Official Title: “A Multicenter, Randomized, Double-Blind, Triple-Dummy, Placebo-Controlled, Parallel Group, Four-Week Study Assessing the Efficacy of Fluticasone Propionate Aqueous Nasal Spray 200mcg QD Versus Montelukast 10mg QD in Adolescent and Adult Subjects With Asthma and Seasonal Allergic Rhinitis Who Are Receiving ADVAIR DISKUS® 100/50mcg BID or Placebo BID”

This study will last up to 6 weeks. Subjects will visit the clinic up to 5 times. Certain clinic visits will include a physical examination, medical history review, and lung function tests. All study related medications and medical examinations will be provided at no cost to the subject. The drugs used in this study are approved for the age group under study.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2007

Intervention(s) in this Clinical Trial

• Drug: fluticasone propionate/salmeterol
• Drug: montelukast
• Drug: fluticasone propionate

Primary Measures

• Morning Peak Expiratory Flow
• Mean change from baseline at endpoint in percentage of asthma symptom-free days

Secondary Measures

• Total Nasal Symptom Scores Morning Forced Expiratory Volume in 1 Second Asthma Symptom-Free Days Asthma Rescue-Free Days
• The secondary efficacy measures are: Rhinitis: For treatment comparisons between FSC+FPANS and FSC+MON to assess superiority:
• Mean change from baseline in subject-rated daily, total nasal symptom scores (D-TNSSW1-2 : equal to the sum of symptom scores assessing rhinorrhea, nasal congestion, nasal itching, and sneezing) averaged over Weeks 1-2
• Mean change from baseline in subject-rated nighttime total nasal symptom scores (N-TNSSW1-2: the sum of symptom scores assessing AM nasal congestion upon wakening,
• difficulty in going to sleep due to nasal symptoms, and nighttime awakenings due to nasal symptoms) averaged over Weeks 1 - 2
• Asthma: For treatment comparisons FSC vs MON to assess superiority and between FSC vs FSC+MON to assess equivalence:
• Mean change from baseline at endpoint in predose AM FEV1
• Mean change from baseline at endpoint in percentage of asthma rescue-free days Endpoint is defined as the average of the last week's worth of data.
• Related efficacy measures will include subject-rated overall satisfaction with treatment (related to percentage of asthma symptom-free days), evening PEF (related to pre-dose AM FEV1), asthma symptom scores (related to percentage of asthma symptom-free
• days), albuterol/salbutamol use (related to percentage of asthma rescue-free days), and subject-rated daytime and nighttime individual nasal symptom scores averaged over weeks 1-2
• (D-INSSW1-2, N-INSSW1-2) (related to D-TNSSW1-2 and N-TNSSW1-2, respectively). In addition, all total and individual nasal symptom scores will be summarized over weeks 1-4 for descriptive purposes.

INCLUSION CRITERIA:

• A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:
• 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.
• 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.
• Age: 15 years and older.
• 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.
• 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).
• One of the following inhaled corticosteroids taken at the corresponding daily dose:
• criteria.
• Inhaled Corticosteroid (Total Daily Dose) Beclomethasone dipropionate (≤420mcg)
• Beclomethasone dipropionate HFA (≤240mcg) Budesonide (≤400mcg) Flunisolide (≤1000mcg)
• Fluticasone propionate inhalation aerosol (≤220mcg) Fluticasone propionate inhalation powder (≤250mcg) Mometasone furoate (≤220mcg) Triamcinolone acetonide (≤1000mcg) Subjects taking ADVAIR 100/50mcg BID are eligible to replace ADVAIR with FLOVENT HFA 110mcg BID for 14 days prior to Visit 1. This change will be at the Investigator's clinical discretion, taking each individual's current and past asthma stability into account. The subject must be aware of the risks and benefits of switching their medication and acknowledge this by signing an informed consent prior to any change in the subject's medication regimen.
• 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].
• 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).
• AND •A positive skin test reaction to a geographically relevant seasonal allergen, as determined by the skin prick method, within 24 months prior to or at Visit 1.
• For the purposes of this study, a positive skin test reaction is defined as a wheal diameter that is at least 3mm greater than diluent control using 1:20 W:V glycerinated solution.
• •At Visit 2, subjects must also be experiencing minimum rhinitis symptoms as defined in Section 5.2.3, "Randomization Criteria", and in Section 6.2 of the protocol.
• Geographical Location: Active residence within a geographical region where exposure to a relevant seasonal allergen is expected to be significant during the entire study period.
• Note: The principal investigator is responsible for tracking and recording pollen counts for geographically relevant seasonal allergens throughout the entire study. Alternatively, this information may be obtained from a reputable source from within the same geographical area.

EXCLUSION CRITERIA:

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:
• Currently Diagnosed with Life-Threatening Asthma: An episode or episodes of asthma requiring intubation associated with hypercapnia, respiratory arrest, or hypoxic seizures.
• Asthma Instability: Hospitalization for asthma within 6 months of Visit 1.
• Concurrent Respiratory Disease: Current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, chronic bronchitis, emphysema, or any other respiratory abnormalities other than asthma.
• Nasal Obstruction: Severe physical obstruction of the nose (e.g., deviated septum) that could affect the deposition of double-blind intranasal study drug.
• Nasal History: History of nasal septal perforation or recent nasal septal surgery.
• Other Concurrent Conditions/Diseases: Any evidence of rhinitis medicamentosa, history of glaucoma and/or cataracts or ocular herpes simplex, or 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.

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.
• Drug Allergy: Any immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, leukotriene modifier, or any intranasal, inhaled, or systemic corticosteroid therapy, or sensitivity to aspirin or other NSAIDS. Subjects with severe milk protein allergies are also excluded from participation.
• 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.
• 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
• 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.
• Excluded Rhinitis Medications: The following rhinitis medications 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:
• Medication (Exclusion Period Prior to Visit 1) Intranasal and ocular corticosteroids (28 days) Leukotriene modifiers (e.g., Singulair, Accolate, Zyflo) (28 days) Intranasal and ocular cromolyn (14 days) Long-acting antihistamines (e.g., loratadine, cetirizine) (10 days) Short-acting antihistamines (includes prescription and OTC) (72 hours) Oral and intranasal decongestants (72 hours) Intranasal anticholinergics (e.g., Atrovent) (24 hours)
• Excluded Asthma Medications: The following asthma medications must be withheld during the corresponding "exclusion period" prior to Visit 1.
• 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" as shown below.
• 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:
• Medicationª (Exclusion Period Prior to Visit 1 and/or Visit 2) Inhaled corticosteroid/long-acting beta2-agonist combination product (e.g., ADVAIR) (14 days)
• Inhaled anticholinergics (e.g., Atrovent, Combivent, Spiriva) (24 hours) Theophylline products (48 hours) Inhaled cromolyn or nedocromil (24 hours) Inhaled corticosteroids (12 hours) Long-acting beta2-agonists (e.g., Foradil, SEREVENT™) (14 days) Oral beta2-agonists (12 hours) Inhaled short-acting beta2-agonists^b (e.g., Proventil) (6 hours) Xolair (12 months)
• 1. For the leukotriene modifier "exclusion period" prior to Visit 1, refer to Exclusion
• Criterion 11.
• 2. Replaced at Visit 1 with albuterol/salbutamol.
• 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.
• 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.
• Positive Pregnancy Test: A positive pregnancy test at Visit 1.
• Tobacco Use: Greater than a 10 pack-year history of cigarette smoking or use of any tobacco products within 1 year of Visit 1. This includes cigarettes, cigars, pipe, chewing tobacco, and snuff.
• Note: Pack years = number of cigarettes smoked per day divided by 20, multiplied by the number of years of smoking.
• Questionable Validity of Consent: Any infirmity or disability that would limit the subject's consent or geographic location that would limit the compliance for scheduled visits.
• Investigational Medications: Use of any investigational drug within 30 days of Visit 1.
• 3rd shift/Nighttime employment: Any employment during the nighttime hours (10 p.m. - 6 a.m.) or 3rd shift.
• Site affiliation: Participation of anyone associated with the administration of the study or their immediate family members

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: GlaxoSmithKline

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials, MD Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00296491

Study ID Number: ADA103575

ClinicalTrials.gov Identifier: NCT00296491

Health Authority: United States: Food and Drug Administration