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 | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003555 |
E.1.2 | Term | Asthma bronchial |
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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 of this study is to demonstrate a dose-response relationship between high dose (250/10 µg, 2 puffs) and low dose (50/5 µg, 2 puffs) FlutiForm® by comparing the effects of each dose strength on bronchial hyperresponsiveness to inhaled adenosine 5’-monophosphate (AMP) challenge. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the study are to assess the effect of FlutiForm® pMDI on other measures of airway inflammation (exhaled nitric oxide (eNO) and percentage of eosinophils in induced sputum) and to compare bronchial hyperresponsiveness to AMP challenge for each FlutiForm® dose group with placebo. Additional secondary objectives are to measure lung function, amount of rescue medication use, asthma symptom scores, sleep disturbance due to asthma, asthma exacerbations, discontinuation due to lack of efficacy, and spontaneously reported adverse events.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects aged between 18 and 55 years inclusive. 2. Females less than one year post-menopausal must have a negative serum or urine pregnancy test recorded at the screening visit prior to the first dose of study medication in each treatment period, be non-lactating, and be willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasectomised partner. 3. Known history of mild to moderate asthma for ≥ 6 months prior to the screening visit. 4. Subject has not received systemic (injectable or oral) corticosteroid medication in the 12 weeks prior to the study screening visit. 5. Demonstrate a FEV1 of ≥ 60% predicted FEV1 (Quanjer et al, 1993) at the screening visit, following appropriate withholding of asthma medications (no long-acting β2-agonist or short-acting β2-agonist/anticholinergic use 12 hours and 6 hours prior to screening, respectively). 6. Demonstrate AMP challenge PC20FEV1 < 60 mg/mL, following appropriate withholding of asthma medication (no short-acting bronchodilator use 6 hours prior to the AMP challenge test at Visit 2). 7. Non-smoker for at least 12 months prior to study screening. Ex-smokers must have a smoking history equivalent to less than “10 pack years” (i.e. at least 1 pack of 20 cigarettes per day for 10 years or 10 packs per day for 1 year, etc.). 8. Demonstrate satisfactory technique in the use of the pMDI. 9. Willing and able to enter information in the diary and attend all study visits. 10. Willing and able to substitute study medication for their pre-study prescribed asthma medication for the duration of the study. 11. Written informed consent obtained.
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E.4 | Principal exclusion criteria |
1. Near fatal or life-threatening (including intubation) asthma within the past year. 2. Hospitalisation or an emergency visit for asthma within 4 weeks prior to the screening visit. 3. History of omalizumab use within the past 6 months. 4. Current evidence or history of any clinically significant disease or abnormality including uncontrolled coronary artery disease, congestive heart failure, myocardial infarction, or cardiac dysrhythmia. ‘Clinically significant’ is defined as any disease that, in the opinion of the Investigator, would put the subject at risk through study participation, or which would affect the outcome of the study. 5. In the investigator’s opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the screening visit. 6. Significant, non-reversible, active pulmonary disease (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, tuberculosis). 7. Known Human Immunodeficiency Virus (HIV)-positive status. 8. Current evidence or history of alcohol and/or substance abuse within 12 months prior to the screening visit. 9. Subjects who have taken -blocking agents, tricyclic antidepressants, monoamine oxidase inhibitors, astemizole (Hismanal), quinidine type antiarrhythmics, or potent CYP 3A4 inhibitors such as ketoconazole within one week prior to the screening visit. 10. History of leukotriene receptor antagonist use, e.g. montelukast, within one week prior to the screening visit. 11. Current use of medications other than those allowed in the protocol that will have an effect on bronchospasm and/or pulmonary function. 12. Anti-histamines within 2 weeks prior to the screening visit; non-steroidal anti-inflammatory drugs, oral decongestants, inhaled cromolyn sodium, nedocromil sodium within one week prior to the screening visit. 13. Current evidence or history of hypersensitivity or idiosyncratic reaction to test medications, rescue medication, or components. 14. Use of an investigational drug within 30 days prior to the screening visit (12 weeks if an oral or injectable steroid). 15. Current participation in a clinical study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is PC20FEV1 (AMP).
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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 | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 7 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |