E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute exacerbation of chronic bronchitis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000743 |
E.1.2 | Term | Acute exacerbation of chronic bronchitis |
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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 is to compare the efficacy of moxifloxacin 400 mg PO OD for five days with the respective efficacy of amoxicillin clavulanic acid 875/125 mg PO BID for seven days in the treatment of subjects with AECB. The primary efficacy endpoint will be clinical failure rates at 8 weeks post-therapy visit in outpatients with AECB. Clinical failure is defined as the requirement for additional (including increased dose or duration of treatment) systemic antibiotics and/or systemic corticosteroids and/or hospitalization with antibiotic and/or systemic corticosteroid administration within 8 weeks post therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives will compare the following between the two treatment groups: •Clinical efficacy rates •Bacteriological eradication rates •Clinical efficacy rates (for subjects with positive sputum culture at enrollment) •Weekly mean symptom scores measured by the AECB-Symptom Scale (AECB-SS) •Rates and speed of symptom relief measured by the AECB-SS •Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators •Improvement in symptom burden measured by the AECB-SS •Improvement in health-related QoL measured by The St. George’s Hospital Respiratory Questionnaire (SGRQ) •Lung function test will be compared between treatment groups at each assessment visit •Healthcare resource utilization/consumption related to chronic bronchitis management •Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Outpatients 2.Male or female subjects, greater than or equal to 60 years old 3.Subject who can be managed with oral antimicrobials 4.FEV1≤50% predicted at enrollment in addition to a historical record of FEV1 of ≤60% within the past 12 months obtained during a stable infection-free period. A historical record of FEV1 is not required if the enrollment FEV1 is less than or equal to 50%. 5.Documented history of 2 or more AECB episodes, within 12 months of study enrollment, requiring a course of systemic antibiotics and/or systemic corticosteroids 6.All symptoms/signs must be present and confirmed by the Investigator: •Increase in dyspnea •Purulent sputum •Increase in sputum volume 7.Subject must provide a purulent sputum sample by deep expectoration prior to randomization for Gram stain, culture and sensitivity testing. The sputum will be assessed macroscopically by the investigator and graded according to the provided color chart. 8.Current or past cigarette smoker with great than or equal to 20 pack year smoking history 9.Subjects must have an infection free interval of at least 30 days prior to enrollment 10.Subjects must be willing and able to complete the questionnaires and subject booklet without assistance 11.Subjects with medical conditions and social status at the time of enrollment compatible with study protocol procedures 12.Willing and able to provide written informed consent |
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E.4 | Principal exclusion criteria |
1.Known hypersensitivity to quinolones, ß-lactams, or to any of the excipients of the study drugs 2.Known to have congenital or acquired QT prolongation 3.Known to have clinically relevant bradycardia 4.Known to have clinically relevant heart failure with reduced left ventricular ejection fraction 5.Known to have previous history of symptomatic arrhythmias 6.Taking QT prolonging drugs, for example class IA or III antiarrhythmic agents (e.g., quinidine, procainamide, amiodarone, sotalol), neuroleptics (e.g., phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressants, certain antihistaminics (e.g., terfenadine, astemizole, mizolastine), or other QT prolonging drugs (e.g., cisapride, vincamine iv, bepridil, and diphemanil) 7.Known electrolyte disturbances that are not controlled, particularly uncorrected hypokalemia 8.Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose galactose malabsorption 9.Requiring hemodialysis 10.History of a tendon disease/disorder 11.Known history of liver dysfunction, including known elevated transaminases (ALT and/or AST greater than 3 times the upper limit of normal) 12.Known severe renal impairment with glomerular filtration rate of <30mL/min 13.Known neutropenia (neutrophil count <1000/mm3) caused by immunosuppressive therapy or malignancy 14.Known to have AIDS (CD4 count of <200/mm3), or be HIV positive and receiving Highly Active Anti Retroviral Therapy (HAART) (HIV testing is not mandatory) 15.Known bronchial carcinoma, active pulmonary tuberculosis, known diffuse bronchiectasis, cystic fibrosis, chronic asthma (>15% reversibility), or pneumonia (a chest X-ray is not mandatory) 16.Known history of chronic colonization of pathogenic organisms resistant to moxifloxacin and/or amoxicillin clavulanic acid (e.g., Pseudomonas aeruginosa, MRSA) 17.Receiving long term (>4 consecutive weeks) systemic corticosteroid treatment (>10 mg/day of prednisolone or equivalent) 18.Received short course of systemic corticosteroid treatment within 30 days prior to enrollment 19.Requiring intravenous antibiotic therapy for treatment of the current exacerbation 20.Unable to take oral medication 21.Life expectancy of less than 6 months 22.Receiving systemic antibacterial therapy within 30 days prior to study enrollment 23.Requiring concomitant systemic antibacterial agents 24.Use of any investigational drug or device within 30 days of screening, or previously enrolled in this study 25.Requiring home ventilatory support (subjects requiring home/portable oxygen therapy or CPAP for sleep apnea are not excluded) and/or those who have a tracheotomy in situ |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy criterion are clinical failure rates at the follow-up visit 8 weeks after end of treatement. Clinical failure is defined as the requirement for additional (including increased dose or duration of tretment) systemic antibiotics and/or systemic steroids and/or hospitalisation for any respiratory events within 8 weeks post-therapy. Clinical and bacteriological outcome at the primary endpoint, 8 weeks after end of treatment, will be investigated in subpopulations of special interest, such as elderly subjects (65 years of age or older), subjects with at least 4 previous AECB episodes in the last 12 months, subject with cardiopulmonary disease, subjects with FEV1 at enrollment according to GOLD criteria (FEV1 less than 30% of predicted, between 30% and 60% or predicted, and 60% of predicted or greater). |
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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 | No |
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 109 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
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The end of study is defined as clean database. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |