| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 the dose-related efficacy by evaluating morning lung function at the end of the dosing interval (AM pre-dose percent predicted forced expiratory volume in one second [FEV1]) after 12 weeks of treatment, of three doses (50 mcg, 100 mcg, and 200 mcg) of mometasone furoate (MF) metered dose inhaler (MDI) twice a day (BID) compared with placebo in children 5 to 11 years of age, inclusive, with persistent asthma. |
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| E.2.2 | Secondary objectives of the trial |
| (1) To demonstrate the dose-related efficacy of MF MDI BID in improving morning (AM) peak expiratory flow (PEF) when compared with placebo; (2) To assess the dose-related efficacy of MF MDI BID compared with placebo as measured by the Paediatric Asthma Quality of Life Questionnaire with standardised activities (PAQLQ[S]) score; (3) To compare the efficacy of MF MDI 50 mcg BID with that of MF dry powder inhaler (DPI) 100 mcg once a day (QD) in the evening (PM). |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects of any race and either sex and 5 to 11 years of age, inclusive, with a diagnosis of persistent asthma for at least 6 months duration will be eligible for Screening. Subjects must meet all of the inclusion criteria and none of the exclusion criteria to receive treatment assignment.
Other key inclusion criteria are as follows:
•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 parent(s)/guardian) must be willing to discontinue their prescribed asthma medication and be transferred to an open-label treatment with MF MDI 50 mcg BID, once all laboratory tests are reviewed, and to one of the study treatments at Baseline.
•At both the Screening and Baseline Visits, an FEV1 greater than or equal to 60% and less than or equal to 90% predicted when all restricted medications have been withheld for the appropriate intervals.
•A subject must have been treated with a low to 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 before Screening. Low and medium daily doses of ICS are defined as follows:
Inhaled corticosteroid Low Daily Dose (mcg) Medium Daily Dose
Beclomethasone dipropionate 100-200 >200-400
Budesonide 100-200 >200-400
Budesonide nebs 250-500 >500-1000
Flunisolide 500-750 750-1250
Fluticasone propionate 100-200 >200-500
Triamcinolone acetonide 400-800 >800-1200
Ciclesonide 80-160 >160-320
Mometasone furoate 100 200
a Dose delivery by method or modality other than those noted above must be equivalent.
•A subject must have a documented positive beta-2 reversibility test, obtained within the 12 months before the consent/assent form may be signed. Otherwise, to support the diagnosis of asthma and assure the subject's responsiveness to bronchodilators before randomization, the following method must be used at the Screening Visit or at any time prior to the Baseline Visit:
oThe subject must demonstrate an increase in absolute FEV1 of at least 12% within 30 minutes after administration of 200 mcg to 400 mcg (2 to 4 puffs) of albuterol/salbutamol from a primed MDI or of a nebulized short-acting beta-2 agonist (SABA [2.5 mg]), if confirmed as standard office practice.
•Ability to use a peak flow meter correctly and to perform spirometry and PEF measurements.
•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 prior to starting the run-in treatment.
•Demonstration of ability to use MDIs and DPIs correctly using protocol-defined procedures.
•Willingness of the subject (and the subject’s legal representative) to give written informed consent/assent and to adhere to dose and visit schedules |
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| E.4 | Principal exclusion criteria |
• A subject who demonstrates a decrease in absolute FEV1 of greater than 20% at any time from the Screening Visit up to and including the Baseline Visit.
• A subject who demonstrates <80% compliance with use of study medication during the 2-week Run-in Period. Compliance will be determined by the number of inhalations recorded by the dose counter at the Baseline Visit (Visit 2).
• A subject who requires the use of more than eight inhalations per day of SABA or two or more 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 has a decrease in AM or PM PEF below the Run-in Period stability limit on any 2 consecutive days prior to randomization. To determine the stability limit, the average AM and average PM PEF respective values from the preceding 7 days will be added, divided by the number of non-missing values, and multiplied by 0.70.
• A subject who has an occurrence of clinical deterioration of asthma 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 as judged by the clinical investigator at any time from the Screening Visit up to and including the Baseline Visit.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable is the change in percent predicted FEV1 from Baseline to Week 12 for the evaluation of the dose-related efficacy of MF MDI BID, assessing the comparison of MF MDI 50 mcg BID vs. Placebo, MF MDI 100 mcg BID vs. Placebo, and MF MDI 200 mcg BID vs. Placebo. The percent predicted FEV1 equals the subject's observed FEV1 divided by the subject's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, Baseline, weeks 2, 4, 6, 8, and 12.
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| E.5.2 | Secondary end point(s) |
The following additional secondary Efficacy Endpoints will be evaluated for the dose related efficacy of MF MDI BID, as described for the primary efficacy endpoint:
(1) Change from Baseline in AM PEF at the 12-week Endpoint (last week of Diary Data).
(2) Change from Baseline in Asthma Quality of Life Questionnaire with standardised activities (PAQLQ[S]) score at the 12-week Endpoint (last post-baseline observation carried forward).
(3) Compare the efficacy and safety of MF MDI 50 mcg BID to that of the MF dry powder inhaler (DPI) 100 mcg once a day (QD PM) for change from Baseline to 12 Weeks in percent predicted FEV1.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1) daily; (2) Baseline, weeks 4, 8, and 12; (3) Screening, Baseline, weeks 2, 4, 6, 8, and 12.
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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 | Yes |
| 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) | 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 | 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 44 |
| 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 | No |
| 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 |
| Serbia |
| Bulgaria |
| Colombia |
| Croatia |
| El Salvador |
| Estonia |
| Greece |
| Hungary |
| India |
| Latvia |
| Lithuania |
| Puerto Rico |
| Mexico |
| Poland |
| Romania |
| Russian Federation |
| South Africa |
| Switzerland |
| Turkey |
| Ukraine |
| United States |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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