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

NCT ID: NCT01110382

Last Updated: 2014-07-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2013-09-30

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.

Detailed Description

This is a randomized (study drug assigned by chance), double-blind (neither physician nor patient knows the name of the assigned study drugs), double-dummy (all patients are given both a placebo [salt solution] and study drug in alternating periods of time during the study), active comparator-controlled (compare the "test" treatment to standard-of-care therapy), multinational, multicenter study to evaluate the safety of the study drugs (doripenem and meropenem) administered by intravenous (iv) infusion (slow injection of drug solution into the vein over a period of time) in children aged 3 months to less than 18 years who are hospitalized with complicated intra abdominal infections (cIAI). Complicated intra abdominal infections include but are not limited to appendicitis with rupture and/or abscess (local collection of pus), acute (severe or intense) gastric, duodenal (beginning section of the small intestine), or gall bladder perforation (a hole in the wall of the stomach, small intestine, or gallbladder), and secondary peritonitis. The study will include 3 periods: a pretreatment (screening) period that will occur within 2 days prior to randomization (assignment of study drug), a treatment period of 5 to 14 days where patients will receive iv study drug treatment only or IV study therapy and a switch to oral antibiotic therapy, and a posttreatment period consisting of 2 study visits. The max duration of study drug therapy is 14 days. The total duration of the study is approximately 7 to 8 weeks. Safety and tolerability will be evaluated by examining the incidence, severity, and type of adverse events, changes in clinical laboratory tests, vital signs measurements, and findings from physical examinations observed during treatment and at each posttreatment visit. An independent monitoring committee (IDMC) will be established for this study to ensure that the safety of patients is not compromised. The IDMC will consist of individuals who are not associated with the conduct of the study, and will include but will not be limited to individuals with expertise relevant to the care of pediatric patients, and including at least one infectious disease physician and at least one statistician. Patients will receive IV Doripenem (20 mg/kg to 500 mg/dose) and meropenem placebo OR meropenem (20 mg/kg to 1 gram/dose) and doripenem placebo once every 8 hours for up to 14 days. If the patient's cIAI symptoms improve after 72 hours of treatment with iv study drug, the investigator may choose to stop iv study drug and switch the patient to an orally administered antibiotic (amoxicillin/clavulanate postassium) to complete the 5- to 14 day course of antibiotic therapy.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Doripenem

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.

Group Type: EXPERIMENTAL

Doripenem

Intervention Type: 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

Meropenem placebo

Intervention Type: 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.

Amoxicillin/clavulanate potassium

Intervention Type: 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.

Meropenem

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.

Group Type: EXPERIMENTAL

Meropenem

Intervention Type: 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

Doripenem placebo

Intervention Type: 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

Amoxicillin/clavulanate potassium

Intervention Type: 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.

Interventions

Doripenem

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

Intervention Type: DRUG

Meropenem placebo

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.

Intervention Type: DRUG

Meropenem

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

Intervention Type: DRUG

Doripenem placebo

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

Intervention Type: DRUG

Amoxicillin/clavulanate potassium

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC C. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

San Diego, California, United States

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

Cleveland, Ohio, United States

Toledo, Ohio, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Loma Hermosa, , Argentina

Paraná, Entre Ríos, , Argentina

Santa Fe, , Argentina

Passo Fundo, , Brazil

São Paulo, , Brazil

Santiago, , Chile

Valdivia X Región, , Chile

Bogotá, , Colombia

Floridablanca, , Colombia

Riga, , Latvia

Kaunas, , Lithuania

Vilnius, , Lithuania

Zona, , Panama

Countries

United States; Argentina; Brazil; Chile; Colombia; Latvia; Lithuania; Panama

Other Identifiers

DORIPED3001

Identifier Type: OTHER

Identifier Source: secondary_id

2009-015864-32

Identifier Type: OTHER

Identifier Source: secondary_id

CR016789

Identifier Type: -

Identifier Source: org_study_id