Clinical Trial Results:
A randomized, double-blind, multicenter trial to evaluate the safety and efficacy of sequential (intravenous, oral) moxifloxacin versus comparator in pediatric subjects with complicated intra-abdominal infection
Summary
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EudraCT number |
2009-015578-37 |
Trial protocol |
DE ES LV LT CZ BE HU BG GR Outside EU/EEA |
Global end of trial date |
21 Jan 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
24 Jul 2016
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First version publication date |
22 Jul 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAY12-8039/11643
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01069900 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Jan 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Jan 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety of treatment with moxifloxacin (compared to the safety of intravenous (IV) ertapenem followed by per oral (PO) amoxicillin/clavulanate).
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Jul 2010
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
15 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Ukraine: 159
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Country: Number of subjects enrolled |
United States: 6
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Country: Number of subjects enrolled |
Bulgaria: 69
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Country: Number of subjects enrolled |
Canada: 16
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Country: Number of subjects enrolled |
Chile: 2
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Country: Number of subjects enrolled |
Czech Republic: 9
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Country: Number of subjects enrolled |
Germany: 8
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Country: Number of subjects enrolled |
Greece: 5
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Country: Number of subjects enrolled |
Hungary: 25
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Country: Number of subjects enrolled |
Latvia: 88
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Country: Number of subjects enrolled |
Lithuania: 25
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Country: Number of subjects enrolled |
Mexico: 27
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Country: Number of subjects enrolled |
Peru: 3
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Country: Number of subjects enrolled |
Romania: 26
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Country: Number of subjects enrolled |
Russian Federation: 10
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Worldwide total number of subjects |
478
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EEA total number of subjects |
255
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
1
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Children (2-11 years) |
177
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Adolescents (12-17 years) |
300
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at multicenter between 21 July 2010 (first subject first visit) to 21 January 2015 (last subject last visit). | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Overall 478 subjects were enrolled, 20 subjects had screening failures hence, 458 subjects were randomized to receive treatment. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Subject, Carer, Assessor | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Moxifloxacin (Avelox, BAY12-8039) | ||||||||||||||||||||||||||||||
Arm description |
Subjects randomized to the moxifloxacin arm of this study received intravenous moxifloxacin plus ertapenem placebo (0.9 % sodium chloride [NaCl solution]) for a minimum of 3 days and, if switched to oral treatment, PO moxifloxacin plus PO amoxicillin/clavulanate placebo. Total treatment duration is 5-14 days. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Moxifloxacin
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Investigational medicinal product code |
BAY12-8039
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Other name |
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Pharmaceutical forms |
Injection, Tablet
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Routes of administration |
Intravenous use, Oral use
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Dosage and administration details |
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.
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.
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Arm title
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Comparator Ertapenem | ||||||||||||||||||||||||||||||
Arm description |
Subjects randomized to the comparator arm of this study received intravenous ertapenem plus moxifloxacin placebo (0.9 % NaCl solution) for a minimum of 3 days and, if switched to oral treatment, amoxicillin/clavulanate as an oral suspension plus PO moxifloxacin placebo. Total treatment duration is 5-14 days. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ertapenem
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Investigational medicinal product code |
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Other name |
Invaz
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
For subjects 13 to <18 years of age, the dosage of ertapenem were 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.
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Investigational medicinal product name |
Clavulanate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension and solvent for suspension for injection
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects 2 years to < 18 years of age who were switched from IV to PO therapy receive clavulanate suspension. The dosage of clavulanate was 3.2 mg/kg q12h. (maximum dose of clavulanate was 125 mg q12h).
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Investigational medicinal product name |
Amoxicillin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension and solvent for suspension for injection
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects 2 years to < 18 years of age who were switched from IV to PO therapy receive amoxicillin suspension. The dosage of amoxicillin was 22.5 mg q12h (a maximum dose of 875 mg amoxicillin q12h must not be exceeded).
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline period included only the treated subjects. Due to screen failure, not all enrolled subjects were randomized and treated with study drugs. |
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Baseline characteristics reporting groups
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Reporting group title |
Moxifloxacin (Avelox, BAY12-8039)
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Reporting group description |
Subjects randomized to the moxifloxacin arm of this study received intravenous moxifloxacin plus ertapenem placebo (0.9 % sodium chloride [NaCl solution]) for a minimum of 3 days and, if switched to oral treatment, PO moxifloxacin plus PO amoxicillin/clavulanate placebo. Total treatment duration is 5-14 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Comparator Ertapenem
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Reporting group description |
Subjects randomized to the comparator arm of this study received intravenous ertapenem plus moxifloxacin placebo (0.9 % NaCl solution) for a minimum of 3 days and, if switched to oral treatment, amoxicillin/clavulanate as an oral suspension plus PO moxifloxacin placebo. Total treatment duration is 5-14 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects (N= 451) treated with at least one dose of study medication.
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End points reporting groups
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Reporting group title |
Moxifloxacin (Avelox, BAY12-8039)
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Reporting group description |
Subjects randomized to the moxifloxacin arm of this study received intravenous moxifloxacin plus ertapenem placebo (0.9 % sodium chloride [NaCl solution]) for a minimum of 3 days and, if switched to oral treatment, PO moxifloxacin plus PO amoxicillin/clavulanate placebo. Total treatment duration is 5-14 days. | ||
Reporting group title |
Comparator Ertapenem
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Reporting group description |
Subjects randomized to the comparator arm of this study received intravenous ertapenem plus moxifloxacin placebo (0.9 % NaCl solution) for a minimum of 3 days and, if switched to oral treatment, amoxicillin/clavulanate as an oral suspension plus PO moxifloxacin placebo. Total treatment duration is 5-14 days. | ||
Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects (N= 451) treated with at least one dose of study medication.
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End point title |
Number of Subjects With Adverse Events [1] | |||||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
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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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [2] - Safety analysis set [3] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Cardiac Adverse Events [4] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
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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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [5] - Safety analysis set [6] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Musculoskeletal Adverse Events [7] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
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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Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [8] - Safety analysis set [9] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
Incidence Rates of Musculoskeletal Adverse Events by Primary System Organ Class (SOC) and Preferred Term | ||||||||||||||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
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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Notes [10] - Safety analysis set [11] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
Heart Rate Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3 | ||||||||||||||||||||||||
End point description |
"N" signifies subjects who were evaluable for the specified parameter for each arm, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline (Pre-dose), Day 1, Day 3
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Notes [12] - Safety analysis set [13] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
PR Interval Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3 | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline (Pre-dose), Day 1, Day 3
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Notes [14] - Safety analysis set [15] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
RR Interval Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3 | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline (Pre-dose), Day 1, Day 3
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Notes [16] - Safety analysis set [17] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
QRS Interval Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3 | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline (Pre-dose), Day 1, Day 3
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Notes [18] - Safety analysis set [19] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
QT Interval Changes in Electrocardiogram (ECG) Profiles From Pre-dose to Post-dose on Treatment Day 1 and Treatment Day 3 | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline (Pre-dose), Day 1, Day 3
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Notes [20] - Safety analysis set [21] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
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 | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline (Pre-dose), Day 1, Day 3
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Notes [22] - Safety analysis set [23] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
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 | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline (Pre-dose), Day 1, Day 3
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Notes [24] - Safety analysis set [25] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
Potentially Clinically Significant Electrocardiogram (ECG) QTc Interval Prolongation - by QTc Interval Calc Fridericia Correction on Treatment Day 1 and During Therapy Day 3 | ||||||||||||||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline (pre-dose), Day 1, Day 3
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Notes [26] - Safety analysis set [27] - Safety analysis set |
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No statistical analyses for this end point |
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End point title |
Potentially Clinically Significant Electrocardiogram (ECG) QTc Interval Prolongation - by QTc Calc Bazett Correction on Treatment Day 1 and During Therapy Day 3 | ||||||||||||||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (pre-dose), Day 1, Day 3
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [28] - Safety analysis set [29] - Safety analysis set |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Clinical Response at Test-of-Cure (TOC) Visit | |||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
28 to 42 days
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [30] - Safety analysis set with subjects evaluable for this outcome [31] - Safety analysis set |
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Bacteriological Response at Test-of-Cure (TOC) Visit | |||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
28 to 42 days
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [32] - Safety analysis set with subjects evaluable for this outcome [33] - Safety analysis set with subjects evaluable for this outcome |
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Clinical Response at Test-of-Cure (TOC) Visit in Subjects With Bacteriologically Confirmed Complicated Intra-abdominal Infection (cIAI) | |||||||||||||||||||||
End point description |
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
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
28 to 42 days
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [34] - Safety analysis set with subjects evaluable for this outcome [35] - Safety analysis set with subjects evaluable for this outcome |
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Clinical Response at a ‘During Therapy’ Visit | |||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Day 3 to Day 5
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [36] - Safety analysis set with subjects evaluable for this outcome [37] - Safety analysis set with subjects evaluable for this outcome |
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Bacteriological Response at a ‘During Therapy’ Visit | |||||||||||||||||||||
End point description |
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, pre-treatment 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
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Day 3 to Day 5
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [38] - Safety analysis set with subjects evaluable for this outcome [39] - Safety analysis set with subjects evaluable for this outcome |
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Clinical Response at the End-of-Treatment (EOT) Visit | |||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Day 5 to Day 14
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [40] - Safety analysis set with subjects evaluable for this outcome [41] - Safety analysis set with subjects evaluable for this outcome |
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Bacteriological response at the End of Treatment (EOT) visit | |||||||||||||||||||||
End point description |
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, 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 EOT were reported.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Day 5 to Day 14
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [42] - Safety analysis set with subjects evaluable for this outcome [43] - Safety analysis set with subjects evaluable for this outcome |
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
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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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Comparator Ertapenem
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomized to the comparator arm of this study received intravenous ertapenem plus moxifloxacin placebo (0.9 % NaCl solution) for a minimum of 3 days and, if switched to oral treatment, amoxicillin/clavulanate as an oral suspension plus PO moxifloxacin placebo. Total treatment duration is 5-14 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Moxifloxacin (Avelox, BAY12-8039)
|
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Reporting group description |
Subjects randomized to the moxifloxacin arm of this study received intravenous moxifloxacin plus ertapenem placebo (0.9 % NaCl solution) for a minimum of 3 days and, if switched to oral treatment, PO moxifloxacin plus PO amoxicillin/clavulanate placebo. Total treatment duration is 5-14 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Feb 2010 |
1. The sample size was increased from 300 to 450 patients.
2. Stratification of subjects by age was added to the protocol which allows a statistical analysis by age group.
3. A yearly follow-up up to 5 years after EOT was added if a musculoskeletal event has not resolved by the 1-Year Follow-up visit. This extended follow-up should ensure that subjects with unresolved musculoskeletal AEs are followed until resolution of the AE.
4. The list of drugs that might induce QTc prolongation and are therefore not allowed to be co-administered with moxifloxacin was expanded.
5. ECG measurement and interpretation of the results are explained in more detail.
6. Several additional examples of musculoskeletal related adverse events suggested by the FDA were added to the protocol.
7. The consistency of the descriptions of the musculoskeletal clinical and questionnaire assessments at different time points was improved.
8. Text describing how AEs which occur within 7 days of the EOT visit will be assessed and documented was added to the protocol. |
||
30 Aug 2011 |
1. Inclusion and exclusion criteria changed.
2. Post-study therapy description amended.
3. Schedule of procedures amended to clarify procedures during Pre-treatment and During therapy periods of the study.
4. Various editorial changes, minor error correction and clarification were included in amendment 3, as well as revising the format for displaying the literature references. |
||
07 Aug 2012 |
1. Clarifications with regards to ECG recordings as well as use of prior and concomitant medication that may influence QT interval have been added.
2. Clarification on when a premature termination visit is required has been added.
3. The possibility to contact patients by phone in case the do not return for follow-up visits has been introduced.
4. Various editorial changes, minor error correction and clarification were included in amendment 4. |
||
29 Jan 2013 |
1. Clarifications were made regarding dosing for children 3 months to less than 2 years of age.
|
||
29 Jan 2013 |
1. Temporal artery was added as a method of body temperature measurement in addition to oral, rectal, and tympanic as this is commonly used in some countries.
2. The reporting period for adverse events (AEs, SAEs, including “Hy’s Law” cases, and deaths) was changed from 7 days following EOT to the TOC visit as agreed to with the European Medicines Agency in the pediatric investigational plan.
3. The definition of significant renal impairment was modified to be consistent with the definition used in IV ertapenem comparator studies.
4. Quinolones have been excluded from allowed pre- and perioperative antibiotic treatment within 12 months prior to study entry.
5. Examination of the Achilles and patellar tendons was added to the skilled musculoskeletal assessment as recommended by an external expert.
6. Specific time points for the measurement of vital signs were added as recommended by the FDA.
7. The wording of the skilled musculoskeletal assessment questionnaire procedure was modified to refer to the correct visit.
8. Documentation of treatment of musculoskeletal AEs was added to be consistent with the CRF. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |