| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Persistent asthma and seasonal allergic rhinitis. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039776 |
| E.1.2 | Term | Seasonal allergic rhinitis |
|
| 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 main objective of this study are to show that fluticasone propionate/salmeterol combination product 100/50mcg (FSC) BID (available as Seretide DISKUS) is superior to montelukast 10mg OD (available as Singulair) as monotherapy for asthma, and that Montelukast administered concurrently with FSC adds no additional benefit to FSC alone in improving asthma control in a population of subjects with allergic asthma. |
|
| E.2.2 | Secondary objectives of the trial |
| To show that in the presence of FSC, fluticasone propionate aqueous nasal spray 200mcg (FPANS) OD (available as FLIXONASE) is superior to Montelukast for control of rhinitis symptoms in this population. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:
1. Consent: A signed and dated written informed consent must be obtained from the subject or subject’s legally acceptable representative prior to study participation. An informed consent must be signed prior to any change in the subject’s medication regimen, including withholding medications prior to Visit 1.
2. Gender: Male or female.
Females are eligible to participate only if they are currently not pregnant and not lactating. Females of child-bearing potential will be required to use a highly effective method for avoiding pregnancy (i.e., contraception with a failure rate of <1% per year). Female subjects of child-bearing potential will undergo a urine pregnancy test at Visits 1, 2, 3, and 4. Any female who becomes pregnant during the study will be withdrawn. Female subjects should not be enrolled if they plan to become pregnant during the time of study participation.
3. Age: 15 years and older.
4. Asthma Diagnosis: A diagnosis of persistent asthma, for at least three months, as defined by the following American Thoracic Society definition:
Asthma is a clinical syndrome characterized by increased responsiveness of the tracheobronchial tree to a variety of stimuli. The major symptoms of asthma are paroxysms of dyspnea, wheezing, and cough, which may vary from mild and almost undetectable to severe and unremitting (status asthmaticus). The primary physiological manifestation of this hyperresponsiveness is variable airway obstruction. This can take the form of spontaneous fluctuations in the severity of obstruction, substantial improvements in the severity of obstruction following bronchodilators or corticosteroids, or increased obstruction caused by drugs or other stimuli [American Thoracic Society, 1987a].
NOTE: Intermittent and seasonal asthma, as well as exercise-induced bronchospasm alone, are excluded.
5. Asthma Therapy: 3 months’ prior and current use of one of the following asthma therapies, with no change in regimen during the month prior to Visit 1:
• Scheduled or as-needed inhaled or oral short-acting beta2-agonist (SABA). Subjects must be able to replace their current short-acting beta2-agonist with albuterol/salbutamol, to be used only on an as-needed basis for the duration of the study.
• Allowed non-corticosteroid controller therapy (e.g., anticholinergics and cromolyn).
• inhaled corticosteroids taken at the corresponding daily dose ( See protocol for specific details)
6. Asthma Severity: An FEV1 between 65% - 95% of predicted value at Visit 1 after withholding asthma medications as detailed in the protocol.
At Visit 2, subjects must also be experiencing minimum asthma symptoms as defined in Section 5.2.3, “Randomization Criteria”, and in Section 6.2 of the protocol.
Predicted FEV1 will be based on the National Health and Nutrition Examination Survey (NHANES III) predicted normal values [Hankinson, 1999].
7. Rhinitis Diagnosis: A diagnosis of seasonal allergic rhinitis defined as follows:
• A clinical history (written or verbal confirmation) of allergic rhinitis with the seasonal onset and offset of nasal allergy symptoms during each of the previous 2 relevant allergy seasons (captured in source documents only).
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|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Currently Diagnosed with Life-Threatening Asthma: An episode or episodes of asthma requiring intubation associated with hypercapnia, respiratory arrest, or hypoxic seizures.
2. Asthma Instability: Hospitalization for asthma within 6 months of Visit 1.
3. Concurrent Respiratory Disease: Current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, chronic bronchitis, emphysema, or any other respiratory abnormalities other than asthma.
4. Nasal Obstruction: Severe physical obstruction of the nose (e.g., deviated septum) that could affect the deposition of double-blind intranasal study drug.
5. The list of additional excluded conditions/diseases includes, but is not limited to: cardiac arrhythmias; congestive heart failure; coronary artery disease; poorly controlled diabetes, poorly controlled hypertension, poorly controlled peptic ulcer, hematologic, hepatic, or renal disease; immunologic compromise; current malignancy; current or quiescent tuberculosis, and Cushing’s or Addison’s disease.
6. Respiratory Tract Infections: Any sinus, middle ear, oropharyngeal, upper or lower respiratory tract infection that has not resolved at least 14 days immediately preceding Visit 1, or for which antibiotic therapy has not been completed at least 14 days prior to Visit 1.
7. Concurrent Medications: Concurrent use of any of the following medications that may affect the course of asthma, rhinitis, or interact with sympathomimetic amines or montelukast.
• Beta-blockers
• tricyclic antidepressants
• monoamine oxidase inhibitors
• phenobarbital
• rifampin
• ritonavir
• ketoconazole
8. Systemic Corticosteroids: Use of oral or parenteral systemic corticosteroids within 28 days of Visit 1, or requirement for more than two courses of parenteral systemic corticosteroids for asthma within 6 months of Visit 1.
NOTE: Topical hydrocortisone cream or ointment (1% or less) is permitted during the study.
9. Excluded Rhinitis Medications: rhinitis medications ( as excluded in the protocol) must be withheld during the corresponding “exclusion period” prior to Visit 1 and are not allowed any time during the study, unless dispensed as double-blind study drug.
10. Excluded Asthma Medications: asthma medications must be withheld during the corresponding “exclusion period” prior to Visit 1 ( as specified in the protocol).
These asthma medications, with the exception of an inhaled corticosteroid/long-acting beta2-agonist combination product and Xolair, may be continued during the run-in period of the study (between Visits 1 and 2), but must be withheld prior to Visit 2 for the appropriate “exclusion period”.
These asthma medications are not allowed any time after randomization at Visit 2 (with the exception of as as-needed rescue albuterol/salbutamol), unless dispensed as double-blind study drug ( see specifics in Protocol):
Inhaled corticosteroid/long-acting beta2-agonist combination product (e.g., ADVAIR)
Inhaled anticholinergics (e.g., Atrovent, Combivent, Spiriva)
Theophylline products
Inhaled cromolyn or nedocromil
Inhaled corticosteroids
Long-acting beta2-agonists (e.g., Foradil, SEREVENT™)
Oral beta2-agonists
Inhaled short-acting beta2-agonistsb (e.g., Proventil)
Xolair
a. For the leukotriene modifier “exclusion period” prior to Visit 1, refer to Exclusion Criterion 11.
b. Replaced at Visit 1 with albuterol/salbutamol.
11. Ophthalmic preparations: Use of artificial tears, eyewashes, homeopathic preparations, irrigation solutions, lubricants, sympathomimetic preparations, vasoconstrictors, or combinations of any of the aforementioned products during the study.
11. Immunosuppressive Medications: Use of immunosuppressive medications during the study.
NOTE: Immunotherapy for the treatment of allergies is allowed during the study, provided that it was not initiated within 30 days of Visit 1, the dose has remained fixed over the 30 days prior to Visit 1, and the dose will remain fixed for the duration of the study.
13. Positive Pregnancy Test: A positive pregnancy test at Visit 1.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy measures are the mean change from baseline at endpoint in morning Peak Expiratory Flow (PEF) compared between the fluticasone propionate/salmeterol combination product 100/50mcg BID (FSC) and montelukast 10mg OD (MON) treatment groups to assess superiority and compared between the FSC and FSC+Montelukast treatment groups to assess equivalence. |
|
| 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 | Yes |
| 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) | 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 | 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 | Yes |
| E.8.2.3 | Other | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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