Study Of Allergic Rhinitis In Patients Who Also Have Asthma
Condition: Asthma
MeSH terms: Rhinitis; Asthma; Rhinitis, Allergic
Intervention: fluticasone propionate/salmeterol (FSC); montelukast (MON); fluticasone propionate (FP); placebo nasal; ADVAIR DISKUS; placebo capsule; placebo DISKUS
Intervention description: fluticasone propionate/salmeterol DISKUS combination; montelukast capsule; fluticasone propionate aqueous nasal spray; vehicle placebo nasal spray; ADVAIR DISKUS; placebo capsule; placebo DISKUS
Intervention MeSH terms: Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Montelukast
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 725.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Allergic Rhinitis; Asthma

Summary:

      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.
    

Eligibility criteria:

        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             during the study will be withdrawn.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