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

Complicated Intra-abdominal Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01265784
• Other study ID #: TP-434-P2-cIAI-1
• Status: Completed
• Phase: Phase 2
• Start date: January 2011
• Est. completion date: May 2012

Study information

• Verified date: December 2021
• Source: La Jolla Pharmaceutical Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Complicated Intra-abdominal Infection
• Infections
• Intraabdominal Infections

Intervention

Drug:
• TP-434

• Ertapenem

• Placebo
Administered IV to maintain the blind.

Locations

Country	Name	City	State
Bulgaria	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	Russe
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
India	HCG-Medisurge Hospitals Pvt. Ltd.	Ahmedabad
India	K.R. Hospital	Bangalore
India	M.S. Ramalah Medical College and Hospitals	Bangalore
India	Santosh Hospital	Bangalore
India	Bangalore Medical College and Research Institute, Victoria Hospital	Fort	Bangalore
India	Sai Vani Hospitals, Ltd.	Hyderabad
India	S.R. Kalla Memorial Gastro & General Hospital	Jaipur	Rajasthan
India	Amrita Institute of Medical Sciences and Research Centre	Kochi	Kerala
India	Sahyadri Munot Hospital	Pune	Maharashtra
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Jekabpils Regional Hospital	Jekabpils
Latvia	Rezeknes Hospital	Rezekne
Latvia	Vidzeme Hospital	Valmiera
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Kaunas Clinical Hospital	Kaunas
Lithuania	Kaunas Hospital	Kaunas
Lithuania	Klaipeda University Hospital	Klaipeda
Lithuania	Vilnius City Clinical Hospital	Vilnius
Lithuania	Vilnius University Hospital Santariskiu Clinics	Vilnius
Romania	"Dr. Carol Davila" Clinical Nephrology Hospital General Surgery Clinic	Bucharest
Romania	:Sfantul loan" Clinical Emergency Hospital	Bucharest
Romania	Coltea Clinical Hospital	Bucharest
Romania	Emergency Clinical Hospital Bucharest	Bucharest
Romania	University Emergency Hospital Bucharest	Bucharest
Romania	Emergency Clinical City Hospital	Timisoara	Timis
United States	Mercury Street Medical Group	Butte	Montana
United States	Denver Health Medical Center	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Long Beach VA Medical Center	Long Beach	California
United States	Barnes Jewish Hospital	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Tetraphase Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  India,  Latvia,  Lithuania,  Romania, 

Outcome

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