E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complicated Intra-Abdominal Infections |
|
E.1.1.1 | Medical condition in easily understood language |
Abscess, Intra-Abdominal;
Abdominal Abscess;
Abdomen, Acute;
Abdominal Pain;
Appendicitis;
Rupture;
Infection;
Intestinal Perforation;
Peritonitis;
Ileus. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056570 |
E.1.2 | Term | Intra-abdominal infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to establish the safety and tolerability profile of doripenem compared with that of meropenem in hospitalized children 3 months to <18 years of age with cIAI (complicated intra-abdominal infection). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
•To determine the clinical cure rate of doripenem compared with that of meropenem at the TOC (test of cure) visit
•To determine the favorable microbiological response rate of doripenem compared with that of meropenem at the TOC visit
•To determine the clinical improvement rate of doripenem compared with that of meropenem at the end-of-treatment for IV study drug therapy (EIV) visit
•To determine the clinical cure rate of doripenem compared with that of meropenem at the late follow-up (LFU) visit
•To determine the favorable microbiological response rate of doripenem compared with that of meropenem at the LFU visit
•To characterize the pharmacokinetics of doripenem in hospitalized children with cIAI based on a sparse pharmacokinetic sampling scheme |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 - Subject randomly assigned to treatment postoperatively or intra-operatively after visual confirmation of established cIAI (presence of pus within the abdominal cavity) including the following eligible diagnoses:
– appendicitis complicated by rupture and/or abscess
– traumatic perforation of the intestines, which are being operated on more than 12 hours after perforation occurred
– acute gastric, duodenal, or gall bladder perforations, which are being operated on more than 24 hours after perforation occurred
– secondary peritonitis due to perforated viscus, postoperative or other focus of infection. (Subjects with inflammatory bowel disease or ischemic bowel disease are eligible to enroll provided there is bowel perforation)
– intra-abdominal bacterial abscess (including liver)
OR
Subject randomly assigned to treatment pre-operatively and has pre-operative clinical evidence of cIAI including all of the following:
– Evidence of systemic inflammatory response as demonstrated by at least one of the following:
Fever (oral temperature >38.0C, tympanic temperature >38.3C, or rectal or core temperature >38.8C) or hypothermia (rectal or core temperature <35.0C)
Have leukocytosis (WBC count ≥15,000 cells/µL OR ≥15% immature neutrophils , regardless of the total peripheral white cell count)
Hypotension defined by the following:
o For children greater than 1 year of age: Systolic blood pressure ≤70 mm Hg + (2 multiplied by age [in years])
o For children aged 3 months to ≤1 year: Systolic blood pressure ≤70 mm Hg
AND
– At least one of the following physical signs consistent with cIAI:
o Abdominal pain or tenderness
o Localized or diffused abdominal wall rigidity
o Presence of abdominal mass
o Ileus
AND
– Supportive radiologic findings in the abdomen such as intraperitoneal abscess detected on computer tomography scan films or an ultrasound;
2 - Must have a requirement for surgical intervention (eg, laparotomy, laparoscopic surgery, or percutaneous drainage) to manage the cIAI within the 24 hours before to within the 24 hours after randomization;
3 - 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 subject must require at least 3 days of IV antibiotic therapy initially). |
|
E.4 | Principal exclusion criteria |
1 - Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other β-lactam antibiotics. Note: Subjects with a history of mild non urticarial skin rash temporally related to but considered not associated with the previous use of β-lactam antibiotics are permitted to enroll in the study. For such subjects, there must be a description of the rash and documentation by the investigator that upon review of the history it is his/her opinion that the rash was unlikely due to any of the above-mentioned classes of drugs for the subject to qualify for inclusion in the study;
2 - Concomitant infection including but not limited to suspected or confirmed meningitis or other CNS infection requiring systemic antibiotic or antifungal therapy at the time of randomization. (Clarification: possible bacteremia with a presumed intra abdominal pathogen is acceptable);
3 - Have received more than 24 hours of systemic antibiotic therapy immediately preceding the start of the infusion of the first dose of IV study drug therapy
4 - Girls who are pregnant or are nursing a child or are menarchal, and if sexually active are not practicing a highly effective method of birth control (eg, prescription hormonal contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method, eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream or gel, male partner sterilization) as local regulations permit, before screening and do not agree to continue using a highly effective method of birth control (as previously described) for 30 days after administration of the last dose of study drug therapy. Note: for all menarchal girls, confirm a negative urine or serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) at screening, before enrolling the subject into the study;
5 - Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6 months before randomization. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The safety of doripenem compared with meropenem in children with cIAI will be evaluated by monitoring adverse events, changes in clinical laboratory tests, and findings from vital signs measurements and physical examinations. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety will be assessed during the 5 to 14 day treatment period and at posttreatment visits scheduled 7 to 14 days and 28 to 42 days, respectively, after the last dose of study drug. |
|
E.5.2 | Secondary end point(s) |
1 - Clinical cure rate and favorable per-patient microbiological response rate of doripenem compared with meropenem at test of cure (TOC) visit
2 - Clinical improvement of doripenem compared with meropenem at end of treatment (EIV) for iv study drug therapy
3 - Clinical cure rate and favorable per-patient microbiological response rate of doripenem compared with meropenem at late follow Up (LFU) visit
4 - Characterize pharmacokinetics of doripenem in hospitalized children with cIAI on the basis of a sparse pharmacokinetic sampling scheme |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - 7 to 14 days after the last dose of study drug
2 - Within 24 hours after completion of the last dose of iv study drug
3 - 28 to 42 days after the last dose of study drug
4 - 1, 2, 4 and 6 hours after the 4th, 5th, 6th, or 7th dose administrations of doripenem/doripenem placebo |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
Brazil |
Colombia |
India |
Latvia |
Lithuania |
Panama |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of trial is last visit of the last subject (Late Follow Up visit (LFU) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |