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 | 10000744 |
E.1.2 | Term | Acute exacerbation of chronic bronchitis NOS |
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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 |
To demonstrate the superioity of faropenem medoxomil versus placebo, in terms of clinical response, in the treatment of the subjectswith a microbiologically documented acute exacerbation of chronic bronchitis |
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E.2.2 | Secondary objectives of the trial |
Clinical response (as measured by clinical signs and symptoms) and sputum purulence at the During Therapy Visit (Day 2 to 5) will be compared between treatment groups in the clinically evaluable population; Clinical response at the TOC (Test-of-Cure) Visit in the Intent-to Treat (ITT) population; Clinical response at the Late Post-Therapy Follow-up Visit in the clinically evaluable population; Patient Reported Outcomes using a Clinical COPD Questionnaire at Visit 1 (Pre-Therapy), Visit 2 (During Therapy), Visit 3 TOC (Test-of-Cure) and Visit4 (Late Post-Therapy Follow-Up) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Male or non-pregnant female outpatients age ≥ 35 years with significant COPD (GOLD criteria I, II or III), chronic cough and sputum production and an acute exacerbation of chronic bronchitis; b. have a history (past or current) of smoking (≥ 10 pack-years); c. Have evidence of airflow obstruction (within a year prior to the current exacerbation or during the current exacerbation and then reconfirmed after recovery), defined as: - Forced expiratory volume in one second (FEV1) % predicted ≥ 35 years and - Ratio of FEV1 to forced capacity (FVC) of 0.70 d. Have a clinical diagnosis of AECF defined as: - Cough and sputum production on most days for at least 3 consecutivemonths for > 2 successive years - All of the following cardinal symptoms must be present: * Increase in or worsening of cough * Increase or worsening of dyspnea * Increase in sputum volume * Increase in sputum purulence e. Patient must provide a purulent or muco-purulent sputum by deep expectoration for culture and susceptibility testing on the day of study enrollment; f. If female, the subject must: - be postmenopausal for at least 1 year, OR - have had a bilateral oophorectomy and/or hysterectomy, OR - have had a bilateral tubal ligation or otherwise be incapable of pregnancy, OR g. if of childbearing potential, the subject must: - have maintained her normal menstrual pattern duting the 3 months prior to study entry, AND - have taken hormonal contraceptives for at least 1 month prior to study entry, or agree to use spermicide and barrier methods or have been using another acceptable method of contraception and agree to continue with the same method during the study, AND - have had a negative urine β- subunit hCG pregnancy test sensitive to at least 50 µU/mL of β-hCG immediately prior to study entry; h. female subjects who become pregnant during participation must be promptly withdrawn from the trial The subject is to be withdrawnfrom the study if the urine pregnancy test is positive; i. Read and sign the Informed Consent j. Subject is an appropriate candidate for oral antibacterial therapy
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E.4 | Principal exclusion criteria |
a. History of hypersensitivity to faropenem medoxomil or any of the components of the product or a history of an anaphylactic reaction to β-lactams (e.g., penicillins or cephalosporins); b. Chest x-ray or other radiographic documentation of an underlying pneumonia; c. Known lung or chest cavity malignancy active within the past 5 years; d. Known concurrent medically active conditions likely to interfere with the evaluation of efficacy (e.g., pulmonary tuberculosis, bronchiectasis, cystic fibrosis, etc.) e. Known neutropenia (< 1000 cells/mm3), or CD4 count of < 200 cells/mm3, or on highly active antiretroviral therapy (HAART). An HIV test is not required; f. The need for hospitalization or intravenous antibiotics for this exacerbation; g. Hospitalization for any cause within two weeks prior to study entry, lasting ≥ 48 hours; h. Any previous course of a systemic antibacterial agent within the last 2 weeks; i. Subject has severe renal insufficiency (CrCl < 30 mL/min) and/or severe hepatic insufficiency (Childs-Pugh Class C); j. Previous treatment under this Protocol; k. Subject is pregnant or breastfeeding; l. Receipt of any experimental drug or medical device within the previous 30 days (or are scheduled to receive any other experimental procedures during the study period); m. Employees and/or family members of the Investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center. Subjects will be enrolled before the results of clinical and microbiological laboratory results are available.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary analysis of efficacy is the comparison of the clinical response rates of faropenem medoxomil to placebo at the Test-of-Cure visit in the modified Intent-to-Treat population |
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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 | 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 | No |
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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 | 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
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For most individual subjects, the trial ends at the Late Post-Therapy Follow-up visit inquiring about interim SAE experiences. Thus, the trial end is the time when the last subject has completed the follow-up visit or the follow-up SAE query contact has been completed. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |