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

NCT ID: NCT01265784

Last Updated: 2022-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2012-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

TP-434

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Administered IV to maintain the blind.

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.

Group Type: EXPERIMENTAL

TP-434

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Administered IV to maintain the blind.

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.

Group Type: ACTIVE_COMPARATOR

Ertapenem

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Administered IV to maintain the blind.

Interventions

TP-434

Intervention Type: DRUG

Ertapenem

Intervention Type: DRUG

Placebo

Administered IV to maintain the blind.

Intervention Type: DRUG

Other Intervention Names

Eravacycline; Invanz

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tetraphase Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick T Horn, MD, PhD

Role: STUDY_DIRECTOR

Tetraphase Pharmaceuticals, Inc

Locations

Long Beach VA Medical Center

Long Beach, California, United States

Denver Health Medical Center

Denver, Colorado, United States

Henry Ford Hospital

Detroit, Michigan, United States

Barnes Jewish Hospital

St Louis, Missouri, United States

Mercury Street Medical Group

Butte, Montana, United States

MHAT "Yulia Vrevska - Byala" EOOD, Byala

Byala, , Bulgaria

UMHAT "Dr. Georgi Stranski" EAD, Pleven

Pleven, , Bulgaria

UMHAT "Sveti Georgi" EAD, Plovdiv

Plovdiv, , Bulgaria

MHAT "Russe" AD, Russe

Rousse, , Bulgaria

MHAT "Tokuda Hospital Sofia" AD, Sofia

Sofia, , Bulgaria

UMHAT "Tzaritza Yoanna" EAD, Sofia

Sofia, , Bulgaria

UMHATEM "N.I. Pirogov" EAD, Sofia

Sofia, , Bulgaria

UMHATEM "N.I.Pirogov" EAD, Sofia

Sofia, , Bulgaria

Bangalore Medical College and Research Institute, Victoria Hospital

Fort Mumbai, Bangalore, India

Amrita Institute of Medical Sciences and Research Centre

Kochi, Kerala, India

Sahyadri Munot Hospital

Pune, Maharashtra, India

S.R. Kalla Memorial Gastro & General Hospital

Jaipur, Rajasthan, India

HCG-Medisurge Hospitals Pvt. Ltd.

Ahmedabad, , India

Santosh Hospital

Bangalore, , India

K.R. Hospital

Bangalore, , India

M.S. Ramalah Medical College and Hospitals

Bangalore, , India

Sai Vani Hospitals, Ltd.

Hyderabad, , India

Daugavpils Regional Hospital

Daugavpils, , Latvia

Jekabpils Regional Hospital

Jēkabpils, , Latvia

Rezeknes Hospital

Rēzekne, , Latvia

Vidzeme Hospital

Valmiera, , Latvia

Kaunas Hospital

Kaunas, , Lithuania

Kaunas Clinical Hospital

Kaunas, , Lithuania

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

Klaipeda University Hospital

Klaipėda, , Lithuania

Vilnius University Hospital Santariskiu Clinics

Vilnius, , Lithuania

Vilnius City Clinical Hospital

Vilnius, , Lithuania

Emergency Clinical City Hospital

Timișoara, Timiș County, Romania

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

Bucharest, , Romania

Emergency Clinical Hospital Bucharest

Bucharest, , Romania

Coltea Clinical Hospital

Bucharest, , Romania

:Sfantul loan" Clinical Emergency Hospital

Bucharest, , Romania

University Emergency Hospital Bucharest

Bucharest, , Romania

Countries

United States; Bulgaria; India; Latvia; Lithuania; Romania

References

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.

Reference Type: DERIVED

PMID: 24342651 (View on PubMed)

Other Identifiers

TP-434-P2-cIAI-1

Identifier Type: -

Identifier Source: org_study_id