| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Adolescent and Adult Subjects with Asthma and
Exercise-Induced Bronchoconstriction |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 20.0 |
| 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 protective effect of fluticasone furoate/vilanterol (FF/VI) 100/25 mcg once-daily compared with fluticasone propionate (FP) 250 mcg twice-daily against exercise-induced bronchoconstriction in adolescent and adult subjects aged 12 to 50 with persistent asthma |
|
| E.2.2 | Secondary objectives of the trial |
|
| 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. Informed consent: Subjects must give their signed and dated written informed consent to participate prior to commencing any study related activities.
2. Age Range: 12 to 50 years of age, inclusive, at Visit 1 (Screening).
3. Diagnosis: A diagnosis of asthma, as defined by the National Institutes of Health [NIH, 2007], for at least 12 weeks prior to Visit 1.
4. Asthma Severity: Subjects must have a pre-bronchodilator FEV1 of ≥70% of the predicted normal value. Predicted values will be based upon Global Lung Function Initiative (GLI) [Quanjer, 2012] equations for spirometry reference values.
5. Evidence of EIB: Subjects must answer “Yes” to at least 2 of the following 3 questions reflecting on the previous 12 months:
- Are you short of breath during exercise or other physical exertion?
- Do you wheeze after exercise or other physical exertion?
- Do you cough after exercise or other physical exertion?
6. Concurrent Anti-Asthma Therapy: Subjects must be taking low- to moderate dose inhaled steroids for 12 weeks prior to Visit 1 in order to participate with no change in dose for the 4 weeks prior to Visit 1. Example dosages considered appropriate for study participation are outlined in the SRM.
7. Gender: Subjects may be male or an eligible female.
A female is eligible to enter and participate in the study if she is of:
Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile).
Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, > 45 years, in the absence of hormone replacement therapy.
OR
Child bearing potential, has a negative pregnancy test at screening, and agrees to acceptable contraceptive methods approved in their local country, when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study – screening to follow-up contact). See Appendix 5.
8. Albuterol/salbutamol Use: All subjects must be able to replace their current short-acting beta2-agonist (SABA) with albuterol/salbutamol, to be used only on an as-needed basis for the duration of the study. Each subject must be judged capable of withholding albuterol/salbutamol for at least 6 hours prior to performing spirometric evaluations.
9. Physical Capacity: Each subject must be physically able to perform the exercise challenges on a treadmill when bronchodilators have been withheld. |
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria
apply:
1. Intermittent Asthma, Seasonal Asthma, or Exercise-Induced
Bronchoconstriction Only: Subjects with only intermittent or seasonal asthma or only exercise-induced asthma are excluded from participation in this study.
2. History of Life-threatening Asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 10 years.
3. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or that resulted in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
4. Symptomatic Allergic Rhinitis: Subjects with symptomatic allergic rhinitis at Visit 1 may be treated for up to four weeks with intranasal corticosteroids followed by a repeat screening visit to determine eligibility prior to entry into the study. Subjects that continue to be symptomatic after up to four weeks of treatment will be excluded.
5. 12-Lead Electrocardiogram (ECG): A subject is not eligible if he/she has an abnormal, clinically significant ECG as determined by the investigator at the Screening Visit.
6. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
7. Respiratory Infection: 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.
8. Concurrent Respiratory Disease: A subject must not have current evidence of:
a. Atelectasis
b. Bronchopulmonary dysplasia
c. Chronic bronchitis
d. Chronic obstructive pulmonary disease (current or past diagnosis including asthma/COPD overlap)
e. Pneumonia
f. Pneumothorax
g. Interstitial lung disease
h. Or any evidence of concurrent respiratory disease other than asthma
9. Other Concurrent Diseases/Abnormalities: A subject must not have any clinically significant, uncontrolled condition, or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to, the following: (Table 1 Page 33 of the protocol)
10. Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study, whichever is longer of the two periods.
11. Allergies:
a) Drug Allergy: Any adverse reaction including immediate or delayed
hypersensitivity to any beta2-agonist, sympathomimetic drug, or any
intranasal, inhaled, or systemic corticosteroid therapy, or excipients used with FF/VI 100/25 or FP 250 (i.e., drug, lactose or magnesium stearate).
b) Milk Protein Allergy: History of severe milk protein allergy.
c) Latex Allergy: History of allergy or sensitivity to latex that in the opinion of the investigator contraindicates the subject’s participation in the study.
12. Concomitant Medication: Administration of prescription or non-prescription
medication that would significantly affect the course of asthma, or interact with study drug (see Prohibited Medication Section 7.10 for a list of prohibited medications and washout times required prior to Visit 1).
13. Immunosuppressive Medications: A subject must not be using or require the use of immunosuppressive medications during the study.
14. Compliance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the investigator) to impair compliance with any aspect of this study protocol
15. Tobacco/Marijuana Use: Current tobacco smoker or has a smoking history of ≥10 pack-years (20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products or inhaled marijuana within the past 3 months (e.g., cigarettes, cigars, electronic cigarettes, or pipe tobacco).
(Please refer to the protocol for remaining Criteria's P 34) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Maximal percent decrease from pre-exercise FEV1 following exercise challenge at 12 hours post evening dose at the end of the 2-week treatment period |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Maximal percent decrease from pre-exercise FEV1 following exercise challenge at 23 hours post evening dose at the end of the 2-week treatment period
- Proportion of subjects with a 30 minute post-challenge FEV1 that was no more than 5% lower than their pre-exercise FEV1 following the exercise challenge at 12 hours
and 23 hours post evening dose at the end of the 2-week treatment period
- Weighted mean for percentage decrease from pre-exercise FEV1 following exercise challenge at 12 hours and 23 hours post evening dose (weighted mean 0-60 min) at the end of the 2-week treatment period |
|
| 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 | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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) | 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? | Yes |
| 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 years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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