| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Complicated intra-abdominal infections (cIAI) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Complicated infection of the abdominal cavity |
|
| 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 | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10056570 |
| E.1.2 | Term | Intra-abdominal infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 |
| To evaluate the safety of treatment with moxifloxacin (compared to the safety of IV ertapenem followed by PO amoxicillin/clavulanate) |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives:
• To evaluate musculoskeletal adverse events (arthropathy, arthritis, tendinopathy, tendon rupture, musculoskeletal pain, gait abnormality, etc)
• To evaluate electrocardiogram (ECG) profiles obtained on Day 1 and Day 3 pre-treatment and post- treatment (serum peak level)
• To evaluate the clinical and bacteriological response at the Test-of-Cure (TOC) visit
• To evaluate the clinical response at the TOC visit among subjects with a bacteriologically confirmed complicated intra-abdominal infection (cIAI)
• To evaluate the clinical and bacteriological response to treatment at a “during therapy” visit (Day 3-5)
• To evaluate the clinical and bacteriological response to treatment at the End-of-Treatment (EOT) visit |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Hospitalized males or females 3 months to less than 18 years of age.
2. Able to obtain parental or legal guardian written informed consent and assent from subjects as applicable by local laws and regulations.
3. Expected duration of treatment with antibiotics is a minimum of 3 days administered IV, for a total of 5 to 14 days administered IV or IV followed by PO.
4. If the subject is a female of child bearing potential she must have a negative pregnancy test at the screening visit, be capable of practicing one of the following methods of contraception, and agree to continue the same method for 1 month following the TOC visit: Oral contraceptive at a stable dose for one menstrual cycle prior to the start of the study, contraceptive implant inserted at least one month prior to the start of the study, or contraceptive injection administered one month prior to the start of the study; intrauterine device; barrier method plus spermicide; spousal/partner sterility; or abstinence. Subjects taking oral contraceptives should additionally use barrier contraception plus spermicide or abstinence during study drug exposure. Lactating subjects are not to be included.
5. Subjects may be enrolled upon a surgically (laparotomy, laparoscopy, or percutaneous drainage) confirmed cIAI revealing at least one of the following:
• Gross peritoneal inflammation with purulent exudate within the abdominal cavity, and/or
• Intra-abdominal abscess, and/or
• Macroscopic intestinal perforation with diffuse peritonitis
OR
Subjects may be enrolled on the basis of a suspected cIAI, which must be supported with radiological evidence (ultrasound, abdominal plain films, computed tomography [CT], magnetic resonance imaging [MRI]) of gastrointestinal perforation or localized collections of potentially infected material
AND
At least one of the following:
• Symptoms referable to the abdominal cavity (eg, anorexia, nausea, vomiting or pain)
• Tenderness (with or without rebound), involuntary guarding, absent or diminished bowel sounds, or abdominal wall rigidity
• Fever (body temperature >38.0°C (100.4°F) oral; >38.5°C (101.3°F) rectal, tympanic membrane, or temporal artery) (as of Amd 2)
• Leukocytosis (white blood cells [WBC] ³ 12,000 cells/mm³)
AND
The subject must be scheduled for a surgical procedure (laparotomy or laparoscopy) or percutaneous drainage |
|
| E.4 | Principal exclusion criteria |
1. Presumed spontaneous bacterial peritonitis
2. All pancreatic processes including pancreatic sepsis, peripancreatic sepsis, or an cIAI secondary to pancreatitis
3. Early acute or suppurative (nonperforated) appendicitis unless there is evidence of an abscess or peritoneal fluid containing pus and micro organisms suggestive of regional contamination
4. Infections originating from the female genital tract
5. Known severe immunosuppression (eg, known neutropenia with absolute neutrophil count < 1000/mm³ caused by immunosuppressant therapy or malignancy, known lymphopenia with absolute CD4 + T-cell count < 200/mm³, presenting with an Acquired Immunodeficiency Syndrome [AIDS]-defining event and/or concomitant antiretroviral therapy [Note: Human immuno-deficiency virus {HIV} testing is not required for this study protocol], chronic treatment [>= 2 weeks] with known immunosuppressive therapy [including treatment with systemic prednisone or equivalent] or any other congenital or acquired immune defect or immunosuppression)
Subjects with known mild immunosuppression (eg, Type I or II diabetes mellitus, trauma, or absolute neutrophil count [ANC] between 1000 and 1500 cells/mm³) may be enrolled.
6. Subjects 1 year to less than 18 years of age need to have at least 80% of lower limit of normal (LLN) estimated glomerular filtration rate (eGFR) appropriate for age;
subjects 3 months to less than 1 year of age need to have at least 100% of LLN eGFR appropriate for age
7. History of tendon disease/disorder related to quinolone treatment
8. History of myasthenia gravis
9. Prior quinolone use within the previous 12 months
10. Systemic antibacterial treatment within the previous 7 days (a maximum of 24 hours of empiric pre- and perioperative antibiotic treatment [other than study drug] is allowed before start of study drug with the exception of quinolones)
11. Abnormal musculoskeletal findings at baseline assessment; or chronic musculoskeletal disease (eg, juvenile idiopathic arthritis); or chronic illness with high risk for chronic or recurrent arthritis or tendonitis (eg, bone or cartilage defects, juvenile idiopathic arthritis, systemic lupus erythematosus, vasculitides, dermatomyositis, Osgood Schlatter’s disease, retropatellar sydrome, fibromyalgia, cystic fibrosis, cerebral palsy, psoriasis, and chronic inflammatory bowel disease such as Crohn’s disease and ulcerative colitis)
12. Septic shock or suspected septic shock (as of Amd 2)
13. Psychotic subjects or subjects with a history of psychiatric diseases
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary variable will be safety with a special focus on cardiac and musculoskeletal events. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Safety will be assessed the whole time while the patient is enrolled in the study (pre-treament visit, treatement day 1, during therapy visit, switch from IV to PO visit (if applicable), EOT visit, TOC visit, 3 months and 1 year follow-up visits) |
|
| E.5.2 | Secondary end point(s) |
• To evaluate musculoskeletal adverse events (arthropathy, arthritis, tendinopathy, tendon rupture, musculoskeletal pain, gait abnormality, etc)
• To evaluate electrocardiogram (ECG) profiles obtained pre- and post-treatment on Day 1 and Day 3 pre-treatment and post-treatment (serum peak level)
• To evaluate the clinical and bacteriological response at the Test-of-Cure (TOC) visit
• To evaluate the clinical response at the TOC visit among subjects with a bacteriologically confirmed cIAI
• To evaluate the clinical and bacteriological response to treatment at a “during therapy” visit (Day 3-5)
• To evaluate the clinical and bacteriological response to treatment at the End of Treatment (EOT) visit |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Musculoskeletal adverse events will be recorded throughout the study until the 1 year follow-up visit. Study specific musculoskeletal assessments will be done on the pre-treatment visit, on the during therapy visit, on the EOT visit, the TOC visit and the 3 months and 1 year follow-up visits.
ECGs will be recorded on treatment day 1 and 3 pre- and post dose.
Clinical and bacteriological response will be evaluated at a during therapy visit as well as at EOT and TOC visit.
|
|
| 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 | Yes |
| 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 | No |
| 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 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Canada |
| Greece |
| Romania |
| Argentina |
| Brazil |
| Chile |
| Czech Republic |
| Germany |
| Hungary |
| Latvia |
| Lithuania |
| Spain |
| Mexico |
| Peru |
| Russian Federation |
| Ukraine |
| 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
|
| Last patient last visit (1 year post end of treatment) [Musculoskeletal AEs that have not resolved until the 12 months after the end of treatment visit, will require yearly evaluations until resolution or for up to 5 years, whichever occurs first] |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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