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 |
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. |
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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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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 prior to initiating MF MDI run-in medication. - A subject must have a history of ≥ 2 asthma-related unscheduled visits to either a physician or to an emergency room within the past year OR ≥3 asthma-related unscheduled visits within the past 2 years. NOTE: Documentation in the chart that a subject had a worsening in his/her asthma condition requiring a change in treatment without a visit to a physician or ER will also be accepted as an 'unscheduled visit'. - 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 approximately 15 to 20 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 mean 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 (before taking albuterol/salbutamol) morning value and the postbronchodilator value (after taking albuterol/salbutamol) from the evening before, expressed as a percentage of the mean daily PEF value on any day during the open-label Run in Period. NOTE: If a subject is to be qualified using diurnal variation, the subject should be instructed to perform his/her PEF evaluation after using his/her bronchodilator in the evening. - At the Screening and Baseline Visits, the subjects 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, including serum pregnancy for females of child-bearing potential, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor before the subject is instructed to start using open-label MF MDI run-in medication. - 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. In Germany, a chest x-ray will not be performed at Screening. Only subjects who have a historical chest x-ray result within the last 12 months will be permitted into the study. - 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 the MF MDI Run-in Period.
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E.4 | Principal exclusion criteria |
- A subject who experiences a decrease in AM or PM PEF below the Run-in 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 (including oral or other systemic corticosteroids but allowing SABA).
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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. |
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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) | 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 |
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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 | 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 | 6 |
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 |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |