A Safety and Tolerability Study of Doripenem Compared With Meropenem in Children Hospitalized With Complicated Intra-abdominal Infections

NCT01110382 | Terminated Phase 3 Results DMC

• 3 other identifiers: CR016789DORIPED30012009-015864-32
• Study Type: interventional
• Target: 41
• Locations: 8 countries
• Sites: 19

Brief Summary

The purpose of the study is to evaluate the safety and tolerability of doripenem compared with meropenem in children hospitalized with complicated intra-abdominal infections.

Conditions

Abscess, Intra-Abdominal; Abdominal Abscess; Abdomen, Acute; Abdominal Pain; Appendicitis; Rupture; Infection; Intestinal Perforation; Peritonitis; Ileus

Keywords

Anti-Infective Agents; Doripenem; Meropenem; Child, Hospitalized; Complicated Intra-Abdominal Infections

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit

  The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.

  TOC (7 to 14 days after the last dose of study medication therapy)

Secondary Outcomes (6)

• The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit

  EIV (within 24 hours after completion of the last dose of IV study medication therapy)

• The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit

  LFU (28 to 42 days after the last dose of study medication therapy)

• The Number of Participants With Favorable Per-participant Microbiological Response

  EIV (within 24 hours after completion of the last dose of IV study medication therapy), TOC (7 to 14 days after the last dose of study medication therapy), and LFU (28 to 42 days after the last dose of study medication therapy)

• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit

  EIV (within 24 hours after completion of the last dose of IV study medication therapy)

• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit

  TOC (7 to 14 days after the last dose of study medication therapy)

Study Arms (2)

Doripenem

EXPERIMENTAL

Doripenem 20 mg/kg per dose (up to 500 mg/dose)will be administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.

Drug: Doripenem; Drug: Meropenem placebo; Drug: Amoxicillin/clavulanate potassium

Meropenem

EXPERIMENTAL

Meropenem 20 mg/kg per dose (up to 1 g/dose) will be administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.

Drug: Meropenem; Drug: Doripenem placebo; Drug: Amoxicillin/clavulanate potassium

Interventions

Doripenem DRUG

Type=once every 8 hours infused over 60 minutes, Unit=mg, Number=20mg/kg up to 500mg/dose, Form=solution for infusion, Route-intravenous use. At least 3 days of iv doripenem administered every 8 hours immediately after meropenem placebo for up to 14 days

Doripenem

Meropenem placebo DRUG

Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem for up to 14 days.

Doripenem

Meropenem DRUG

Type=once every 8 hours infused over 30 minutes, Unit=mg, Number=20 mg/kg to 1 gram per dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv meropenem administered every 8 hours immediately before doripenem placebo for up to 14 days

Meropenem

Doripenem placebo DRUG

Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately after each iv infusion of meropenem for up to 14 days

Meropenem

Amoxicillin/clavulanate potassium DRUG

Form=suspension or tablets, Route=oral (by mouth), may be administered at the discretion of the investigator once every 12 hours for up to 14 days following IV therapy with doripenem or meropenem.

Doripenem; Meropenem

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients who are eligible for the study must have clinical evidence of cIAI
• Require surgical intervention (eg, laparotomy, laparoscopic surgery, or percutaneous drainage) to manage the cIAI
• Require antibacterial therapy for 5 to 14 days in addition to the surgical intervention
• Must, based on the judgment of the investigator, require hospitalization initially and antibacterial therapy for 5 to 14 days in addition to surgical intervention for the treatment of the current cIAI. (Note that the patient must require at least 3 days of IV antibiotic therapy initially)
• Have a signed informed consent form completed by the patient's parent or legal representative (and a signed assent form obtained from patients who are capable of providing assent, typically, children 7 years of age and older)

You may not qualify if:

• Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other beta-lactam antibiotics
• concomitant infection including but not limited to suspected or confirmed meningitis or central nervous system infection requiring systemic antibiotic or antifungal therapy in addition to the iv study drug therapy at the time of randomization
• Receipt of nonstudy systemic antibiotic therapy for cIAI for more than 24 hours immediately preceding the start of the infusion of the first dose of iv study drug therapy
• Have a diagnosis of abdominal wall abscess confined to musculature of the abdominal wall, small bowel obstruction or ischemic bowel disease without perforation, traumatic bowel perforation requiring surgery within 12 hours of perforation, or perforation of gastroduodenal ulcers requiring surgery within 24 hours of perforation (these are considered situations of peritoneal soiling before the infection has become established)
• Have simple (noncomplicated), nonperforated appendicitis or gangrenous appendicitis without rupture into the peritoneal cavity identified during a surgical procedure OR presence of spontaneous bacterial peritonitis or peritonitis associated with cirrhosis or chronic ascites
• Known at the time of randomization to have a cIAI caused by at least one pathogen that is nonsusceptible to doripenem or meropenem
• Presence of any of the following clinically significant laboratory abnormalities: Hematocrit of less than 20%, absolute neutrophil count (ANC) \<500 cells/µL, platelet count \<40,000 cells/µL, serum alanine aminotransferase or aspartate aminotransferase (AST) or total bilirubin 5 times or greater the age-specific upper limit of normal (ULN) or acute/chronic renal insufficiency with a baseline creatinine clearance \<50 mL per minute or requires dialysis therapy for any reason
• Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6 months before randomization

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (19)

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Washington D.C., District of Columbia, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Toledo, Ohio, United States

Location

Unknown Facility

Buenos Aires, Argentina

Location

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Córdoba, Argentina

Location

Unknown Facility

Loma Hermosa, Argentina

Location

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Paraná, Entre Ríos, Argentina

Location

Unknown Facility

Santa Fe, Argentina

Location

Unknown Facility

Passo Fundo, Brazil

Location

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São Paulo, Brazil

Location

Unknown Facility

Santiago, Chile

Location

Unknown Facility

Valdivia X Región, Chile

Location

Unknown Facility

Bogotá, Colombia

Location

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Floridablanca, Colombia

Location

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Riga, Latvia

Location

Unknown Facility

Kaunas, Lithuania

Location

Unknown Facility

Vilnius, Lithuania

Location

Unknown Facility

Zona, Panama

Location

MeSH Terms

Conditions

Abdominal Abscess; Abdomen, Acute; Abdominal Pain; Appendicitis; Rupture; Infections; Intestinal Perforation; Peritonitis; Ileus

Interventions

Doripenem; Meropenem; Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Abscess; Suppuration; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Intraabdominal Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases; Wounds and Injuries; Peritoneal Diseases; Intestinal Obstruction

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thienamycins; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

This study was terminated early due to business reasons and not related to safety concerns or issues. As such, the limited enrollment precludes a meaningful conclusion about the efficacy and safety of doripenem compared with meropenem.

Results Point of Contact

• Title: Therapeutic Areas Director
• Organization: Janssen R&D US

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC C. Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• 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: April 15, 2010
• First Posted: April 26, 2010
• Study Start: December 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 15, 2014
• Results First Posted: July 2, 2014

Record last verified: 2014-07

Locations

BR (2); CL (2); LA (1); PA (1); CO (2); US (4); AR (5); LI (2)