Efficacy of Co-administration of Bilastine and Montelukast in Patients With SARC and Asthma
Condition: Seasonal Allergic Rhinoconjunctivitis; Asthma
MeSH terms: Asthma; Conjunctivitis, Allergic
Intervention: Bilastine 20mg; Montelukast 10mg; Placebo Bilastine 20mg; Placebo Montelukast 10mg
Intervention MeSH terms: Montelukast
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study was a randomised (1:1:1), double-blind, double-dummy, interventional, active-controlled, parallel groups (three groups), multi-centre, multi-national, superiority clinical trial. The study plan included a 7-day (± 4) run-in period to ensure wash-out from previous forbidden treatments and to perform the tests required to ensure appropriate patient enrolment into the study. The active treatment period was 12 weeks (85 days) with a follow-up visit (phone call) at 28 days (± 4) after the End of Treatment.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: The principal investigator and study staff, subjects and monitors remained blinded to the treatment until study closure in this double-blind, double-dummy study. The identity of the study drug was revealed only if the subject experienced a medical emergency the management of which would be improved by the knowledge of the blinded treatment assignment.
As the combination therapy of Bilastine + Montelukast consisted of two tablets in contrast to monotherapy with either Bilastine or Montelukast, the double-dummy technique was applied with matching placebo for each Investigation Medicinal Product (IMP) (monotherapy with Bilastine or Montelukast) to ensure the maintenance of double-blind conditions. Therefore, each patient took 2 tablets with each dose administered.
As by randomisation list, each Patient Kit consisted of two IMP treatments (either active + placebo or active + active) in separate blisters packed in two different boxes.
Enrollment: 454.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bilastine; Montelukast; total symptom score; AQLQ

Summary:

      The purpose of this study is to compare concomitant administration of Montelukast and
      Bilastine to Montelukast and Bilastine monotherapies in patients with SARC and asthma
    

Eligibility criteria:

        INCLUSION CRITERIA

          1. Patients aged 18 years or older;

          2. Patients with at least 2 years history of SARC prior to the study and mild to moderate
             asthma (GINA criteria 2 and 3) inadequately controlled on inhaled corticosteroids and
             in whom "as-needed" short acting beta-agonists provide inadequate clinical control;

          3. Forced expiratory volume at one second (FEV1) > 70% of the predicted normal value
             demonstrable at least 6 hours after last short acting β-2 agonist use or 12 hours
             after last long acting β-2 agonist (LABA) use;

          4. Nasal Symptoms Score (NSS) at baseline ≥ 3. Baseline NSS will be defined as the mean
             of the 6 last assessments of the patients' diary (3 last days before randomization);

          5. Positive results of skin prick test on at least one seasonal allergen within the last
             3 years;

          6. Patients who provided a signed written informed consent form;

          7. Patients who are able and willing to complete web-based Patient's Diary;

          8. Patients who agree to maintain consistency in their surroundings throughout the study
             period;

          9. Women of childbearing potential (WOCBP) including peri-menopausal women who have had a
             menstrual period within 1 year have to have a negative pregnancy test. Results have to
             be available until the Visit 2 and negative for the patient to be entered in the
             study.

         10. WOCBP have to use an effective method of birth control throughout the study period and
             for 4 weeks after study completion (defined as a method which results in a failure
             rate of less than 1% per year) such as:

               -  combined (estrogen and progestogen containing) hormonal contraception associated
                  with inhibition of ovulation (oral, intravaginal, transdermal)

               -  progestogen-only hormonal contraception associated with inhibition of ovulation
                  (oral, injectable, implantable)

               -  intrauterine device (IUD)

               -  intrauterine hormone-releasing system (IUS)

               -  bilateral tubal occlusion

               -  vasectomised partner (provided that partner is the sole sexual partner of the
                  trial participant and that the vasectomised partner has received medical
                  assessment of the surgical success)

               -  sexual abstinence In each case of delayed menstrual period (over one month
                  between menstruations) confirmation of absence of pregnancy is strongly
                  recommended. This recommendation also applies to WOCBP with infrequent or
                  irregular menstrual cycles.

        EXCLUSION CRITERIA

          1. Patients with hypersensitivity to any component of the study medications;

          2. Patients with non-allergic rhinoconjunctivitis (e.g. vasomotor, infectious,
             drug-induced);

          3. Presence of nasal polyps or any clinically important nasal anomaly;

          4. History of acute and/or chronic sinusitis within 30 days of Visit 2;

          5. History of eye surgery within 3 months of Visit 2;

          6. History of intranasal surgery within 3 months of Visit 2;

          7. Immunotherapy within 6 months prior to Visit 1;

          8. Upper respiratory infections including cold and systemic infections within 3 weeks of
             Visit 2;

          9. Patients with moderate to severe renal impairment and taking P-gp inhibitors (e.g.
             ketoconazole, erythromycin, cyclosporine, ritonavir, diltiazem) within 7 days prior to
             the first dose of study medication;

         10. Patients requiring daily "controller" medications with cromolyn-type drugs or
             leukotriene antagonists;

         11. Patient required daily "controller" medication with Inhaled corticosteroids (ICS) or
             LABA at medium /high dosage defined by GINA criteria;

         12. Patients with clinically important (based on principal investigator's judgment)
             hepatic impairment;

         13. Patients with severe concomitant disease (based on principal investigator's judgment)
             that could interfere with treatment response;

         14. Patients with QT syndrome;

         15. Patients with Galactose intolerance, Lapp lactase deficiency or glucose- galactose
             malabsorption;

         16. Pregnant or breast-feeding women;

         17. Patients with a mental condition rendering the subject unable to understand the
             nature, scope and possible consequences of the study (based on principal
             investigator's judgment);

         18. Patients who had a recent history (within previous 12 months) of drug addiction or
             alcohol abuse based on Principal investigator's judgment ;

         19. Patients participating in or having participated in another clinical trial within the
             previous three months;

         20. Patients unable to take relief medications due to contraindications or intolerance;

         21. Patients who are taking or have taken any of the following medications prior to
             randomisation in the study and have not complied with the specified washout period:

               -  Antihistaminic drugs or montelukast (7 days)

               -  Systemic or intranasal corticosteroids (4 weeks)

               -  Delayed-release corticosteroids (3 months)

               -  Ketotifen (2 weeks)

               -  Macrolides antibiotics and imidazolic antifungals (systemic)(7 days)

               -  Anticholinergics (7 days)

               -  Drugs with antihistamine properties (phenothiazine) (7 days)

               -  Intranasal and systemic decongestants (3 days)

               -  Lodoxamide (7 days)

         22. Patients who will be operating heavy machinery or need to drive motor vehicles as an
             essential part of their profession.

         23. Patients who are planning to travel outside the study area during the course of the
             study.