E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10003553 |
E.1.2 | Term | Asthma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 |
This randomised controlled trial will test the hypothesis that macrolides improve asthma control and reduce sputum neutrophil counts of smokers with chronic asthma.
Primary Morning Peak Expiratory Flow after 12 wks of treatment |
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E.2.2 | Secondary objectives of the trial |
Secondary end points: - Average of the last 7 days PEF measurements before each visit from the home recordings, with 3 being the minimum number of evaluable days. - spirometry - airway responsiveness to methacholine - asthma control score - cough score - sputum cell counts - diary symptom scores - Exhaled Nitric Oxide - exacerbation rates
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
1. Diagnosis of asthma: Typical symptoms [episodic wheezing, chest tightness and/or dyspnoea] And either reversible airflow obstruction (> 12% and 200 ml change in FEV1 with nebulised salbutamol 2.5 mg) at any study visit prior to randomisation or methacholine airway hyperresponsiveness [20% drop in FEV1 at a concentration of methacholine ≤ 8 mg/ml]. 2. Age range 18-70 years [subjects above the age of 60 should have had asthma symptoms starting before the age of 40] 3. Duration of asthma symptoms > 1 year and on stable medication for 4 weeks 4. Able to maintain asthma without exacerbations at BTS step 2 level (beclometasone dose of 400 mcg/day and salbutamol as required) during the run-in period of the study. 5. Able to wean off other asthma medication, other than inhaled corticosteroid and short acting bronchodilator in the two weeks prior to the screening visit.
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E.4 | Principal exclusion criteria |
Exclusion criteria 1. Ex-smokers or never smokers 2. Planning to quit smoking during duration of trial 3. Patients with unstable asthma; defined as the presence of 1 or more of the following events in the month prior to randomisation [Emergency/’out of hours’ visit of patients to the GP; GP visit to patient at home; A & E hospital attendance; hospital admission]. 4. Patients with current epilepsy, psychosis or history of significant atrial or ventricular tachyarrhythmia. 5. Corrected QT-interval greater than 450 msec in women and greater than 430 msec in men on baseline electrocardiogram (ECG). 6. Low potassium levels [less than normal values for the laboratory]. If low potassium can be corrected, screening can continue with confirmation of normal levels prior to taking study medication. 7. Liver disease (alanine transaminase and/or aspartate transaminase levels 2 or more times the upper limit of normal). 8. Significant renal disease: creatinine or urea levels 2 or more times the upper limit of normal. 9. Any previous severe adverse reaction to macrolides. 10. Patients who are known to have specific IgE sensitivity or skin test positivity to grass pollen allergen and a history of worsening of asthma due to hay fever, will not be recruited from mid May to the end of July (grass allergen season in UK). 11. Upper or lower respiratory tract infection in the 4 weeks prior to randomisation. Run-in period can be prolonged in this situation to have 4 weeks with no respiratory infection prior to randomisation. 12. Patients who require medications known to interact with azithromycin including: - anti-psychotics, including Reboxitine and Quetiapine - antivirals, including Nelfinavir, Zidovudine, Didanosine - bromocriptine - carbergoline - clozapine - coumarin-Type Oral Anticoagulants including warfarin - cyclosporin - ergot derivatives - itraconazole - midazolam - mizolastine - moxifloxacin - rifamycins - theophylline - vinblastine
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in morning peak expiratory flow (PEF) |
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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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 study ends when the last patient has performed the last study visit.
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |