A Comparator Study of Fluticasone Propionate Nasal Spray Verses (vs) Cetirizine in the Treatment of Seasonal Allergic Rhinitis
Condition: Rhinitis, Allergic, Perennial and Seasonal
MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Rhinitis, Allergic, Perennial
Intervention: FPNS; FPNS Placebo; Cetirizine; Cetirizine Placebo
Intervention description: Bottled, 16 gm net fill weight for 120 metered sprays with unit dose strength of 50 mcg per spray.; Bottled placebo nasal spray (vehicle for Fluticasone propionate aqueous nasal spray), 16 gm net fill weight for 120 metered sprays.; Over-encapsulated Cetirizine tablet with unit dose strength of 10 mg in High Density Poly Ethylene Bottles (20 count per bottle).; Over-encapsulated Cetirizine matching tablet High Density Poly Ethylene Bottles (20 count per bottle).
Intervention MeSH terms: Cetirizine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 682.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cetirizine; seasonal allergic rhinitis; Quality of Life; fluticasone propionate nasal spray

Summary:

      This phase IV investigational trial is being conducted to evaluate the efficacy of a 2-week
      treatment of fluticasone propionate nasal spray (FPNS) vs. cetirizine on allergic nasal and
      ocular symptoms and quality of life in adult subjects with SAR. It is hypothesized that FPNS
      provides greater nasal symptom relief than cetirizine. The primary measure used to test this
      hypothesis is the change from baseline over two weeks in reflective total nasal symptom score
      (rTNSS) compared between FPNS and cetirizine. Approximately 648 subjects will be randomized
      into a 1:1:1:1 ratio of treatment allocation across approximately twenty-five to thirty-five
      sites in the US during the 2013 fall allergy season. All subjects will be outpatients. The
      total duration of study will be approximately 21 days including 7 days of screening period,
      and 14 days of treatment period.
    

Eligibility criteria:

        Inclusion Criteria

          -  Informed consent: Subject must give their signed and dated written informed consent to
             participate. Subject must understand and be willing, able, and likely to comply with
             study procedures and restrictions. Subject must be able to read, comprehend, and
             record information in English.

          -  Subject is treatable on an outpatient basis.

          -  Age: >=18 years of age at Visit 1.

          -  Gender: Male or eligible female subjects. A female subject is eligible to participate
             if she is of non-childbearing potential (i.e., physiologically incapable of becoming
             pregnant, including any female who is post-menopausal or surgically sterile).
             Surgically sterile females are defined as those with a documented hysterectomy and/or
             bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being
             amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age
             appropriate, history of vasomotor symptoms. OR Childbearing potential with a negative
             pregnancy test at screening and agreeable to using one of the acceptable contraceptive
             methods consistently and correctly (i.e., in accordance with the approved product
             label and the instructions of the physician for the duration of the study). An
             eligible female is also not lactating nor planning on becoming pregnant during the
             study.

          -  Diagnosis of SAR, defined as documented clinical history or physician verification of
             subject reported historical SAR during each of the last two fall allergy seasons and a
             positive skin prick test (wheal >=3 millimeter [mm] larger than the negative control)
             to a prevalent local fall allergen within 12 months prior to Visit 1 or at Visit 1.

          -  Adequate exposure to local fall pollen: Subject resides within a geographical region
             where exposure to the local fall pollen to which they are sensitized is expected to be
             moderate or greater during the study period. Subject does not plan to travel outside
             the geographical region where exposure to local fall pollen to which they are
             sensitized is expected to be moderate or greater for more than 48 hours during the
             study period.

        At Visit 2, the subject must meet the following criteria

          -  Eligible subjects will need to have moderate to severe SAR symptoms, defined as a
             morning rTNSS of >=7 on at least four of the last seven days leading up to
             randomization. This includes the AM assessment on the morning of the randomization
             visit at Visit 2.

          -  Subjects should demonstrate at least a 70% compliance rate with both their placebo
             run-in study medications and their e-diary completion prior to randomization. This
             period includes the day of Visit 1 until the day before randomization at Visit 2.

          -  Subjects should have no significant change in medical condition(s) that would have
             been exclusionary at Visit 1.

          -  Subjects should not have used any prohibited medications that are detailed in the
             inclusion/exclusion criteria (including prohibited allergy medications).

          -  Subjects should not have travelled outside the local pollen region for more than 48
             hours during the run-in period.

        Exclusion Criteria

          -  Significant concomitant medical conditions, defined as but not limited to:

        Historical or current evidence of a clinically significant uncontrolled disease of any body
        system (e.g., tuberculosis, psychological disorders, eczema, uncontrolled asthma).
        Significant is defined as any disease that, in the opinion of the investigator, would put
        the safety of the subject at risk through study participation or which would confound the
        interpretation of the study results if the disease/condition exacerbated during the study.

        A severe physical obstruction of the nose (e.g., deviated septum or nasal polyp) or nasal
        septal perforation that could affect the deposition of intranasal study drug.

        Nasal (e.g., nasal septum), ocular, or throat injury, or surgery to these areas in the last
        3 months.

        Rhinitis medicamentosa. Bacterial or viral infection (e.g., common cold) of the eyes or
        upper respiratory tract within two weeks of Visit 1 or during the screening period.

        Documented evidence of acute or significant chronic sinusitis, as determined by the
        individual investigator.

        Current or history of glaucoma and/or cataracts or ocular herpes simplex. Physical
        impairment that would affect subject's ability to safely and fully participate in the
        study.

        Clinical evidence of a Candida infection of the nose. History of psychiatric disease,
        intellectual deficiency, poor motivation, substance abuse (including drug and alcohol) or
        other conditions that will limit the validity of informed consent or that would confound
        the interpretation of the study results.

        History of adrenal insufficiency.

          -  Use of corticosteroids, defined as: Intranasal corticosteroid within four weeks prior
             to Visit 1 and during the treatment period. Inhaled, oral, intramuscular, intravenous,
             ocular, and/or dermatological corticosteroid (with the exception of hydrocortisone
             cream/ointment, 1% or less) within eight weeks prior to Visit 1 and during the
             treatment period.

          -  Use of allergy medications, within a timeframe relative to Visit 1, that would prevent
             the medication from being eliminated and/or have an effect. Exclusionary timeframes
             relative to Visit 1 for five common allergy treatments are noted below Intranasal
             cromolyn (<=2 weeks from Visit 1). Intranasal or systemic decongestants (<=3 days from
             Visit 1). Intranasal or systemic (other than oral) antihistamines (<=3 days from Visit
             1).

        Leukotriene modifiers (<=3 days from Visit 1). Oral antihistamines (<=2 days from Visit 1).
        Allergy medications, other than study supplied medications, are not allowed during the
        study.

          -  Use of other medications that may affect allergic rhinitis or its symptoms, e.g., use
             of any ocular antihistamines, artificial tears, eyewashes/nasal irrigation solutions,
             homeopathic preparations, lubricants, sympathomimetic or vasoconstrictor preparations
             during the screening and treatment periods

          -  Use of any medications (prescription or non-prescription) or alcohol to induce sleep
             48-hours prior to Visit 1 and during the treatment period.

          -  Use of other intranasally administered medications (e.g., calcitonin), including
             herbals and homeopathics during the run-in (Visit 1 - Visit 2) and treatment period.

          -  Use of immunosuppressive medications within 8 weeks prior to screening and during the
             treatment period.

          -  Use of any medications that significantly inhibit the cytochrome P450 subfamily enzyme
             CYP3A4 (e.g., ritonavir, ketoconazole) during the run-in (Visit 1 - Visit 2) and
             treatment period.

          -  Known hypersensitivity to corticosteroids or any excipients present in the nasal
             spray.

          -  Known hypersensitivity to cetirizine or any excipients in the tablet.

          -  Recent exposure to an investigational study drug or device within 30 days of Visit 1.

          -  Affiliation with investigator site: Study investigators, sub-investigators, study
             coordinators, employees of a participating investigator or immediate family members of
             the aforementioned are excluded from participating in this study.

          -  Chickenpox or measles during the last 3 weeks prior to screening and is non-immune.

          -  Immunotherapy is exclusionary unless the immunotherapy was initiated >=30 days from
             Visit 1 and if 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.

          -  Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
             abuse within the last 2 years which in the opinion of the investigator could interfere
             with the subject's proper completion of the protocol requirement.