| 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 |
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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 |
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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 |
The objective of the study is to compare the effectiveness of fluticasone furoate(FF)/vilanterol (VI) Inhalation Powder (FF 100mcg/VI 25mcg or FF 200mcg/VI 25mcg) with usual asthma maintenance therapy over twelve months in a large UK primary care population of subjects with Asthma. FF/VI will be administered once-daily (QD) via the Novel Dry Powder Inhaler (NDPI).
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| E.2.2 | Secondary objectives of the trial |
The secondary objective is to compare the incidence of serious adverse events of
pneumonia during the study of fluticasone furoate (FF)/vilanterol (VI) Inhalation Powder (FF 100mcg/VI 25mcg or FF 200mcg/VI 25mcg) with usual asthma maintenance therapy over twelve months.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Informed consent: Subjects must be able to provide informed consent, have their consent signed and dated. Subjects must be able to complete the electronic subject questionnaires or allow a proxy to do so on their behalf.
2. Type of subject: Subjects with documented GP diagnosis of asthma as their primary respiratory disease.
3. Current Anti-Asthma Therapy: All subjects must be prescribed maintenance therapy and receiving ICS with or without LABA (either a fixed combination or via separate inhalers), and for at least 4 weeks prior to Visit 2.
• Other background asthma medication such as anti-leukotrienes are permitted
4. All subjects on ICS monotherapy or ICS/LABA combination (this can be a fixed dose combination or an ICS alone or LABA alone in separate inhalers) must have had symptoms in the past week prior to Visit 2. Symptoms are defined by daytime symptoms more than twice per week, use of short-acting beta2-agonist bronchodilator more than twice per week, any limitation of activities, or any nocturnal symptoms/awakening. (The symptoms are based on subject’s recall and are consistent with the GINA and in principal with the BTS/SIGN guidelines).
5. Subject questionnaires: Subjects must be able to complete the electronic subject questionnaires as well as those questionnaires that are completed by phone or provide a proxy e.g. a partner/relative/a friend who can do so on their behalf
6. Gender and Age: Male or female subjects aged 18 years of age at Visit 1
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, history of vasomotor symptoms. However in questionable cases, a blood sample with FSH > 40MIU/ml and estradiol <40pg/ml (<147 pmol/L) is confirmatory. OR
Child bearing potential has a negative urine pregnancy test at Visit 2, and agrees to one of the highly effective and acceptable contraceptive methods 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 – Visit 2 to the end of the study). The list of contraceptive methods is available in Appendix 2. |
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| E.4 | Principal exclusion criteria |
1. Recent history of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 6 months.
2. COPD Respiratory Disease: A subject must not have current evidence or GP diagnosis of chronic obstructive pulmonary disease.
3. Other diseases/abnormalities: Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the GP/ Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
4. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g., beta2-agonists, corticosteroid) or components of the inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the GP/ Investigator, contraindicates the subject’s participation will also be excluded.
5. Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 2 or within five half-lives (t½) of the prior investigational study (whichever is longer of the two), (if unsure discuss with the medical monitor prior to screening)
6. Chronic user of systemic corticosteroids: A subject who, in the opinion of the GP/Investigator, is considered to be a chronic user of systemic corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening)
7. Subjects who are using LABA without an ICS as asthma maintenance therapy.
8. Subjects who plan to move away from the geographical area where the study is being conducted during the study period and/or if subjects have not consented to their medical records being part of the electronic medical records database that is operational in the Salford area.
9. Subjects whose current medications include RELVAR are not eligible to enter the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is defined as the percentage of subjects who have either an ACT total score of ≥ 20 or an increase from baseline of ≥ 3 in ACT total score at Week 24 (6th month) assessment.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Week 24 (Visit 4, Month 6) of the study |
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| E.5.2 | Secondary end point(s) |
Secondary endpoints will include;
• Percentage of subjects with asthma control (ACT total score ≥ 20) at Weeks 12, 24, 40 and 52.
• Mean change from baseline in ACT total score at Weeks 12, 24, 40 and 52.
• Asthma-related secondary care contacts 1,2,5,6
• Asthma-related primary care contacts 1,2,3,4
• All secondary care contacts1
• All primary care contacts1, 3
• Mean annual rate of severe asthma exacerbations. A severe asthma exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids 4 (tablets, suspension, or injection) or antibiotics, an inpatient hospitalisation, or emergency department visit due to asthma that required systemic corticosteroids or antibiotics2, 4, 6.
•Number of salbutamol inhalers (adjusted to equivalence of 200 actuations) collected by the subjects from study-enrolled community pharmacies over the entire treatment period.
•Time to discontinuation or modification of initial therapy (i.e. therapy the subject is randomised to at Visit 2).
•Percentage of subjects who have an increase from baseline of ≥ 0.5 in AQLQ(s) total score at Week 52.
•Percentage of subjects who have an increase from baseline of ≥ 0.5 in AQLQ(s) environmental stimuli domain score at Week 52.
Notes defining secondary endpoints:
1. All contacts are defined as any encounter the subject may have with a doctor or nurse or other healthcare professionals working as part of the NHS (including telephone calls).
2. Contacts with the NHS or hospitalisation are defined as exacerbation-related contacts if these contacts were a direct result of an acute worsening of asthma symptoms.
3. These contacts do not include protocol-defined study-related visits/contacts defined as per the Time and Events Table (Table 4).
4. A prescription of systemic corticosteroid or antibiotics is defined as exacerbation-related if the reason the drug was given, in whole or in part, was to treat an acute worsening of asthma symptoms.
5. Contacts are defined to be asthma-related as per GP/Investigator defined normal clinical practice
6. Exacerbation-related hospitalisation includes hospitalisation that is prolonged as a result of an asthma exacerbation.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Different parts of the secondary endpoints are evaluated at different time points:
a) Weeks 12, 40 and 52
b) Baseline compared to Weeks 12, 24, 40, and 52
c) Baseline compared to Weeks 12, 24, 40, and 52
d) Captured across entire study
e) Captured across entire study
f) Captured across entire study
g) Captured across entire study
h) Captured across entire study
i) Captured across entire study
j) Captured across entire study
k) Baseline compared to Week 52
l) Baseline compared to Week 52
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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 | Yes |
| 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 | No |
| 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 | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| 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
| 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 | 67 |
| 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 | Yes |
| 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.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 12 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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