Clinical trial NCT01265784: Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Complicated Intra-abdominal Infection
Lead sponsor: La Jolla Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2010-12-23
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit
timeFrame: TOC Visit (10-14 days after last dose of study drug)
Secondary outcomes:
measure: Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit
timeFrame: EOT Visit (4-14 days after first dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at TOC Visit
timeFrame: TOC Visit (10-14 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the Follow-up Visit
timeFrame: Follow-up Visit (28-42 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the EOT Visit
timeFrame: EOT Visit (4-14 days after first dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit
timeFrame: TOC Visit (10-14 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the Follow-up Visit
timeFrame: Follow-up Visit (28-42 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the EOT Visit
timeFrame: EOT Visit (4-14 days after first dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the TOC Visit
timeFrame: TOC Visit (10-14 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the Follow-up Visit
timeFrame: Follow-Up Visit (28-42 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the EOT Visit
timeFrame: EOT Visit (4-14 days after first dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the TOC Visit
timeFrame: TOC Visit (10-14 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the Follow-up Visit
timeFrame: Follow-up Visit (28-42 days after last dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the EOT Visit
timeFrame: EOT Visit (4-14 days after first dose of study drug)
measure: Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Follow-up Visit
timeFrame: Follow-up Visit (28-42 days after last dose of study drug)
measure: Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the EOT Visit
timeFrame: EOT Visit (4-14 days after first dose of study drug)
measure: Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit
timeFrame: TOC Visit (10-14 days after last dose of study drug)
measure: Microbiologic Response to TP-434 and Ertapenem in the ME Population at the EOT Visit
timeFrame: EOT Visit (4-14 days after first dose of study drug)
measure: Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit
timeFrame: TOC Visit (10-14 days after last dose of study drug)
measure: Pharmacokinetics: Maximum Concentration (Cmax) of TP-434
timeFrame: Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion
measure: Pharmacokinetics: Area Under the Concentration Time Curve From Time 0 to 12 Hours (AUC[0-12]) of TP-434
timeFrame: Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach VA Medical Center
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Byala
country: Bulgaria
facility: MHAT "Yulia Vrevska - Byala" EOOD, Byala
city: Pleven
country: Bulgaria
facility: UMHAT "Dr. Georgi Stranski" EAD, Pleven
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi" EAD, Plovdiv
city: Russe
country: Bulgaria
facility: MHAT "Russe" AD, Russe
city: Sofia
country: Bulgaria
facility: MHAT "Tokuda Hospital Sofia" AD, Sofia
city: Sofia
country: Bulgaria
facility: UMHAT "Tzaritza Yoanna" EAD, Sofia
city: Sofia
country: Bulgaria
facility: UMHATEM "N.I. Pirogov" EAD, Sofia
city: Sofia
country: Bulgaria
facility: UMHATEM "N.I.Pirogov" EAD, Sofia
city: Fort
country: India
facility: Bangalore Medical College and Research Institute, Victoria Hospital
state: Bangalore
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences and Research Centre
state: Kerala
city: Pune
country: India
facility: Sahyadri Munot Hospital
state: Maharashtra
city: Jaipur
country: India
facility: S.R. Kalla Memorial Gastro & General Hospital
state: Rajasthan
city: Ahmedabad
country: India
facility: HCG-Medisurge Hospitals Pvt. Ltd.
city: Bangalore
country: India
facility: Santosh Hospital
city: Bangalore
country: India
facility: K.R. Hospital
city: Bangalore
country: India
facility: M.S. Ramalah Medical College and Hospitals
city: Hyderabad
country: India
facility: Sai Vani Hospitals, Ltd.
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Jekabpils
country: Latvia
facility: Jekabpils Regional Hospital
city: Rezekne
country: Latvia
facility: Rezeknes Hospital
city: Valmiera
country: Latvia
facility: Vidzeme Hospital
city: Kaunas
country: Lithuania
facility: Kaunas Hospital
city: Kaunas
country: Lithuania
facility: Kaunas Clinical Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinics
city: Vilnius
country: Lithuania
facility: Vilnius City Clinical Hospital
city: Timisoara
country: Romania
facility: Emergency Clinical City Hospital
state: Timis
city: Bucharest
country: Romania
facility: "Dr. Carol Davila" Clinical Nephrology Hospital General Surgery Clinic
city: Bucharest
country: Romania
facility: Emergency Clinical Hospital Bucharest
city: Bucharest
country: Romania
facility: Coltea Clinical Hospital
city: Bucharest
country: Romania
facility: :Sfantul loan" Clinical Emergency Hospital
city: Bucharest
country: Romania
facility: University Emergency Hospital Bucharest
Study officials:
affiliation: Tetraphase Pharmaceuticals, Inc.
name: Patrick T Horn, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.