| 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 | 8.1 |
| E.1.2 | Level | LLT |
| 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 |
1. To determine the efficacy of mometasone furoate/formoterol (MF/F) MDI 200/10 mcg BID compared with mometasone furoate (MF MDI 200 mcg BID), in order to assess the added benefit of formoterol (F MDI 10 mcg BID) to the combination.
2. To determine the efficiacy of MF/F MDI 200/10 mcg BID compared with F MDI 10 mcg BID, in order to assess the benefit of the steroid component of the combination. |
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| E.2.2 | Secondary objectives of the trial |
| To assess the efficacy of MF/F MDI 200/10 mcg BID compared with placebo as measured by the Asthma Quality of Life Questionnaire [AQLQ(S)] total score, the Asthma Control Questionnaire (ACQ) total score, and the proporation of nights with nocturnal awakenings due to asthma which require use of short-acting inhaled beta2-agonist (SABA) rescue medication. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•A subject must have been using a medium daily dose of ICS (either alone or in combination with a LABA) for at least 12 weeks and must have been on a stable regimen (daily dose unchanged) for at least 2 weeks prior to Screening. Medium daily doses of ICS are defined in the protocol.
•If, based upon the medical judgement of the Investigator, there is no inherent harm in changing a subject’s current asthma therapy, the subject (and parent/guardian, if appliable) must be willing to discontinue their prescribed ICS or ICS/LABA combination at the Screening Visit, and be transferred to open-label treatment with MF MDI 200 microgram BID for 2-3 weeks prior to the Baseline/Randomization Visit.
• To document the diagnosis of asthma and assure the subject's responsiveness to bronchodilators before randomization, one of the following methods can be used at the Screening Visit, Day -14, or thereafter, but prior to the Baseline Visit:
* The subject must demonstrate an increase in absolute FEV1 of at least 12% and at least 200 mL within 15 minutes after administration of four inhalations of albuterol/salbutamol (total dose of 360 to 400 micrograms) or of nebulised SABA (2.5 mg) if confirmed as standard office practice , OR.
* The subject must demonstrate a PEF variability of more that 20% expressed as a percentage of the best and lowest morning pre-bronchodilator PEF over at least one week, OR
* The subject must demonstrate a diurnal variation in PEF of more than 20% based on the difference between the pre-bronchodilator morning value and the post-bronchodilator value from the evening before, expressed as percentage of the mean daily PEF value.
•At the Screening Visit, the subject's FEV1 must be >=60% and <=90%predicted.
•At the baseline Visit, FEV1 must be >=60% and <=85% predicted when all restricted medications have been withheld for the appropriate intervals.
•Clinical laboratory tests conducted at the Screening Visit must be within norrmal limits or clinically acceptable to the investigator/sponsor. An ECG performed at the Screening Visit using a centralized transtelephonic technology must be clinically acceptable to the investigator. A chest X-ray performed at Screening Visit or within 12 months prior to the Screening Visit must be clinically acceptable to the investigator.
•A female subject of childbearing potential must be using a medically acceptable, adequate form of birth control, as defined in the protocol, and must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment.
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| E.4 | Principal exclusion criteria |
•A subject who demonstrates a change (increase or decrease) in absolute FEV1 of > 20% at any time from the Screening Visit up to and including the Baseline Visit.
•A subject who requires the use of >8 inhalations per day of SABA MDI or >=2 nebulized treatments per day of 2.5 mg SABA, on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit.
•A subject who experiences a decrease in AM or PM PEF below the Screening Period stability limit on any 2 consecutive days prior to randomization.
•A subject who experiences an occurence of any clinical deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA) as judged by the clinical investigator at any time from the Screening Visit up to and including the Baseline Visit.
•A subject who is a smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history of > 10 pack-years.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1. The AUC (0-12 hr) of the change from baseline to Week 12 in FEV1 for the comparison of MF/F vs MF. The average of the two pre-dose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit will be subtracted from each of the serial measurements over the 12-hour period. The AUC will be calculated based on these changes from baseline evaluations.
2. Time-to-first asthma exacerbation over the 26-week treatment period for the comparison of MF/F vs F. 'Asthma exacerbation' is defined in the protocol. |
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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 | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| With preceding 2- 3 week open label run-in period |
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| 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.8.4.1 | 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 | 50 |
| 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 subject is considered to have completed the study upon completion of the last protocol-specified contact (eg, visits or telephone contacts).
For those subjects, who do not complete the study, subject participation will be considered upon the completion of the last visit or contact (eg, phone contact with the investigator or qualified designee).
The overall study ends when the last remaining subject has completed or has been discontinued from the study.
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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 | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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