| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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. |
|
| 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 | 17.0 |
| 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 safety and tolerability of inhaled FF/VI 100/25mcg
administered once daily in the morning for 14 days via a novel dry powder inhaler in subjects aged 5 to 11 years |
|
| E.2.2 | Secondary objectives of the trial |
• To characterise the pharmacokinetics of FF and VI following
administration as combination via a novel dry powder inhaler, once-daily for 14 days in subjects aged 5 to 11 years.
• To compare the systemic pharmacodynamic effects of administration
of FF and FF/VI via a novel dry powder inhaler, once-daily for 14 days on
glucose, potassium and cortisol in subjects aged 5 to 11 years. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the
following criteria apply:
1. Healthy as determined by a study physician, based medical history,
physical examination, laboratory testing, and ECG; with no significant medical condition apart from asthma, eczema, or rhinitis. A subject with a clinical abnormality or laboratory parameters outside the reference range for this study may be included if the Investigator and GSK Medical Monitor agree the finding is unlikely to introduce
additional risk factors or interfere with the study procedures.
2. Male and pre-menarchial female subjects aged 5 to less than 12
years on the last planned treatment day are eligible for this study. Pre-menarchial females are defined as any female who has not begun menses and is considered Tanner Stage 2 or less.
3. Diagnosis of asthma at least 6 months prior to screening.
4. Stable asthma therapy (fluticasone propionate, total daily dose less
than or equal to 400 mcg or equivalent) and short acting beta-agonist
(SABA) inhaler for at least 4 weeks prior to screening.
5. Subjects must be controlled on their existing asthma treatment at
screening, which will be continued during the run-in, washout and runout periods (but not during 25 active treatment periods). Control is defined as a Childhood Asthma Control Test score of >19 and PEF ≥ 75% predicted.
6. Subjects must demonstrate an ability to accept and effectively use a
demonstration inhaler from the demonstration kits provided.
7. Subjects must weigh at least 20 kg.
8. The subject and parent/guardian are able to understand and comply
with protocol requirements, instructions, and protocol stated restrictions. The parent or guardian must have the ability to read, write, and record diary information collected throughout the study. The parent or guardian must have the ability to manage study drug administration and PEF assessments.
9. At least one parent/guardian has signed and dated the written
informed consent prior to admission to the study. This will be accompanied by informed assent from the subject for children aged 7 to 11 years. |
|
| E.4 | Principal exclusion criteria |
1.Subjects with a history of life-threatening asthma, an asthma
exacerbation requiring systemic corticosteroids or ER attendance (within 3 months) or requiring hospitalization (within 6 months) prior to screening.
2. Subjects with any medical condition or circumstance making the
volunteer unsuitable for participation in the study.
3. Culture-documented or suspected bacterial or viral infection of the
upper or lower respiratory tract, sinus, or middle ear, not resolved
within 4 weeks of screening leading to a change in asthma management; or, in the opinion of the investigator, is likely to affect the subject's asthma status or ability to participate in the study.
4. Clinical visual evidence of oral candidiasis at screening.
5. Subjects currently receiving (or have received within 4 weeks of
screening) asthma therapies including theophyllines, long-acting inhaled beta-agonists, oral beta-agonists, or who have changed their asthma medication within 4 weeks of screening.
6. Significant abnormality of rate, interval, conduction or rhythm in the
12-lead ECG, determined by the investigator in conjunction with the age and gender of the child and the assessment provided by the remote analysis service.
7. QTcF > 450 msec or an ECG not suitable for QT measurement (e.g.
poorly defined termination of the T wave).
8. AST, ALT, alkaline phosphatase and bilirubin > 1.5xULN (isolated
bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
9. A known or suspected sensitivity to any constituents of the novel dry
powder inhaler (i.e. lactose or magnesium stearate) (e.g. history of severe milk protein allergy)
10. Any adverse reaction including immediate or delayed
hypersensitivity to any beta-2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy.
11. Use of prescription or non-prescription drugs, including vitamins,
herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
12. Consumption of red wine, seville oranges, grapefruit or grapefruit
juice, and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
13. The subject has participated in a clinical trial and has received an
investigational product within 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
14. Exposure to more than four new chemical entities within 12 months
prior to the first dosing day.
15. Where participation in the study would result in donation of blood
or blood products in excess of the lesser of 50mL or 3mL per kilogram within a 56 day period.
16. Parent/guardian has a 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.
17. Unwillingness or inability of the subject or parent/guardian to
follow the procedures outlined in the protocol.
18. Subject who is mentally or legally incapacitated.
19. Children who are wards of the state or government.
20. A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Assessment of safety and tolerability, including:
• Adverse events
• Clinical laboratory measurements
• Lung function (peak expiratory flow rate) on Day 1 (0-2 hr) and Day
14 (0-12 hr).
• Heart rate, including:
• Day 1 maximum 0-2 hr
• Day 14 maximum 0-2 hr
• Systolic and diastolic blood pressure 0-8 hr
• Electrocardiographic (ECG) parameters, including QT duration
corrected for Fredrica's formula (QTcF):
• Day 1 maximum QTcF 0-2 hr
• Day 14 maximum QTcF 0-2 hr |
|
| 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 on Day 14
•Peak expiratory flow at screening, on Day 1 and 14 in the clinic and
Days 2-13 at home
•Maximum heart rate and blood pressure at screening and Day 1 and
14
•Blood pressure at screening and on Day 1 and 14 in the clinic |
|
| E.5.2 | Secondary end point(s) |
Pharmacokinetic parameters for FF and VI: maximum observed
concentration at steady-state (Cmax), area under the concentration-time curve (AUC(0-t), AUC(0-4) and time of maximum observed concentration at steady state (Tmax) on Day14
• Glucose weighted mean 0–4 hr on Day 14
• Potassium weighted mean 0–4 hr on Day 14
• Serum cortisol weighted mean (0–12hr) on Day 14 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
FF and VI on Day 14
Glucose and potassium on Day 14
Serum cortisol on Day 14 |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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?
| Yes |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 6 |
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