

• 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 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 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 Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit

  TOC Visit (10-14 days after last dose of study drug)

Study Arms (3)

TP-434, 1.5 mg/kg q24h

EXPERIMENTAL

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; Drug: Placebo

TP-434, 1.0 mg/kg q12h

EXPERIMENTAL

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; Drug: Placebo

Ertapenem, 1 g q24h

ACTIVE COMPARATOR

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; Drug: Placebo

Interventions

TP-434 DRUG

Also known as: Eravacycline

TP-434, 1.0 mg/kg q12h; TP-434, 1.5 mg/kg q24h

Ertapenem DRUG

Also known as: Invanz

Ertapenem, 1 g q24h

Placebo DRUG

Administered IV to maintain the blind.

Ertapenem, 1 g q24h; TP-434, 1.0 mg/kg q12h; TP-434, 1.5 mg/kg q24h

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Tetraphase Pharmaceuticals, Inc: lead

Study Sites (38)

Long Beach VA Medical Center

Long Beach, California, 90822, United States

Location

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Mercury Street Medical Group

Butte, Montana, 59701, United States

Location

MHAT "Yulia Vrevska - Byala" EOOD, Byala

Byala, 7100, Bulgaria

Location

UMHAT "Dr. Georgi Stranski" EAD, Pleven

Pleven, 5800, Bulgaria

Location

UMHAT "Sveti Georgi" EAD, Plovdiv

Plovdiv, 4000, Bulgaria

Location

MHAT "Russe" AD, Russe

Rousse, 7002, Bulgaria

Location

MHAT "Tokuda Hospital Sofia" AD, Sofia

Sofia, 1407, Bulgaria

Location

UMHAT "Tzaritza Yoanna" EAD, Sofia

Sofia, 1527, Bulgaria

Location

UMHATEM "N.I. Pirogov" EAD, Sofia

Sofia, 1606, Bulgaria

Location

UMHATEM "N.I.Pirogov" EAD, Sofia

Sofia, 1606, Bulgaria

Location

Bangalore Medical College and Research Institute, Victoria Hospital

Fort Mumbai, Bangalore, 560002, India

Location

Amrita Institute of Medical Sciences and Research Centre

Kochi, Kerala, 682041, India

Location

Sahyadri Munot Hospital

Pune, Maharashtra, 411042, India

Location

S.R. Kalla Memorial Gastro & General Hospital

Jaipur, Rajasthan, India

Location

HCG-Medisurge Hospitals Pvt. Ltd.

Ahmedabad, 380006, India

Location

Santosh Hospital

Bangalore, 560005, India

Location

K.R. Hospital

Bangalore, 560050, India

Location

M.S. Ramalah Medical College and Hospitals

Bangalore, 560054, India

Location

Sai Vani Hospitals, Ltd.

Hyderabad, 500029, India

Location

Daugavpils Regional Hospital

Daugavpils, LV-5417, Latvia

Location

Jekabpils Regional Hospital

Jēkabpils, LV 5201, Latvia

Location

Rezeknes Hospital

Rēzekne, LV-4601, Latvia

Location

Vidzeme Hospital

Valmiera, LV-4201, Latvia

Location

Kaunas Hospital

Kaunas, LT-45130, Lithuania

Location

Kaunas Clinical Hospital

Kaunas, LT-47144, Lithuania

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, LT-50009, Lithuania

Location

Klaipeda University Hospital

Klaipėda, LT-92288, Lithuania

Location

Vilnius University Hospital Santariskiu Clinics

Vilnius, LT-08661, Lithuania

Location

Vilnius City Clinical Hospital

Vilnius, LT-10207, Lithuania

Location

Emergency Clinical City Hospital

Timișoara, Timiș County, 300079, Romania

Location

"Dr. Carol Davila" Clinical Nephrology Hospital General Surgery Clinic

Bucharest, 010701, Romania

Location

Emergency Clinical Hospital Bucharest

Bucharest, 014461, Romania

Location

Coltea Clinical Hospital

Bucharest, 030171, Romania

Location

:Sfantul loan" Clinical Emergency Hospital

Bucharest, 042122, Romania

Location

University Emergency Hospital Bucharest

Bucharest, 050098, Romania

Location

Related Publications (1)

• Solomkin JS, Ramesh MK, Cesnauskas G, Novikovs N, Stefanova P, Sutcliffe JA, Walpole SM, Horn PT. Phase 2, randomized, double-blind study of the efficacy and safety of two dose regimens of eravacycline versus ertapenem for adult community-acquired complicated intra-abdominal infections. Antimicrob Agents Chemother. 2014;58(4):1847-54. doi: 10.1128/AAC.01614-13. Epub 2013 Dec 16.

  PMID: 24342651 DERIVED

MeSH Terms

Interventions

eravacycline; Ertapenem

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Development Officer
• Organization: La Jolla Pharmaceutical Company

ljpcregulatory@ljpc.com

+1.617.715.3600

Study Officials

• Patrick T Horn, MD, PhD

  Tetraphase Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2010
• First Posted: December 23, 2010
• Study Start: January 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: January 6, 2022
• Results First Posted: September 4, 2015

Record last verified: 2021-12

Locations

LI (6); BU (8); RO (6); US (5); IN (9); LA (4)