| 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 | 18.1 |
| 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 |
| The primary objective of this study is to demonstrate non-inferiority of RELVAR ELLIPTA 100/25 once-daily to SERETIDE ACCUHALER/DISKUS 250/50 twice-daily in adult and adolescent subjects 12 years of age and older with persistent bronchial asthma, adequately controlled on twice-daily ICS/LABA. |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Genetic Research
Objectives:
The objectives of the genetic research are to investigate the relationship between genetic
variants and:
- Response to medicine, including any treatment regimens under investigation in this study or any concomitant medicines;
- Asthma susceptibility, severity, and progression and related conditions |
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| E.3 | Principal inclusion criteria |
A subject will only be eligible for inclusion in this study at the screening visit (Visit 1) 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. Type of Subject: Subjects must be outpatients ≥12 years of age at Visit 1 who have had a diagnosis of sthma, as defined by the National Institutes of Health [NIH, 2007], for at least 12 weeks prior to Visit 1 (Note: Countries with local restrictions prohibiting enrolment of adolescents will enroll subjects ≥18 years of age only).
3. Gender: Subjects may be male or an eligible female.
An eligible female is defined as having non-childbearing potential or having childbearing potential and a negative urine pregnancy test at Screening and agrees to use an acceptable method of birth control consistently and correctly. The following is the GSK list of acceptable, highly effective methods for avoiding pregnancy with failure rates of less than 1% per year:
a. Abstinence from penile-vaginal intercourse, when this is the female’s preferred and usual lifestyle [Hatcher, 2007a]
b. Oral Contraceptive, either combined or progestogen alone [Hatcher, 2007a]
c. Injectable progestogen [Hatcher, 2007a]
d. Implants of etonogestrel or levonorgestrel [Hatcher, 2007a]
e. Estrogenic vaginal ring [Hatcher, 2007a]
f. Percutaneous contraceptive patches [Hatcher, 2007a]
g. Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label [Hatcher, 2007a]
h. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject [Hatcher, 2007a]. For this definition, “documented” refers to the outcome of the investigator's/designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records.
i. Male condom combined with a female diaphragm either with or without a vaginal spermicide (foam, gel, film, cream, or suppository) [Hatcher, 2007b].
Note: A urine pregnancy test will be performed at screening, randomization, at the end of treatment and at the follow up phone contact.
4. Severity of Disease: Subjects must have a FEV1 of ≥80% of the predicted normal value, as confirmed by central overread of spirometry results. Predicted values will be based upon Global Lung Function Initiative (GLI) [Quanjer, 2012] equations for spirometry reference values.
5. Asthma Therapy Prior to Visit 1: Subjects are eligible if they have received mid dose ICS plus LABA (equivalent to FP/salmeterol 250/50 twice daily or an equivalent combination via separate inhalers) for at least the 12 weeks immediately preceding Visit 1.
6. Short-Acting Beta2-Agonists (SABAs): All subjects must be able to replace their current SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use, as needed, for the duration of the study. Subjects must be able to withhold albuterol/salbutamol for at least 6 hours prior to study visits.
7. If in the opinion of the investigator the subject’s asthma is well controlled.
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|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study at the screening visit (Visit 1) if any of the following criteria apply:
1. History of Life-Threatening Asthma: Defined for this protocol as an asthma episode that required intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 5 years.
2. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is:
a) not resolved within 4 weeks of Visit 1 and led to a change in asthma management or,
b) in the opinion of the Investigator, expected to affect the subject’s asthma status or the subject’s ability to participate in the study.
3. Asthma Exacerbation: Any asthma exacerbation
(a) requiring oral corticosteroids within 12 weeks of Visit 1 or
(b) resulting in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
4. Concurrent Respiratory Disease: A subject must not have current evidence of
a. Atlectasis
b. Bronchopulmonary dysplasia
c. Chronic bronchitis
d. Chronic obstructive pulmonary disease
e. Pneumonia
f. Pneumothorax
g. Interstitial lung disease
h. Or any evidence of concurrent respiratory disease other than asthma
5. 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 as risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to the following: (Please see table in the protocol)
6. 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.
7. 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. Known or suspected sensitivity to the constituents of RELVAR ELLIPTA, SERETIDE ACCUHALER/DISKUS or FP 250 (i.e., drug, lactose or magnesium stearate).
b. Milk Protein Allergy: History of severe milk protein allergy.
8. Concomitant Medication: Administration of prescription or non-prescription medication that would significantly affect the course of asthma, or interact with study drug (Section 6.10).
9. Immunosuppressive Medications: A subject must not be using or require the use of immunosuppressive medications during the study.
10. 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, including visit schedule and completion of the daily diaries.
11. 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).
12. Affiliation with Investigator’s Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, subinvestigator, study coordinator, or employee of the participating investigator. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in clinic visit evening (PM) FEV1 (pre-bronchodilator and predose) at the end of the 24-week treatment period |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At the end of the 24-week treatment period |
|
| E.5.2 | Secondary end point(s) |
1. Change from baseline in the percentage of rescue-free 24-hour periods during the 24-week treatment period
2. Change from baseline in the percentage of symptom-free 24-hour periods during the 24-week treatment period
3. Change from baseline in morning (AM) PEF averaged over the 24-week treatment period
4. Percentage of subjects controlled defined as an Asthma Control Test (ACT) score ≥20 at the end of the 24-week treatment period
5. Change from baseline in evening (PM) PEF averaged over the 24-week treatment period |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
For secondary endpoint 1 and 2: During the 24-week treatment period
For secondary endpoint 3 and 5: Averaged over the 24-week treatment period
For secondary endpoint 4: At the end of the 24-week treatment period |
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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 | 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) | 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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 | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 70 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Chile |
| Czech Republic |
| Germany |
| Italy |
| Korea, Republic of |
| Mexico |
| Netherlands |
| Romania |
| Russian Federation |
| Spain |
| United States |
|
| 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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| The end of the study is defined as the last subject’s last contact. |
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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 | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| 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 | 0 |
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