| 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 | 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 |
To show non-inferiority in the efficacy of FlutiForm pMDI 250/10 µg (2 puffs bid) vs Fluticasone pMDI 250 µg (2 puffs bid) plus Formoterol pMDI 12 µg (2 puffs bid) administered concurrently, based on the mean change in the pre morning dose value of forced expiratory volume in the first second (FEV1) from baseline (end of run-in period) to the end of the 8 week treatment period.
The co-primary endpoint of this study is:
To show non-inferiority in the efficacy of FlutiForm pMDI 250/10 μg (2 puffs bid) vs Fluticasone pMDI 250 μg (2 puffs bid) plus Formoterol pMDI 12 μg (2 puffs bid) administered concurrently, based on the mean change from the pre morning dose FEV1 value at baseline (end of run-in period) to the 2 hour post morning dose FEV1 value at the end of the 8 week treatment period. |
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| E.2.2 | Secondary objectives of the trial |
To show superiority in the efficacy of FlutiForm pMDI 250/10 µg (2 puffs bid) vs Fluticasone pMDI 250 µg (2 puffs bid) alone by means of 12 hour FEV1 AUC (in a subset of 47 subjects per treatment group).
To show superiority of FlutiForm pMDI 250/10 µg (2 puffs bid) vs Fluticasone pMDI 250 µg (2 puffs bid) alone in mean change of the pre morning dose FEV1 value from baseline (end of run-in period) to the end of the 8 week treatment period.
To show superiority of FlutiForm pMDI 250/10 µg (2 puffs bid) vs Fluticasone pMDI 250 µg (2 puffs bid) alone in mean change from the pre morning dose FEV1 value at baseline (end of run-in period) to the 2 hour post morning dose FEV1 value at the end of the 8 week treatment period.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female subjects at least 18 years old.
2. Females less than one year post-menopausal must have a negative urine pregnancy test recorded at the screening visit prior to the first dose of study medication, be non-lactating, and 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 severe persistent, reversible asthma for ≥ 6 months prior to the Screening Visit characterised by treatment with ICS at a dose of ≥ 500µg fluticasone or equivalent.
4. Demonstrated a FEV1 of ≥ 40% to ≤ 80% for predicted normal values (Quanjer et al., 1993) during the Screening Visit (Visit 1) and Randomisation Visit (Visit 3) following appropriate withholding of asthma medications (if applicable).
- No β2-agonist use on day of screening.
- No use of inhaled combination asthma therapy on day of screening.
- Inhaled corticosteroids are allowed on day of screening.
5. Documented reversibility of ≥ 15% in FEV1 in the screening phase.
6. Demonstrated satisfactory technique in the use of the study medication.
7. Willing and able to enter information in the electronic diary and attend all study visits.
8. Willing and able to substitute study medication for their pre study prescribed asthma medication for the duration of the study.
9. Written informed consent obtained.
Inclusion criteria required following run-in:
10. Subject has used rescue medication for at least 3 days and also had either at least one night with sleep disturbance (i.e., sleep disturbance score of ≥ 1) or at least 3 days with asthma symptoms (i.e., a symptom score of ≥ 1) during the last 7 days of the run-in period.
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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 the 4 weeks before the Screening Visit.
3. Known history of systemic (injectable or oral) corticosteroid medication within 1 month of the Screening Visit.
4. Known history of omalizumab use within the past 6 months.
5. Current evidence or known 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.
6. In the investigator’s opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the Screening Visit.
7. Significant, non-reversible, active pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, tuberculosis).
8. Known Human Immunodeficiency Virus (HIV)-positive status.
9. Subject has a smoking history equivalent to “10 pack years” (i.e., at least 1 pack of 20 cigarettes /day for 10 years or 10 packs/day for 1 year, etc.).
10. Current smoking history within 12 months prior to the Screening Visit.
11. Current evidence or known history of alcohol and/or substance abuse within 12 months prior to the Screening Visit.
12. Subject has taken β-blocking agents, tricyclic antidepressants, monoamine oxidase inhibitors, astemizole (Hismanal), quinidine type antiarrhythmics, or potent CYP 3A4 inhibitors such as ketoconazole within the past week.
13. Current use of medications other than those allowed in the protocol that will have an effect on bronchospasm and/or pulmonary function.
14. Current evidence or known history of hypersensitivity or idiosyncratic reaction to test medications or components.
15. Subject has received an investigational drug within 30 days of the Screening Visit (12 weeks if an oral or injectable steroid).
16. Subject is currently participating in a clinical study or has already received FLT3503 double-blind medication. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy variable will be the mean change in the pre morning dose FEV1 value from baseline (end of run-in period) to the end of the 8 week treatment period. The co-primary efficacy variable will be the mean change from the pre morning dose FEV1 value at baseline (end of run-in period) to the 2 hour post morning dose FEV1 value at the end of the 8 week treatment period. FEV1 will be recorded using a centralised spirometry system that has been maintained and volume calibrated daily according to the manufacturer’s guidance. Investigators will ensure that each subject uses the centralised spirometry system throughout
the course of their involvement in the study. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | 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 | No |
| 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 | 62 |
| 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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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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