Sulopenem Versus Ertapenem for Complicated Intra-abdominal Infection (cIAI)

NCT03358576 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: IT001-303
• Study Type: interventional
• Target: 674
• Locations: 7 countries
• Sites: 42

Brief Summary

This is a prospective, Phase 3, randomized, multi-center, double-blind study of the efficacy, tolerability and safety of sulopenem followed by sulopenem-etzadroxil/probenecid versus ertapenem followed by ciprofloxacin-metronidazole for treatment of complicated intra-abdominal infections in adults.

Conditions

Intra Abdominal Infections

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Clinical Success

  Clinical response is defined as resolution in signs and symptoms of the index infection and no new symptoms, without the need for additional antibiotics or interventions

  Day 28 +/- 1 day

Secondary Outcomes (1)

• Percentage of Participants With Clinical Success

  Day 11-14 +/- 1 day

Study Arms (2)

Sulopenem

EXPERIMENTAL

Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment

Drug: Sulopenem-Etzadroxil/Probenecid; Drug: Sulopenem

Ertapenem

ACTIVE COMPARATOR

Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead

Drug: Ertapenem; Drug: Ciprofloxacin; Drug: Metronidazole; Drug: Amoxicillin-Clavulanate

Interventions

Ertapenem DRUG

Antibiotic for complicated intra-abdominal infection

Also known as: Invanz

Ertapenem

Sulopenem-Etzadroxil/Probenecid DRUG

Antibiotic for complicated intra-abdominal infection

Sulopenem

Ciprofloxacin DRUG

Antibiotic for complicated intra-abdominal infection

Also known as: Cipro

Ertapenem

Metronidazole DRUG

Antibiotic for complicated intra-abdominal infection

Also known as: Flagyl

Ertapenem

Amoxicillin-Clavulanate DRUG

Antibiotic for complicated intra-abdominal infection

Also known as: Augmentin

Ertapenem

Sulopenem DRUG

Antibiotic for complicated intra-abdominal infection

Sulopenem

Eligibility Criteria

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

You may qualify if:

• Patient or the patient's legally acceptable representative able to provide a signed written informed consent prior to any study-specific procedures.
• Adult patients ≥18 years of age
• EITHER:
• a. Intra-operative/post-operative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least 1 of the following diagnosed during the surgical intervention: i. Cholecystitis with gangrenous rupture or perforation or progression of the infection beyond the gallbladder wall ii. Diverticular disease with perforation or abscess iii. Appendiceal perforation or peri-appendiceal abscess iv. Traumatic perforation of the intestines, only if operated on \>12 hours after perforation occurs v. Secondary peritonitis (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites) vi. Intra-abdominal abscess (including of liver or spleen provided that there was extension beyond the organ with evidence of intraperitoneal involvement).
• OR:
• b. Pre-operative enrollment where one of the following surgical procedures are planned within 24 hours prior to the first dose of study drug: i. Open laparotomy, percutaneous drainage of an intra-abdominal abscess, or laparoscopic surgery.
• Evidence of systemic inflammatory indicators, with at least one of the following:
• i. Fever (defined as body temperature \>38°C) or hypothermia with a core body temperature \<35°C ii. Elevated white blood cell count (\>12,000 cells/mm3) iii. Drop in blood pressure (systolic BP must be \<90 mmHg without pressor support) iv. Increased heart rate (\>90 bpm) and respiratory rate (\>20 breaths/min) v. Hypoxia (oxygen saturation ≤90 percent on room air)
• Physical findings or symptoms consistent with intra-abdominal infection, with at least one of the following:
• i. Abdominal pain and/or tenderness, with or without rebound ii. Localized or diffuse abdominal wall rigidity iii. Abdominal mass iv. Nausea/vomiting v. Altered Mental Status
• Specimen/s from the surgical intervention were sent for culture.

You may not qualify if:

• Patient diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which the primary etiology was not likely to be infectious.
• Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation.
• Patient has simple cholecystitis or gangrenous cholecystitis without rupture, or simple appendicitis, or acute suppurative cholangitis; or infected necrotizing pancreatitis or pancreatic abscess.
• Patient whose surgery included staged abdominal repair, or "open abdomen" technique, or marsupialization.
• Patient known at study entry to have a complicated intra-abdominal infection caused by pathogens resistant to the study antimicrobial agents.
• Patient needed effective concomitant systemic antibacterials (oral, IV, or intramuscular) or antifungals in addition to those designated in the 2 study groups, except vancomycin, linezolid, or daptomycin if started for known or suspected methicillin-resistant Staphylococcus aureus (MRSA) or Enterococcus spp. as per clinical study protocol (CSP).
• Patient has perinephric infections or an indwelling peritoneal dialysis catheter.
• Patient has suspected intra-abdominal infections due to fungus, parasites (e.g., amoebic liver abscess), virus, or tuberculosis.
• Patient has a known history of serious allergy, hypersensitivity or any serious reaction to carbapenem antibiotics, or to other β-lactam antibiotics
• Patient known to have any of the following laboratory values as defined below:
• Hematocrit \<25% or hemoglobin \<8 g/dL
• Absolute neutrophil count \<1000/mm3
• Platelet count \<75,000/mm3
• Bilirubin \>3 x the upper limit of normal (ULN), unless isolated hyperbilirubinemia was directly related to the acute infection or known Gilbert's disease
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 x ULN values at Screening. Patients with elevations of AST and/or ALT up to 5 x ULN will be eligible if these elevations are acute and directly related to the infectious process being treated. This must be documented

Sponsors & Collaborators

• Iterum Therapeutics, International Limited: lead

Study Sites (42)

Medical Facility

Chula Vista, California, 91911, United States

Location

Medical Facility

Torrance, California, 90509, United States

Location

Medical Facility

Idaho Falls, Idaho, 83404, United States

Location

Medical Facility

Boston, Massachusetts, 02111, United States

Location

Medical Facility

Royal Oak, Michigan, 48073, United States

Location

Medical Facility

St Louis, Missouri, 63110, United States

Location

Medical Facility

Butte, Montana, 59701, United States

Location

Medical Facility

Lincoln, Nebraska, 68510, United States

Location

Medical Facility

Omaha, Nebraska, 68114, United States

Location

Medical Facility

Somers Point, New Jersey, 08244, United States

Location

Medical Facility

Columbus, Ohio, 43210, United States

Location

Medical Facility

Columbus, Ohio, 43215, United States

Location

Medical Facility

Blagoevgrad, 2700, Bulgaria

Location

Medical Facility

Lom, 3600, Bulgaria

Location

Medical Facility

Pleven, 5809, Bulgaria

Location

Medical Facility

Plovdiv, 4003, Bulgaria

Location

Medical Facility

Plovdiv, 4004, Bulgaria

Location

Medical Facility

Rousse, 7002, Bulgaria

Location

Medical Facility

Sofia, 1606, Bulgaria

Location

Medical Facility

Varna, 9000, Bulgaria

Location

Medical Facility

Varna, 9002, Bulgaria

Location

Medical Facility

Kohtla-Järve, 31025, Estonia

Location

Medical Facility

Tallinn, 10138, Estonia

Location

Medical Facility

Tallinn, 13419, Estonia

Location

Medical Facility

Tartu, 51014, Estonia

Location

Medical Facility

Viljandi, 71024, Estonia

Location

Medical Facility

Võru, 65526, Estonia

Location

Medical Facility

Gori, 1400, Georgia

Location

Medical Facility

Kutaisi, 4600, Georgia

Location

Medical Facility

Tbilisi, 0102, Georgia

Location

Medical Facility

Tbilisi, 0114, Georgia

Location

Medical Facility

Tbilisi, 0141, Georgia

Location

Medical Facility

Tbilisi, 0144, Georgia

Location

Medical Facility

Tbilisi, 0159, Georgia

Location

Medical Facility

Tbilisi, 0160, Georgia

Location

Medical Facility

Kaposvár, 7400, Hungary

Location

Medical Facility

Pécs, 7624, Hungary

Location

Medical Facility

Veszprém, 8200, Hungary

Location

Medical Facility

Daugavpils, 5417, Latvia

Location

Medical Facility

Rēzekne, 4600, Latvia

Location

Medical Facility

Riga, 1038, Latvia

Location

Medical Facility

Bielsk Podlaski, 17-100, Poland

Location

MeSH Terms

Conditions

Intraabdominal Infections

Interventions

Ertapenem; Probenecid; Ciprofloxacin; Metronidazole; Amoxicillin-Potassium Clavulanate Combination; sulopenem

Condition Hierarchy (Ancestors)

Infections

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfonamides; Sulfones; Sulfur Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Director, Clinical Development
• Organization: Iterum Therapeutics

saronin@iterumtx.com

18606614035

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: November 20, 2017
• First Posted: November 30, 2017
• Study Start: September 18, 2018
• Primary Completion: October 2, 2019
• Study Completion: October 2, 2019
• Last Updated: December 1, 2020
• Results First Posted: December 1, 2020

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); ES (6); GE (8); LA (3); PL (1); HU (3); BU (9)