Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections

A Multicenter, Double-Blind, Randomized, Phase 3 Study to Compare the Efficacy and Safety of Intravenous CXA-201 With That of Meropenem in Complicated Intraabdominal Infections

This is a Phase 3, multicenter, prospective, randomized, double-blind, double dummy study of CXA-201 Intravenous (IV) infusions (1500mg q8h) and metronidazole (500mg q8h) versus meropenem (1000mg q8h)for the treatment of adults with Complicated Intraabdominal Infections (cIAI).

Study Overview

• Status: Completed
• Conditions: Complicated Intra-abdominal Infection
• Intervention / Treatment: Drug: CXA-201 and metronidazole; Drug: Meropenem

Detailed Description

Approximately, 500 subjects will be enrolled into this study, randomized 1:1 to receive CXA-201 and metronidazole or comparator (meropenem). Subject participation will require a minimum commitment of 38 days and a maximum of 45 days. An End of Treatment (EOT) visit will occur within 24 hours following the last dose of study drug administration/drug discontinuation. A Test of Cure (TOC)/Safety visit will be conducted 26 to 30 days following the first dose of study drug administration. A Last Follow-up (LFU) visit will be conducted 38 to 45 days after the first dose of study drug.

• Study Type: Interventional
• Enrollment (Actual): 494
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina
  • Corrientes, Argentina
  • Santa Fe, Argentina
  • Buenos Aires
    • Ciudadelo-Buenos Aires, Buenos Aires, Argentina
    • General Rodriguez, Buenos Aires, Argentina
    • La Plata, Buenos Aires, Argentina
    • Loma Hermosa, Buenos Aires, Argentina
    • Lujan, Buenos Aires, Argentina
    • Merlo, Buenos Aires, Argentina
    • Tandil, Buenos Aires, Argentina
    • Vicente Lopez, Buenos Aires, Argentina
  • Entre Rios
    • Parana, Entre Rios, Argentina
• Bulgaria
  • Pleven, Bulgaria
  • Sofia, Bulgaria
  • Varna, Bulgaria
• Chile
  • Santiago, Chile
  • Cautin
    • Temuco, Cautin, Chile
• Croatia
  • Zagreb, Croatia
  • Dalmatia
    • Split, Dalmatia, Croatia
• Estonia
  • Kohtla-Jarve, Estonia
  • Tallinn, Estonia
  • Tartu, Estonia
• Germany
  • Baden-Weurttemberg
    • Freiburg, Baden-Weurttemberg, Germany
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany
• Hungary
  • Budapest, Hungary
  • Kaposvar, Hungary
  • Kecskemet, Hungary
  • Vac, Hungary
  • Bekes
    • Gyula, Bekes, Hungary
  • Csongrad
    • Szeged, Csongrad, Hungary
    • Szentes, Csongrad, Hungary
  • Gyor-Moson-Sopron
    • Gyor, Gyor-Moson-Sopron, Hungary
  • Zala
    • Zalaegerszerg, Zala, Hungary
• Israel
  • Beer Yahkov, Israel
  • Haifa, Israel
  • Sharon
    • Kfar Saba, Sharon, Israel
  • Tel Aviv
    • Tel Hashomer, Tel Aviv, Israel
• Korea, Republic of
  • Seoul, Korea, Republic of
  • Gangwon-Do
    • Wonju, Gangwon-Do, Korea, Republic of
  • Gyeonggi-Do
    • Incheon, Gyeonggi-Do, Korea, Republic of
    • Suwon-si, Gyeonggi-Do, Korea, Republic of
• Latvia
  • Liepaja, Latvia
  • Riga, Latvia
• Lithuania
  • Kaunas, Lithuania
  • Klaipeda, Lithuania
  • Siauliai, Lithuania
  • Vilnius, Lithuania
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
• Poland
  • Lodzkie
    • Lodz, Lodzkie, Poland
  • Lubelskie
    • Lubin, Lubelskie, Poland
  • Malopolskie
    • Krakow, Malopolskie, Poland
  • Mazowieckie
    • Wolomin, Mazowieckie, Poland
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland
• Serbia
  • Belgrade, Serbia
  • Krafujevac, Serbia
  • Nis, Serbia
  • Novi Sad, Serbia
• United States
  • Illinois
    • Springfield, Illinois, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Minnesota
    • Robbinsdale, Minnesota, United States
  • Ohio
    • Columbus, Ohio, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnoses of cIAI.
• Subject requires surgical intervention (e.g., laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of (before or after) the first dose of study drug.

Exclusion Criteria:

• Simple appendicitis; acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess; or pelvic infections.
• Complicated intraabdominal infection managed by staged abdominal repair (STAR), open abdomen technique including temporary closure of the abdomen, or any situation where infection source control is not likely to be achieved.
• Use of systemic antibiotic therapy for IAI for more than 24 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy.
• Have a concomitant infection at the time of randomization, which requires non-study systemic antibacterial therapy in addition to IV study drug therapy. (Drugs with only gram-positive activity [e.g., daptomycin, vancomycin, linezolid] are allowed).
• Severe impairment of renal function (estimated CrCl < 30 mL/min), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours).
• The presence of hepatic disease at baseline.
• Considered unlikely to survive the 4 to 5 week study period.
• Any rapidly-progressing disease or immediately life-threatening illness (including respiratory failure and septic shock).
• Have a documented history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibacterial (a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment), including cephalosporins, carbapenems, penicillins, or ß-lactamase inhibitors, or metronidazole, or nitroimidazole derivatives.
• Women who are pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CXA-201 and Metronidazole as treatment for cIAI	Drug: CXA-201 and metronidazole; CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
ACTIVE_COMPARATOR: Meropenem as treatment for cIAI	Drug: Meropenem; Meropenem IV infusion (1000mg q8h) for 4-14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects With Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population	Clinical cure is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.	TOC; 26-30 days after start of study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects With Microbiological Outcome of Success at the TOC Visit in the Microbiologically Evaluable (ME) Population	Success is eradication (absence of the baseline pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a subject who was assessed as a clinical cure) for each baseline pathogen	TOC; 26-30 days after start of study drug administration
The Percentage of Subjects With Clinical Response at End of Therapy (EOT) Visit in the MITT Population	Clinical response is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.	EOT; Within 24 hours of last study drug administration
The Percentage of Subjects With Clinical Response at End of Therapy in the ME Population	Clinical response is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.	EOT; Within 24 hours of last study drug administration
The Percentage of Subjects With Clinical Response at Long Term Follow-Up (LFU) in the MITT Population	Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit.	LFU; 38 to 45 days after first study drug administration
The Percentage of Subjects With Clinical Response at LFU Visit in the ME Population	Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit	LFU; 38 to 45 days after first study drug administration

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC
• Investigators: Study Director: Ellie Hershberger, Pharm.D, Cubist Pharmaceuticals LLC

Publications and helpful links

General Publications

• Popejoy MW, Long J, Huntington JA. Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam. BMC Infect Dis. 2017 May 2;17(1):316. doi: 10.1186/s12879-017-2414-9.
• Xiao Y, Tong ML, Liu LL, Lin LR, Chen MJ, Zhang HL, Zheng WH, Li SL, Lin HL, Lin ZF, Xing HQ, Niu JJ, Yang TC. Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study. BMC Infect Dis. 2017 Apr 26;17(1):310. doi: 10.1186/s12879-017-2339-3. Erratum In: BMC Infect Dis. 2017 May 22;17 (1):357.
• Kullar R, Wagenlehner FM, Popejoy MW, Long J, Yu B, Goldstein EJ. Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. J Antimicrob Chemother. 2017 Mar 1;72(3):900-905. doi: 10.1093/jac/dkw486.
• Miller B, Popejoy MW, Hershberger E, Steenbergen JN, Alverdy J. Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study. Antimicrob Agents Chemother. 2016 Jun 20;60(7):4387-90. doi: 10.1128/AAC.03074-15. Print 2016 Jul.
• Solomkin J, Hershberger E, Miller B, Popejoy M, Friedland I, Steenbergen J, Yoon M, Collins S, Yuan G, Barie PS, Eckmann C. Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI). Clin Infect Dis. 2015 May 15;60(10):1462-71. doi: 10.1093/cid/civ097. Epub 2015 Feb 10.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 23, 2011
• Primary Completion (ACTUAL): October 3, 2013
• Study Completion (ACTUAL): October 15, 2013

Study Registration Dates

• First Submitted: September 26, 2011
• First Submitted That Met QC Criteria: October 3, 2011
• First Posted (ESTIMATE): October 4, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 18, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: cIAI
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Intraabdominal Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Meropenem
• Other Study ID Numbers: 7625A-004; CXA-cIAI-10-09 (OTHER: Cubist Study Number); CXA-cIAI-10-08 (OTHER: Cubist Study number for 7625A-003)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf