The primary focus of the study is the evaluation of the safety of treatment with moxifloxacin in a pediatric population 3 months to \<18 years old. Approximately 450 pediatric subjects with a complicated intra-abdominal infection will be enrolled in the study and treated with either moxifloxacin intravenously and orally if switched to oral therapy or ertapenem (intravenously) and, if switched to oral therapy, amoxicillin/clavulanate.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
458
For subjects 12 to less than (\<) 18 years of age and weighing at least 45 kilograms (kg), the dose of moxifloxacin will be 400 milligrams (mg), once daily (OD). Subjects 12 to \< 18 years of age and weighing less than 45 kg, the dose of moxifloxacin will be 4 mg/kg twice daily (BID), every 12 hours (q12h), not exceeding 400 mg/day. Subjects 6 to \< 12 years of age the dose of moxifloxacin will be 4mg/kg, q12h, not exceeding 400 mg/day. Subjects 2 to less than 6 years of age the dose of moxifloxacin will be 5mg/kg, q12h, not exceeding 400 mg/day. Subjects 3 months to less than 2 years of age the dose of moxifloxacin will be 6mg/kg q12h IV, not exceeding 400 mg/day. Subjects who were switched from IV to PO therapy, 400 mg or 50 mg moxifloxacin tablets were provided.
For subjects 13 to \<18 years of age, the dosage of ertapenem was 1 gram (g) OD. For subjects 3 months to \< 13 years of age, the dosage was 15 mg/kg q12h not to exceed 1 g/day.
Unnamed facility
Number of Subjects With Adverse Events
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: All AEs and SAE were recorded from treatment start to test of cure visit; musculoskeletal AEs were recorded up to 1 year post-end of treatment (EOT) visit; subjects with musculoskeletal AEs 1 year after EOT were followed up to 5 years or until resolution.
Number of Subjects With Clinical Cardiac Adverse Events
Time frame: Clinical cardiac event related to QT interval were recorded from treatment start until day 3 of treatment. All other clinical cardiac events were recorded from treatment start to test of cure visit, up to day 56.
Number of Subjects With Musculoskeletal Adverse Events
Time frame: All AEs and SAE were recorded from treatment start to test of cure visit; musculoskeletal AEs were recorded up to 1 year post-end of treatment (EOT) visit; subjects with musculoskeletal AEs 1 year after EOT were followed up to 5 years or until resolution.
Incidence Rates of Musculoskeletal Adverse Events by Primary System Organ Class (SOC) and Preferred Term
Musculoskeletal adverse events were classified as following SOCs (preferred terms): "injury, poisoning and procedural complications" (forearm fracture, joint injury, ligament sprain, muscle strain) "musculoskeletal and connective tissue disorders" (arthralgia, joint swelling, musculoskeletal pain, myalgia). Incidence rates were reported as percentage of subjects categorized under preferred terms.
Time frame: All AEs and SAE were recorded from treatment start to test of cure visit; musculoskeletal AEs were recorded up to 1 year post-end of treatment (EOT) visit; subjects with musculoskeletal AEs 1 year after EOT were followed up to 5 years or until resolution.
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Subjects 2 years to \< 18 years of age who were switched from IV to PO therapy receive amoxicillin/clavulanate suspension. The dosage of clavulanate was 3.2 mg/kg q12h. (maximum dose of clavulanate was 125 mg q12h). The dosage of amoxicillin was 22.5 mg q12h (a maximum dose of 875 mg amoxicillin q12h must not be exceeded).
Sterile 0.9% sodium chloride solution intended for IV use was used as the placebo for IV moxifloxacin. Tablets containing inactive ingredients were used as the placebo for PO moxifloxacin 400 mg and 50 mg tablets.
Sterile 0.9% sodium chloride solution intended for IV use was used as the placebo for IV ertapenem.
Suspension containing inactive ingredients was used as the placebo for PO amoxicillin/clavulanate suspension.
San Diego, California, United States
Unnamed facility
Springfield, Massachusetts, United States
Hospital de Agudos "Dr. Carlos Bocalandro"
Tres de Febrero, Buenos Aires, Argentina
Unnamed facility
Pleven, Bulgaria
Unnamed facility
Plovdiv, Bulgaria
Unnamed facility
Rousse, Bulgaria
Unnamed facility
Sofia, Bulgaria
Unnamed facility
Stara Zagora, Bulgaria
Unnamed facility
Calgary, Alberta, Canada
Unnamed facility
Hamilton, Ontario, Canada
...and 29 more locations
Heart Rate Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3
"N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
Time frame: Baseline (Pre-dose), Day 1, Day 3
PR Interval Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3
The PR interval is defined as the period that extends from the onset of atrial depolarization (beginning of the P wave) until the onset of ventricular depolarization. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
Time frame: Baseline (Pre-dose), Day 1, Day 3
RR Interval Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3
The RR interval refers to the respective time interval in the Electrocardiogram. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
Time frame: Baseline (Pre-dose), Day 1, Day 3
QRS Interval Changes in Electrocardiogram (ECG) Profiles From Predose to Post-dose on Treatment Day 1 and Treatment Day 3
The QRS interval represents the time it takes for ventricular depolarization to occur. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
Time frame: Baseline (Pre-dose), Day 1, Day 3
QT Interval Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3
The QT interval is the period that extends from the beginning of ventricular depolarization until the end of ventricular repolarization. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
Time frame: Baseline (Pre-dose), Day 1, Day 3
Corrected QT (QTc) Interval Calculated (Calc) Bazett Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3
QTc interval Calc Bazett represent the interval corrected for heart rate (QTc) milliseconds (msec) which was calculated by Bazett's method. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
Time frame: Baseline (Pre-dose), Day 1, Day 3
Corrected QT (QTc) Interval Calculated (Calc) Fridericia Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3
QTc interval Calc Fridericia represent the interval corrected for heart rate (QTc) msec which was calculated by Fridericia's method. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
Time frame: Baseline (Pre-dose), Day 1, Day 3
Potentially Clinically Significant Electrocardiogram (ECG) QTc Interval Prolongation - by QTc Interval Calc Fridericia Correction on Treatment Day 1 and During Therapy Day 3
A significant QTc prolongation was considered when the QTc value was more than (\>) upper limit of normal (ULN) range or was prolonged for 30 msec or 60msec in comparison with the pre-treatment value measured on Day 1. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively. Percentage of subjects with potentially clinically significant ECG data was reported.
Time frame: Baseline (Pre-dose), Day 1, Day 3
Potentially Clinically Significant Electrocardiogram (ECG) QTc Interval Prolongation - by QTc Calc Bazett Correction on Treatment Day 1 and During Therapy Day 3
A significant QTc prolongation was considered when the QTc value was more than ULN range or was prolonged for 30 msec or 60msec in comparison with the pre-treatment value measured on Day 1. "N" signifies subjects who were evaluable for the specified parameter for each arm, respectively. Percentage of subjects with potentially clinically significant ECG data was reported.
Time frame: Baseline (Pre-dose), Day 1, Day 3
Clinical Response at Test-of-Cure (TOC) Visit
Clinical responses were graded as clinical cure, failure or indeterminate. 'Clinical cure' defined as a resolution or sufficient improvement of clinical signs and symptoms related to the infection; 'failure' defined as a reappearance of the signs and symptoms of the original infection, or wound infection requiring further systemic antimicrobial therapy; 'indeterminate' defined as those subjects in whom a clinical assessment was not possible to determine (due to early withdrawal from the study because of adverse events, protocol violation, withdrawn consent). Percentage of subjects with clinical response at TOC were reported.
Time frame: 28 to 42 days
Bacteriological Response at Test-of-Cure (TOC) Visit
Bacteriological responses were graded as presumed persistence, presumed eradication or indeterminate. 'Presumed persistence' was applicable for subjects judged to be clinical failures, and appropriate culture material is not available for evaluation; 'presumed eradication' defined as the absence of appropriate culture material for evaluation because the subject has clinically responded and invasive procedures are not warranted; índeterminate' was applicable when the bacteriological response to the study drug was not valid for any reason (eg, pre-treatment culture was negative or culture was not obtained when material was available and the subject was not judged a clinical failure). Percentage of subjects with bacteriological response at TOC were reported.
Time frame: 28 to 42 days
Clinical Response at Test-of-Cure (TOC) Visit in Subjects With Bacteriologically Confirmed Complicated Intra-abdominal Infection (cIAI)
Clinical responses were graded as clinical cure, failure or indeterminate. 'Clinical cure' defined as a resolution or sufficient improvement of clinical signs and symptoms related to the infection; 'failure' defined as a reappearance of the signs and symptoms of the original infection, or wound infection requiring further systemic antimicrobial therapy; 'indeterminate' defined as those subjects in whom a clinical assessment was not possible to determine (due to early withdrawal from the study because of adverse events, protocol violation, withdrawn consent). Percentage of subjects with clinical response at TOC were reported
Time frame: 28 to 42 days
Clinical Response at a 'During Therapy' Visit
Clinical responses during therapy visit were graded as clinical improvement, clinical failure, or indeterminate. Clinical improvement defined as a reduction in the severity and/or the number of signs and symptoms of infection; 'clinical failure' defined as a failure to respond or insufficient lessening of the signs and symptoms of infection requiring a modification or addition of antibacterial therapy. 'Indeterminate' defined as those subjects in whom a clinical assessment is not possible to determine (eg, due to early withdrawal from the study because of adverse events, protocol violation, withdrawn consent, receipt of an effective concomitant antibacterial for an indication other than the study indication and receipt of less than 3 full days of study drug, etc). Percentage of subjects with clinical response during therapy visit were reported.
Time frame: Day 3 to Day 5
Bacteriological Response at a 'During Therapy' Visit
Bacteriological response during therapy were graded as presumed persistence, presumed eradication, or indeterminate'Presumed persistence' is applicable for subjects judged to be clinical failures and appropriate culture material is not available for evaluation;'presumed eradication' is defined as the absence of appropriate culture material for evaluation because the subject has clinically responded (with a response as a resolution or cure) and invasive procedures are not warranted; 'indeterminate is applicable when the bacteriological response to the study drug is not valid for any reason (eg, pretreatment culture was negative or culture was not obtained when material was available and the subject is not judged a clinical failure). Percentage of subjects with bacteriological response during therapy visit were reported
Time frame: Day 3 to Day 5
Clinical Response at the End-of-Treatment (EOT) Visit
Clinical responses at EOT were graded as resolution, failure, or indeterminate. 'Resolution' defined as a disappearance of signs and symptoms related to the infection or sufficient improvement of clinical signs and symptoms related to the infection and the subject does not require any further antibiotic therapy or surgical intervention; 'failure' defined as worsening or insufficient lessening of the signs and symptoms of infection requiring a modification or addition of antibacterial therapy; 'indeterminate' is defined as those subjects in whom a clinical assessment is not possible to determine (eg, due to early withdrawal from the study because of adverse events, protocol violation, withdrawn consent; receipt of less than 3 full days of study drug; receipt of an effective concomitant antibacterial for an indication other than study indication; etc). Percentage of subjects with clinical response at EOT were reported.
Time frame: Day 5 to Day 14
Bacteriological Response at the End of Treatment (EOT) Visit
Bacteriological response at EOT were grades as presumed persistence, presumed eradication or indeterminate. 'presumed persistence' was applicable for subjects judged to be clinical failures and appropriate culture material is not available for evaluation; 'presumed eradication' defined as the absence of appropriate culture material for evaluation because the subject has clinically responded (with a response as a resolution or cure) and invasive procedures are not warranted; 'indeterminate' is applicable when the bacteriological response to the study drug was not valid for any reason (eg, pretreatment culture was negative or culture was not obtained when material was available and the subject was not judged a clinical failure). Percentage of subjects with bacteriological response at EOT were reported.
Time frame: Day 5 to Day 14