Clinical trial NCT02761252: Efficacy of Co-administration of Bilastine and Montelukast in Patients With SARC and Asthma
Official title: Bilastine and Montelukast in Patients With Seasonal Allergic Rhinoconjunctivitis and Asthma: Efficacy of Concomitant Administration - the SKY Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Seasonal Allergic Rhinoconjunctivitis
Asthma
Keywords: Bilastine
Montelukast
total symptom score
AQLQ
Lead sponsor: Menarini International Operations Luxembourg SA
Sponsor class: INDUSTRY
First posted: 2016-05-04
Enrollment: 454
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

Brief 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

Detailed description: The present study (SKY) was designed to show if once daily oral combination therapy with Montelukast 10 mg and Bilastine 20 mg is superior to monotherapy with Bilastine 20 mg in patients with Seasonal Allergic RhinoConjunctivitis (SARC) and comorbid mild to moderate asthma on total symptom scores (TSS) and if the combination therapy reflects an improvement in quality of life as assessed via the Asthma Quality of Life Questionnaire (AQLQ) over a longer time period when compared to monotherapies with Montelukast 10 mg and Bilastine 20 mg. Mild to moderate asthma was defined according to the criteria of the Global Initiative for Asthma, i.e., GINA criteria 2 and 3 (GINA, 2012). The study population included patients inadequately controlled on inhaled corticosteroids and in whom "as-needed" short acting beta-agonists provided inadequate clinical control.

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.

Primary outcomes:
measure: Change From Baseline With Montelukast+Bilastine Compared With Bilastine Monotherapy in SARC Symptoms
timeFrame: 4 weeks of treatment (from baseline to 4 weeks of treatment)
Secondary outcomes:
measure: Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in Asthma Control
timeFrame: After 4 weeks of treatments
measure: Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNSS)
timeFrame: After 4 weeks of treatment (from baseline)
measure: Change From Baseline With Montelukast + Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNNSS)
timeFrame: After 4 weeks of treatment (from baseline)
measure: Usage of Relief Medication for SARC
timeFrame: From baseline to 4 weeks of treatment
measure: Usage of Relief Medication for Asthma
timeFrame: From baseline to 4 weeks of treatment
Other outcomes:
Locations:
city: Cakovec
country: Croatia
city: Rijeka
country: Croatia
city: Zagreb
country: Croatia
city: Brno
country: Czechia
city: Ostrava Hrabuvka
country: Czechia
city: Teplice
country: Czechia
city: Dreieich
country: Germany
city: Heidelberg
country: Germany
city: Catania
country: Italy
city: Florence
country: Italy
city: Modena
country: Italy
city: Pavia
country: Italy
city: Verona
country: Italy
city: Riga
country: Latvia
city: Bialystok
country: Poland
city: Bielsko-Biala
country: Poland
city: Gdansk
country: Poland
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Nowy Duninow
country: Poland
city: Poznan
country: Poland
city: Rzeszow
country: Poland
city: Tarnow
country: Poland
city: Wroclaw
country: Poland
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Cluj Napoca
country: Romania
city: Ploieşti
country: Romania
city: Bardejov
country: Slovakia
city: Levice
country: Slovakia
Study officials:
affiliation: AOUC Azienda Ospedaliero-Universitaria Careggi
name: Massimo Pistolesi, Prof
role: STUDY_DIRECTOR
affiliation: AOUC Azienda Ospedaliero-Universitaria Careggi
name: Oliviero Rossi, Prof
role: STUDY_DIRECTOR
References: