| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Persistent Allergic Asthma |
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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 | 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 characterize the dose response of mometasone furoate/formoterol fumarate (MF/F) using exhaled nitric oxide (eNO) as a surrogate of airway inflammation. |
|
| E.2.2 | Secondary objectives of the trial |
| To determine the effects of MF/F on asthma symptoms, peak expiratory flow (PEF), sputum eosinophil count and bronchial response to mannitol challenge. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. To document a diagnosis of asthma, historical reversibility defined as an increase in absolute FEV1 of ≥12% and ≥200 mL must have been performed within 12 months of Screening. For subjects without historical reversibility, one of the following methods can be used at the Screening Visit, or at anytime prior to the Baseline Visit:
a. The subject must demonstrate an increase in absolute FEV1 of at least 12% and a volume increase of at least 200 mL within 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
b. 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 prebronchodilator PEF over at least 1 week, OR
c. The subject must demonstrate a diurnal variation PEF of more than 20% based on the difference between the prebronchodilator (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. {The calculation formula: Diurnal PEF Variation = Absolute [(highest of 3 readings, PM Post-BD PEF from prior evening) - (highest of 3 readings, AM Pre-BD from morning value)]/[(highest PM Post-BD + highest AM Pre-BD)/2] * 100}
2. At the Screening and Baseline Visits, a subject must have persistent allergic asthma with an FEV1 >65% predicted.
3. A subject must be allergic to at least one common allergen (grasses, trees, weeds, house dust mites, molds, dog and cat) as demonstrated by clinical symptoms when exposed to the allergen(s), and by skin prick testing or a RAST class >1 (excluding mRAST) within 2 years of inclusion in the study.
4. 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/or parent/guardian) must agree to discontinue prescribed ICS, anticholinergics, leukotriene receptor inhibitors, and long-acting β2 agonists at the Screening Visit as per required washouts, and be transferred to treatment with SABA for relief for 2 weeks prior to the Baseline/Randomization Visit.
5. Clinical laboratory tests (complete blood count, blood chemistries, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator.
6. An electrocardiogram (ECG) performed at the Screening Visit or within 30 days prior to Screening Visit must be clinically acceptable to the investigator and have a QTc interval <440 msec for males and <450 msec for females.
7. At Screening or any time prior to Baseline, a subject must have an eNO level of >30 ppb at a flow rate of 50 mL/second.
8. At Screening or any time prior to Baseline, a subject must have a sputum eosinophil count >3% of total cell count.
9. A subject (and/or parent/guardian) must be willing to give written informed consent and able to adhere to dose and visit schedules. A subject 12 to 17 years of age must also provide written assent. In countries where local or national regulations only permit adult subjects to participate in clinical studies, adolescents, as defined by that country, will not be enrolled.
10. A nonpregnant female subject of childbearing potential must be using a medically acceptable, adequate form of birth control. This includes:
a) hormonal contraceptives as prescribed by a physician (oral combined, hormonal implant or transdermal hormonal contraceptives);
b) medically prescribed IUD; or depot injectable;
c) medically prescribed topically applied ie, transdermal contraceptive patch;
d) condom in combination with a spermicide (double-barrier method);
e) monogamous relationship with a male partner who has had a vasectomy.
11. The subject must have started this birth control method at least 3 months prior to Screening (with the exception of condom in combination with spermicide), and must agree to continue its use for the duration of the study. A female subject of childbearing potential who is not currently sexually active must agree and consent to using a double-barrier method should she become sexually active during the course of this study. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. A female subject of childbearing potential 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 |
1. A subject who has been on systemic glucocorticosteroids (intravenous, intra-articular, or intramuscular), oral or high potency topical steroids within 3 months prior to Screening.
2. A subject who has had an upper or lower respiratory tract infection within the 4 weeks prior to Screening.
3. A subject who demonstrates a decrease in absolute FEV1 of >20% at any time between the Screening and Baseline Visits.
4. A subject who requires the use of greater than eight inhalations per day of SABA MDI, or two or more nebulized treatments of 2.5 mg SABA, on any 2 consecutive days between the Screening and Baseline Visits.
5. 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 Baseline. At Visit 1, the Run-in Period stability limit for PEF will be established based on the subject's personal best. If the subject does not have a historical personal best, the historical PEF measurement will be the PEF predicted based on the subject's sex, age, and height. PEF value will then be multiplied by 0.70 to determine the stability limit.
6. A subject who experiences a clinical asthma exacerbation defined as a 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, between the Screening and Baseline Visits.
7. A subject who is unable to perform sputum induction after a maximum of two attempts.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the percent change from Baseline to Day 14 in eNO. |
|
| 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 | Information not present in EudraCT |
| 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) | 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 | Yes |
| 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.8.3 |
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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 11 |
| 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
|
| 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 | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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