E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic disease of the lungs characterized by airway inflammation, bonchoconstriction and increased airway responsiveness. |
|
E.1.1.1 | Medical condition in easily understood language |
Asthma: A medical condition where inflammation (redness and swelling) and constriction (tightening) of the airways is present in the lungs making it difficult to breath. |
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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 | 18.0 |
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 |
|
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 evaluate the effect of two weeks treatment with inhaled fluticasone furoate versus placebo once daily on short-term lower-leg growth using a knemometer. |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety of 50 mcg inhaled fluticasone furoate |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged 5 years to less than 12 years at Visit 1.
At least 15 (25%) children of the total study population must be aged 5 to less than 8 years.
2. Male or pre-menarchial female subjects.
3. Subjects must be pre-adolescent without any signs of puberty (Tanner Stage 1).
4. Normal range for their height and weight. Weight and height measurements should fall within the percentile range 3-97% of normal values for age according to Danish growth charts.
5. Have a documented diagnosis of persistent asthma, as defined by the National Institutes of Health (National Institutes of Health, 2007) for at least 3 months prior to the Screening Visit.
6. A pre-bronchodilatory FEV1 at Visit 1 (Screening) ≥ 80% predicted. There should be no SABA use within 4 hours of this measurement.
7. Using one of the following asthma therapies prior to entry into the study:
• Short acting beta-agonist (SABA) inhaler alone (e.g. salbutamol) on an as required basis and/or
• Regular non-ICS controller medications for asthma (e.g. cromones or leukotriene receptor antagonists) and/or
• Previously treated with ICS (equipotent to inhaled budesonide ≤ 400 mcg total daily dose).
There must be no ICS use within 2 weeks of Visit 1 (Screening).
8. Able to replace their current SABA treatment with study supplied rescue SABA provided at Visit 1 for use as needed for the duration of the study.
9. Written informed consent from at least one parent/care giver (legal guardian) and accompanying informed assent from the subject (where the subject is able to provide assent) prior to admission to the study.
• If applicable, subject must be able and willing to give assent to take part in the study according to the local requirement. The study investigator is accountable for determining a child's capacity to assent to participation in a research study, taking into consideration any standards set by the responsible IEC.
• Subject and their legal guardian(s) understand that the study requires them to be treated on an outpatient basis.
• Subject and their legal guardian(s) understand that they must comply with study medication and study assessments including recording of PEF and rescue SABA use, attending scheduled study visits, and being accessible by a telephone call |
|
E.4 | Principal exclusion criteria |
1. A history of life-threatening asthma defined for this protocol as an asthma episode that required intubation, hypercapnea requiring noninvasive ventilatory support, respiratory arrest, hypoxic seizures or asthma-related syncopal episode(s).
2. Subjects with a history of asthma exacerbation requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or a depot corticosteroid injection or ER attendance (within 3 months) or requiring hospitalization for asthma (within 6 months) prior to screening.
3. Significant, non-reversible active pulmonary disease (e.g. cystic fibrosis, bronchiectasis, tuberculosis).
4. Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
5. Any fracture in the leg to be measured within 6 months prior to the screening visit.
6. Any metabolic disorders or other diseases that may impact on normal growth patterns.
7. No major surgery requiring general anaesthesia for at least 3 months prior to the screening visit.
8. No febrile illnesses with temperature >39 degrees Celsius for more than five consecutive days within the week preceding the Screening Visit.
9. Any significant abnormality or medical condition identified at the screening medical assessment (including serious psychological disorder) that in the Investigator's opinion, preclude entry into the study due to risk to the subject or that may interfere with the outcome of the study.
10. Clinical visual evidence of candidiasis at Visit 1 (Screening).
11. Use of any of the prohibited medications listed in Section 6.11 of the protocol.
12. Strenuous physical exercise within 3 hours of Visit 1 (Screening)
13. Drug allergies: Any adverse reaction including immediate or delayed hypersensitivity to any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the ELLIPTA Inhaler (i.e., lactose, FF).
14. Milk Protein Allergy: History of severe milk protein allergy.
15. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
16. Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
17. Unable to use the ELLIPTA inhaler and peak flow meter correctly
19. The Parent or Guardian has a history of psychiatric disease, intellectual deficiency, substance abuse or other condition (e.g. inability to read, comprehend or write) which may affect:
• validity of consent to participate in the study
• adequate supervision of the subject during the study
• compliance of subject with study medication and study procedures (e.g.completion of daily diary, attending scheduled clinic visits)
• subject safety and well-being
20. Children in care: Children who are wards of the government or state are not eligible for participation in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean growth rate (mm/wk) in lower leg growth, as determined by
knemometry |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 15/visit 3 and Day 43/Visit 5 (end of treatment) |
|
E.5.2 | Secondary end point(s) |
Incidence of adverse events |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 end of the study is defined as the last subject's last visit. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 28 |