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 |
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 | 14.1 |
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 determine the safety and tolerability following administration of fluticasone furoate
100 μg (via a novel dry powder inhaler) once daily for 14 days in 5–11 year-old subjects. |
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E.2.2 | Secondary objectives of the trial |
• To characterize the pharmacokinetics of fluticasone furoate 100 μg (via a novel dry
powder inhaler) once daily for 14 days in 5–11 year-old subjects.
• To determine the effects of administration of fluticasone furoate 100 μg (via a novel
dry powder inhaler) once daily for 14 days in 5–11 year-old subjects on serum
cortisol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and pre-menarchial female subjects aged 5–11 years on the last planned
treatment day are eligible for this study. Pre-menarchial females are defined as any
female who has yet to begin menses and is considered Tanner Stage 2 or less.
2. Diagnosis of asthma at least 6 months prior to screening.
3. Patients must be controlled on their existing asthma treatment at screening as defined
by a Childhood Asthma Control Test score of >19 and PEF ≥80% predicted.
4. Apart from asthma, eczema and rhinitis, subjects should be healthy and suffer from
no other significant medical conditions.
5. Subjects must be taking a stable regimen of a short acting beta-agonist inhaler on an
as-need basis for at least 4 weeks prior to screening.
6. Subjects must weigh at least 15 kg.
7. Subjects must demonstrate ability to accept and effectively use the fluticasone
furoate devices using the demonstration kits provided to the site.
8. Subjects and parents/guardians must be able to understand and comply with protocol
requirements, instructions and protocol-stated restrictions. Parents/guardians must
have the ability to read, write and record diary information collected throughout the
study. They must also have the ability to manage study drug administration and PEF
assessments.
9. A signed and dated written informed consent from at least one parent/guardian, and accompanying informed assent from the subject prior to admission to the study.
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E.4 | Principal exclusion criteria |
1. Subjects who have changed their asthma medication within 4 weeks of screening or
subjects currently being treated with inhaled corticosteroids or have received such
treatment within 4 weeks of screening. In addition, subjects currently receiving (or
have received within 4 weeks of screening) any of the following asthma therapies:
theophyllines, long-acting inhaled beta-agonists or oral beta-agonists.
2. Any medical condition or circumstance making the volunteer unsuitable for
participation in the study (e.g. history of life-threatening asthma).
3. Any clinically relevant abnormality identified on the screening medical assessment,
including asthma exacerbation requiring systemic corticosteroids (oral,
intramuscular, intravenous) or emergency room attendance within 3 months or
asthma exacerbation requiring hospitalization within 6 months prior to screening.
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 screening
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. Clinical visual evidence of oral candidiasis at screening.
6. Parent/guardian has history of psychiatric disease, intellectual deficiency, substance
abuse, or other condition (e.g., inability to read, comprehend and write) which will
limit the validity of consent to participate in this study.
7. Any adverse reaction including immediate or delayed hypersensitivity to any beta-2-
agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid
therapy.
8. Known or suspected sensitivity to the constituents of the novel dry powder inhaler
(i.e., lactose or magnesium stearate), for example, history of severe milk protein
allergy.
9. A subject will not be eligible for this study if he/she is an immediate family member
of the participating Investigator, sub-Investigator, study coordinator, or employee of
the participating Investigator.
10. Children who are wards of the state or government.
11. Evidence of clinically significant abnormality in the 12-lead ECG at screening, as
follows:
i. Ventricular rate <65 bpm or >115 bpm if aged 5–7 years.
ii. Ventricular rate <55 bpm or >110bpm if aged 8–11 years.
iii. PR interval >160 msec if aged 5–7 years.
iv. PR interval >170 msec if aged 8–11 years.
v. QRS >100 msec.
vi. Evidence of Mobitz II second degree or third degree AV block.
vii. Evidence of ≥2 unifocal ventricular ectopic beats, couplets,
bigeminy, trigeminy or multifocal premature ventricular
complexes on three ECG traces.
viii. QTcB >450 msec or an ECG that is not suitable for QT
measurements (e.g. poor defined termination of the T wave).
ix. Right or left complete bundle branch block.
x. Clinically significant conduction abnormalities (e.g. left bundle
branch block, Wolff-Parkinson-White syndrome).
xi. Clinically significant arrhythmias (e.g. atrial fibrillation, atrial
flutter, ventricular tachycardia).
xii. Non-sustained VT (3 or more consecutive ventricular beats greater
than 100 bpm). |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Adverse events.
•Clinical laboratory assessments (hematology, chemistry and urinalysis).
•Peak expiratory flow on Day 1 (0–2 h) and Day 14 (0–12 h).
•Systolic blood pressure (BP) and diastolic blood pressure.
•Heart rate.
•Electrocardiographic (ECG) parameters: QT duration corrected for heart rate by Fridericia’s formula (QTcF).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
•Adverse events from start of investigational product until follow up contact.
•Clinical laboratory assessments at screening and pre-dose on Day 14
•Peak expiratory flow at screening and on Day 1 and Day 14 in the clinic and on Days 1-13 at home
•Systolic and diastolic blood pressure at screening, Day 1 and Day 14
•Heart rate and ECG at screening, Day 1 and Day 14 |
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E.5.2 | Secondary end point(s) |
•Fluticasone furoate maximum observed concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments AUC(0-t), AUC(0-12) and time of occurrence of Cmax (tmax) on Day 14.
•Serum cortisol weighted mean (0–12 h) on Day 14.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Fluticasone Furoate on Day 14
•Serum cortisol on Day 14 |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 12 |