Dymista Allergen Chamber - Onset of Action Study
Condition: Seasonal Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal
Intervention: Treatment A (Dymista): Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 3; Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 5; Treatment A (Dymista): Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 5; Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 3
Intervention description: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 3; Single dose, one spray in each nostril of Placebo nasal spray at Visit 5; Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 5; Single dose, one spray in each nostril of Placebo nasal spray, at Visit 3
Intervention MeSH terms: Fluticasone; Xhance; Azelastine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The study will be a single-center, randomized, placebo-controlled, double-blind, and two-period cross-over trial.
Masking: Double (Participant, Investigator)
Masking description: Blinding by overlabelling of Dymista and Placebo bottles.
Enrollment: 216.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      This study is to assess the onset of action of fixed drug combination of azelastine
      hydrochloride and fluticasone propionate nasal spray (Dymista) in treating the nasal symptoms
      of seasonal allergic rhinitis (SAR) induced by an allergen challenge in an Environmental
      Exposure Unit (EEU).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide written informed consent.

          2. Male or female subjects (childbearing and non-childbearing potential, non-childbearing
             potential defined as females with no menstruation for at least 1 year at screening and
             documented Follicle-Stimulating Hormone (FSH) > 35 IU/L) aged 18 to 55 years
             (inclusive) at screening.

          3. History of SAR to ragweed pollen for at least the previous 2 ragweed pollen seasons.

          4. Positive skin prick test (SPT) response to ragweed pollen (allergen induced wheal
             diameter at least 3 mm larger than the negative control). A test performed at Cliantha
             Research in the previous 12 months may be used to qualify the subject.

          5. Willingness to complete all study visits.

             To be eligible for Visit 2 EEU, a subject must additionally comply with the following
             criteria:

          6. Asymptomatic or with mild symptoms during the baseline recording of symptoms prior to
             start of the screening EEU (Visit 2):

             • Total Nasal Symptom Score (TNSS) ≤ 3/12 with the score for each symptom being less
             than 2.

             To be eligible for Visit 3, a subject must additionally comply with the following
             criteria during Visit 2 EEU:

          7. Demonstrate adequate symptomology:

             • TNSS ≥ 6/12 on at least two Electronic Patient Data Acquisition Tablet (ePDAT TM)
             time point assessments during hours 0-2 in the EEU (Visit 2), with at least one
             occurring during the last two time points. Additionally, subjects will be required to
             meet a score of at least 2/3 for runny nose at least twice during hours 0-2 in the
             EEU, with at least one occurring during the last two time points.

             To be eligible for randomization (Visit 3), a subject must additionally comply with
             the following criteria:

          8. Demonstrate adequate symptomology:

               -  TNSS ≥ 6/12 on at least two ePDATTM time point assessments during hours 0-2 in
                  the EEU (Visit 3), with at least one occurring during the last two time points.
                  Additionally, subjects will be required to meet a score of at least 2/3 for runny
                  nose at least twice during hours 0-2 in the EEU, with at least one occurring
                  during the last two time points.

               -  No evidence of complete nasal blockage on either one or both sides on anterior
                  rhinoscopy within 30 minutes prior to dosing.

        Exclusion Criteria:

        Safety concerns:

          1. History of allergic reaction to azelastine hydrochloride or fluticasone propionate or
             one of the excipients of the study treatments (e.g. benzalkonium chloride, phenylethyl
             alcohol, microcrystalline cellulose) or a component of the container.

          2. History of anaphylaxis, cardiovascular, pulmonary, hepatic, renal, gastrointestinal,
             haematological, endocrine, metabolic, psychiatric, neurological, or other disease at
             screening that may affect subject safety during the study or evaluation of the study
             endpoints at the discretion of the Investigator and/or designee.

          3. Subjects with a current diagnosis of asthma or subjects with measured Forced
             Expiratory Volume in 1 Second (FEV1) <75% of the predicted value using Global Lung
             Function Initiative set from 2012 for references.

          4. Pregnant, breast-feeding or planning a pregnancy during the study and women of
             childbearing potential not using adequate contraception. Women of childbearing
             potential not abstinent or using a highly effective method of birth control defined as
             those which result in a low failure rate (i.e. <1% per year) when used consistently
             and correctly such as implants, injectables, combined oral contraceptives, hormonal
             Intrauterine Devices (IUDs), barrier methods, or tubal ligation started at least 4
             weeks prior to screening.

             Lack of suitability for the study:

          5. Previous and concomitant treatments: use of prohibited therapies (Antihistaminic
             agents, all presentations; Theophylline, all presentations; Cromolyn sodium, all
             forms; Nedocromil sodium; Salbutamol, all presentations; Leukotriene modifiers, all
             presentations; Corticosteroids (inhaled, oral, intravenous); Topical corticosteroids
             (ocular, intranasal); Corticosteroids (intramuscular or intra-articular);
             Decongestants, all forms; Immunotherapy; Systemic antibiotics; Tricyclic
             antidepressants and Monoamine Oxidase (MAO) inhibitors; Any cytochrome P450 3A4
             inhibiting or inducing drug (e.g. ritonavir, cobicistat, ketoconazole, itraconazole,
             erythromycin, cimetidine, rifampicin, St. John's wort (Hypericum perforatum) etc.) not
             allowed within specific time frames prior to Screening and/or not allowed/allowed only
             with restrictions during the study, as specified in the study protocol; use of any
             medication considered to have an influence on the outcome of the study during the EEU
             session, at the discretion of the Investigator and/or designee.

          6. Subjects with (expected) clinically relevant symptoms at the timing of the scheduled
             EEU assessments due to concomitant allergies, i.e. history of allergic response to the
             causative allergen, at the discretion of the Investigator. Subjects with a positive
             SPT for cats and/or dogs are acceptable if the subject avoids cats and/or dogs for the
             duration of the study.

          7. Concomitant diseases: abnormalities during the screening visit (Visit 1) or Visit 2
             that might interfere with study results as determined by the Investigator and/or
             designee.

          8. Presence of a severely deviated septum, septal perforation, structural nasal defect or
             large nasal polyps causing obstruction as determined by the Investigator.

          9. Acute conditions: any acute illness within 7 days prior to the screening visit (Visit
             1) or Visit 2, including acute conjunctivitis or any other ocular infection, at the
             discretion of the Investigator and/or designee.

         10. History of increased ocular pressure, glaucoma, cataracts, and/or central serous
             chorioretinopathy (CSCR).

         11. Presence of or ongoing tuberculosis, untreated local or systemic fungal or bacterial
             infections, systemic viral or parasitic infections or ocular herpes simplex.

         12. Recent nasal ulcers, mucosal erosion, nasal surgery, or nasal trauma, that might
             interfere with study results as determined by the Investigator and/or designee.

         13. Exposure to chickenpox or measles within 4 weeks prior to the screening visit or
             during the study.

         14. Acute or chronic sinusitis or non-allergic rhinitis, at the discretion of the
             Investigator and/or designee.

         15. Exposure to another investigational product within the last 30 days prior to
             screening.

         16. History of malignancy within the past five years, except for basal cell skin
             carcinomas that have been treated with no recurrence for at least 3 months.

         17. Neurological or psychiatric disease or drug or alcohol abuse which would interfere
             with the subject's proper completion of the protocol assignment. Subjects with a
             positive urine drug screen will be excluded.

         18. Subjects undergoing surgical procedures with general anaesthesia within 90 days prior
             to screening or who plan to undergo surgery/hospitalization during the study.

             Administrative reasons:

         19. Vulnerable subjects (such as persons who are institutionalized).

         20. Positive alcohol or drug test during screening visit (Visit 1)

         21. Public health emergency (e.g. COVID-19): subjects not complying to Public health
             guidelines (e.g. self isolation etc.), at the discretion of the Investigator's and/or
             designee, or subjects with a positive COVID-test at Visit 2.