| 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 | 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 |
|
| 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 that treatment with Fluticasone
Furoate/GW642444 Inhalation Powder once-daily administered in the evening
significantly decreased the risk of severe asthma exacerbations as measured by time to first severe asthma exacerbation when compared with the same dose of Fluticasone Furoate Inhalation Powder alone administered once-daily in the evening in subjects 12 years of age and older with asthma. This study will establish the safety as well as demonstrate benefit of the addition of a LABA to an ICS by utilizing an endpoint (time to first severe asthma exacerbation) that informs on both safety and efficacy. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Type of Subject: Outpatient
2. Age: 12 years of age or older at Visit 1 (or 18 years of age or older if local regulations or the regulatory status of study medication permit enrolment of adults
only).
3. Gender: Male or eligible female
To be eligible for entry into the study, males of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by
the following:
• Male partner who is sterile prior to the female subject’s entry into the study and
is the sole sexual partner for that female subject
• Implants of levonorgestrel or etonogestrel
• Injectable progestogen
• Oral contraceptive (either combined estrogen/progestin or progestin only)
• Any intrauterine device (IUD) with a documented failure rate of less than 1%
per year
• Estrogenic vaginal ring
• Double barrier method – spermacide plus a mechanical barrier (e.g., spermacide
plus a male condom or spermacide and female diaphragm)
• Percutaneous contraceptive patches
• Females of childbearing potential who are not sexually active must commit to
complete abstinence from intercourse throughout the clinical trial and for a
period after the trial to account for elimination of the drug (minimum of six
days)
• Female subjects should not be enrolled if they are pregnant, lactating or plan to
become pregnant during the time of study participation. A serum pregnancy test
is required for females of childbearing potential at the initial screening visit
(Visit 1), Visit 5, Visit 7, Visit 10 and Visit 13/Early Withdrawal. A urine
pregnancy test will be performed at Visits 2 through 4, Visits 8 through 9, Visits
11 through 12 and the follow-up contact.
4. Asthma Diagnosis: A diagnosis of asthma as defined by the National Institutes of Health at least 1 year prior to Visit 1.
5. Severity of Disease: A best FEV1 of 50% to 90% of the predicted normal value at
Visit 1. NHANES III predicted values will be used for subjects ≥12 years of age. If a subject is recorded as having Hispanic or Latino ethnicity, then the Mexican-American equations will be used (irrespective of race). If a subject is recorded as being of African American/African Heritage race, then the African American equations will be used. If a subject is recorded as being of Asian race, then the Asian equations will be used. Otherwise, the Caucasian equations will be used.
6. Reversibility of Disease: Demonstrated a ≥12% and ≥200mL reversibility of FEV1
within 10 to 40 minutes following 2 to 4 inhalations of albuterol/salbutamol
inhalation aerosol (if required, spacers are permitted for reversibility testing only) or
equivalent nebulized treatment with albuterol/salbutamol solution at screening.
7. Current Anti-Asthma Therapy: Subjects must be using an approved dose of an
ICS (as per specific prescribing information) for at least 12 weeks preceding Visit 1
and at a stable dose for at least 4 weeks preceding Visit 1 for further information See protocol page 19.
8. Asthma Exacerbation History: All subjects must have a history of one or more
asthma exacerbations requiring treatment with oral/systemic corticosteroids or
emergency department visit or in-patient hospitalization for the treatment of asthma
within the previous 12 months.
Note: Subjects who have experienced an asthma exacerbation requiring
oral/systemic oral corticosteroids in the 4 weeks prior to Visit 1 can not be enrolled
in the study due to the 4 week washout of the oral/systemic corticosteroids, but can
enter Visit 1 once the washout period has been met.
9. Short-Acting Beta2-Agonists: All subjects must be able to replace short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as needed for the duration of the study. Subjects must be able to withhold all inhaled short-acting beta-sympathomimetic bronchodilators for at least 6 hours prior to study visits.
10. Informed Consent: All subjects must be able and willing to give written informed
consent to take part in the study.
|
|
| E.4 | Principal exclusion criteria |
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. Concurrent Respiratory Disease: A subject must not have current evidence of
pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease,
bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive
pulmonary disease, or respiratory abnormalities other than asthma.
3. 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 results if the condition/disease exacerbated during the study.
4. Oral Candidiasis: A subject will not be eligible for the run-in if he/she has clinical
visual evidence of oral candidiasis at Visit 1.
5. Investigational Medications: A subject must not have participated in a study
(including a non-interventional study) or used any investigational drug (including
devices) within 30 days prior to Visit 1 or within ten half-lives (t1/2) of the prior
investigational study (whichever is longer of the two).
6. Previous Participation: A subject may not have previously been randomized to
treatment in a Phase III Fluticasone Furoate/GW642444 Inhalation Powder study
(i.e., HZA106825, HZA106827, HZA106829, HZA106839, HZA106851).
7. 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 the Novel Dry Powder Inhaler (i.e., lactose or magnesium stearate).
8. Milk Protein Allergy: History of severe milk protein allergy.
9. Immunospressive medications: A subject must not be using or require use of
immunosuppressive medications during the study.
Note: Immunotherapy for the treatment of allergies is allowed during the study
provided it was initiated 4 weeks prior to Visit 1 and subjects remain in the
maintenance phase for the duration of the study.
10. Attendance: A subject will not be eligible if he/she or his/her parent or legal
guardian has any infirmity, disability or geographical location which seems likely (in
the opinion of the investigator) to impair compliance with any aspect of this study
protocol or scheduled visits to the study center and non-compliance with study
medication or procedures (i.e., completion of diary card).
11. Neurological or psychiatric disease or history of drug or alcohol use which would
interfere with the subjects’ proper completion of the protocol requirements.
12. Concomitant Medications: Administration of any other prescription or over the counter medication which would significantly affect the course of asthma, or interact with sympathomimetic amines, such as: anticonvulsants (barbiturates, hydantoins, carbamazepine), polycyclic antidepressants, beta-adrenergic blocking agents (both cardio-selective and non-selective), phenothiazines, monoamine oxidase (MOA) inhibitors. Please refer to the SPM for further details.
13. Tobacco Use: A subject may not have used inhaled tobacco products within the past three months (i.e., cigarettes, cigars or pipe tobacco) or have historical use of 10 pack years or more (e.g., 20 cigarettes/day for 10 years).
14. 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.
15. Cytochrome P450 3A4 (CYP 3A4) Inhibitors: A subject is not eligible if he/she is receiving a strong CYP 3A4 inhibitor within 4 weeks of Visit 1 (e.g., ritonavir,
ketoconazole, itraconazole).
For further information re: Exclusion criteria for randomization to treatment please view page 22 of the protocol.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this study is the time to first severe asthma
exacerbation. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Rate of severe asthma exacerbation per subject per year
• Change from baseline at Week 36 in evening pre-dose trough FEV1 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Rate of Severe asthma exacerbation at 52 Weeks
• FEV1 at Week 36 |
|
| 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 | 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?
| 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 | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
| Argentina |
| Australia |
| Japan |
| Mexico |
| Philippines |
| Russian Federation |
| Ukraine |
| United States |
|
| 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
|
| End of trial is last subject last visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 22 |
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