| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
|
| 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 non-inferiority between mometasone furoate/formoterol fumarate (MF/F) MDI 200/10 mcg BID and fluticasone propionate/salmeterol (F/SC) dry powder inhaler (DPI) 250/50 mcg BID on the effect of lung function after 12 weeks of treatment, in subjects with persistent asthma requiring maintenance treatment on medium doses of inhaled glucocorticosteroids. |
|
| E.2.2 | Secondary objectives of the trial |
To assess overall safety, onset-of-action, and asthma control, between two
treatment groups: MF/F MDI 200/10 mcg BID and F/SC DPI (Diskus) 250/50 mcg BID. |
|
| 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 (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 total daily doses of ICS are defined in the protocol.
• If, based upon the medical judgment of the investigator, there is no inherent harm in changing the subject’s current asthma therapy, the subject (and subject’s legal representative, if applicable) must be willing to discontinue his/her prescribed ICS or ICS/LABA combination at the Screening Visit, and be transferred to open-label treatment with MF MDI 200 mcg BID for 2 to 4 weeks (run-in) prior to the Baseline/Randomization Visit.
• A subject must have a history of ≥2 asthma-related unscheduled visits to a physician or to an emergency room within the past year AND ≥3 asthma-related unscheduled visits within the past 2 years.
• To document the diagnosis of asthma and assure the subject's responsiveness to bronchodilators before randomization, one of the following methods can used at the Screening Visit, or at anytime prior to the Baseline Visit:
1. The subject must demonstrate an increase in absolute FEV1 of at least 12% and a volume increase of at least 200 mL within 15 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg) or of nebulized SABA (2.5 mg), if confirmed as standard office practice, OR
2. The subject must demonstrate a peak expiratory flow (PEF) variability of more than 20% expressed as a percentage of the highest and lowest morning pre-bronchodilator PEF over at least 1 week, OR
3. The subject must demonstrate a diurnal variation PEF of more than 20% based on the difference between the pre-bronchodilator morning value and the postbronchodilator value from the evening before, expressed as a percentage of the mean daily PEF value on any day during the open-label Run in Period.
• At the Screening and Baseline Visits, the subject’s FEV1 must be ≥60% and ≤90% of predicted when all restricted medications have been withheld for the appropriate intervals.
• Prior to randomization subjects must have used a total of 12 or more inhalations of SABA rescue medication during the last 10 days of run-in.
• Clinical laboratory tests (complete blood counts [CBC], blood chemistries, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor.
• An electrocardiogram (ECG) performed at the Screening Visit, using a centralized trans-telephonic technology, must be clinically acceptable to the investigator.
• A chest x-ray performed at the Screening Visit, or within 12 months prior to the Screening Visit, must be clinically acceptable to the investigator.
• A non-pregnant female subject of childbearing potential must be using a medically acceptable, adequate form of birth control, as defined in the protocol.
• A female subject of childbearing potential who is not currently sexually active must agree and consent to using medically acceptable birth control, should she become sexually active during the course of this study.
• A female subject of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment. |
|
| E.4 | Principal exclusion criteria |
• A subject who demonstrates a change (increase or decrease) in absolute FEV1 of >20% at any time between the Screening and Baseline Visits. Note: PFTs will be performed in the morning.
• A subject who requires the use of greater than 8 inhalations per day of SABA (short-acting beta-agonists) MDI, or 2 or more nebulized treatments per day of 2.5 mg SABA, on any 2 consecutive days between the Screening and Baseline Visits.
• 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. The average AM and average PM PEF respective values from the preceding 7 days are added, divided by the number of non-missing values, and multiplied by 0.70 to determine the stability limit.
• A subject who experiences a clinical asthma exacerbation: defined as a clinical deterioration of asthma, as judged by the clinical investigator between the Screening and Baseline Visits, that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (other
than SABA).
• A subject with a clinically significant condition or situation, other than the condition being studied which, in the opinion of the investigator, may interfere with the study evaluations or optimal participation in the study.
• A subject who is a smoker or ex-smoker and has smoked within the previous year or has a cumulative smoking history >10 pack-years or equivalent. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the AUC(0-12 hr) of the change from Baseline to
Week 12 in FEV1. 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.
The primary endpoint analysis will be performed when all when all randomized subjects have completed Phase 1 of treatment, ie, following completion of the first 12 weeks of randomized treatment. In addition, the safety data will be used to accrue additional subjects as part of the overall safety assessment and total exposure for the MF/F FDC product. There is no plan to stop or interrupt the study (assuming that no significant subject health-related issues arise) as a result of these analyses; subjects will continue to be treated through the time that these analyses are performed and for the remainder of the 52-week Treatment Period.
The results of this Phase 1 analysis, representing the final analysis of the primary endpoint, will be restricted to a small group of individuals responsible for health authority submission preparation and will not be disclosed to investigational or
sponsor personnel without a need to know. |
|
| 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) | 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 | Yes |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| 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 |
| multi-center, two-phase, evaluator-blind |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 116 |
| 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 |
|
| 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
|
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.
|
|
| 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 | 4 |
| 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 | 4 |
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