Efficacy of Co-administration of Bilastine and Montelukast in Patients With SARC and Asthma (SKY)

Bilastine and Montelukast in Patients With Seasonal Allergic Rhinoconjunctivitis and Asthma: Efficacy of Concomitant Administration - the SKY Study

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

Study Overview

• Status: Completed
• Conditions: Asthma; Seasonal Allergic Rhinoconjunctivitis
• Intervention / Treatment: Drug: Bilastine 20mg; Drug: Montelukast 10mg; Drug: Placebo Montelukast 10mg; Drug: Placebo Bilastine 20mg

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.

• Study Type: Interventional
• Enrollment (Actual): 454
• Phase: Phase 4

Contacts and Locations

Study Locations

• Croatia
  • Cakovec, Croatia
  • Rijeka, Croatia
  • Zagreb, Croatia
• Czechia
  • Brno, Czechia
  • Ostrava Hrabuvka, Czechia
  • Teplice, Czechia
• Germany
  • Dreieich, Germany
  • Heidelberg, Germany
• Italy
  • Catania, Italy
  • Florence, Italy
  • Modena, Italy
  • Pavia, Italy
  • Verona, Italy
• Latvia
  • Riga, Latvia
• Poland
  • Bialystok, Poland
  • Bielsko-Biala, Poland
  • Gdansk, Poland
  • Katowice, Poland
  • Krakow, Poland
  • Lodz, Poland
  • Lublin, Poland
  • Nowy Duninow, Poland
  • Poznan, Poland
  • Rzeszow, Poland
  • Tarnow, Poland
  • Wroclaw, Poland
• Romania
  • Brasov, Romania
  • Bucharest, Romania
  • Cluj Napoca, Romania
  • Ploieşti, Romania
• Slovakia
  • Bardejov, Slovakia
  • Levice, Slovakia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bilastine+montelukast; Bilastine 20 mg, 10 blister containing 10 tablets + Montelukast 10 mg, 10 blister containing 10 film coated tablets each for treatment	Drug: Bilastine 20mg; Other Names: Robilas; Drug: Montelukast 10mg; Other Names: Montelukast
Active Comparator: Bilastine+placebo montelukast; Bilastine 20 mg, 10 blister containing 10 tablets + Placebo Montelukast, 10 blister containing 10 film coated tablets each.	Drug: Bilastine 20mg; Other Names: Robilas; Drug: Placebo Montelukast 10mg; Other Names: Placebo Montelukast
Active Comparator: Montelukast+placebo bilastine; Placebo Bilastine, 10 blister containing 10 tablets + Montelukast 10 mg, 10 blister containing 10 film coated tablets each.	Drug: Montelukast 10mg; Other Names: Montelukast; Drug: Placebo Bilastine 20mg; Other Names: Placebo Bilastine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline With Montelukast+Bilastine Compared With Bilastine Monotherapy in SARC Symptoms	To demonstrate that concomitant administration of montelukast and bilastine is superior to bilastine monotherapy in SARC symptoms, as assessed by Total Symptoms Scores (TSS) after 4 weeks of treatment. Total Symptoms Scores (TSS) assesses nasal (nasal congestion, rhinorrhea, nasal itching, sneezing) and non nasal symptoms (ocular redness, ocular itching, tearing) of rhinoconjuctivits. Each of the 7 symptoms is scored from 0 (absent) to 3 (severe) as follows: 0 (absent) Symptom not present; 1 (mild) Symptom is clearly present but easily tolerated, a nuisance, minimal awareness; 2 (moderate) Symptom is bothersome but tolerable, does not interfere with daily activities or sleep; 3 (severe) Symptom is hard to tolerate and interferes with daily activities or sleep. TSS assessment comprises of scoring (0-3) of all 7 above mentioned symptoms. Final TSS scores is in a range from 0-21.	4 weeks of treatment (from baseline to 4 weeks of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in Asthma Control	To evaluate the efficacy of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies in asthma control, as assessed by Asthma Quality of Life Questionnaire (AQLQ) after 4 weeks. The AQLQ was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (17-70 years) with asthma. Each of the 32 questionnaire's items will be scored on a 7-point scale (where 7 means "not impaired at all" and 1 means "severely impaired"). The overall AQLQ score is the mean of all 32 responses (https://www.qoltech.co.uk/aqlq.html). The change in AQLQ score from baseline to 4 weeks after treatment - AQLQ score at baseline for patients with both available values has been the secondary endpoint.	After 4 weeks of treatments
Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNSS)	To evaluate the efficacy of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies in daytime symptoms of SARC, as assessed by Daytime Nasal Symptom Score (DNSS) after 4 weeks of treatment. Daytime Nasal Symptom Score (DNSS) is the average of individual scores of nasal congestion, rhinorrhea, nasal itching, sneezing of rhinoconjuctivits. Each of the 4 symptoms is scored from 0 (absent) to 3 (severe) as follows: 0 (absent) Symptom not present; 1 (mild) Symptom is clearly present but easily tolerated, a nuisance, minimal awareness; 2 (moderate) Symptom is bothersome but tolerable, does not interfere with daily activities or sleep; 3 (severe) Symptom is hard to tolerate and interferes with daily activities or sleep. DNSS assessment comprises of scoring (0-3) of all 4 above mentioned symptoms. Final DNSS scores is in a range from 0-12.	After 4 weeks of treatment (from baseline)
Change From Baseline With Montelukast + Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNNSS)	To evaluate the efficacy of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies in daytime symptoms of SARC, as assessed by Daytime Non Nasal Symptom Score (DNNSS) after 4 weeks of treatment. Daytime Non Nasal Symptom Score (DNSS) is the average of individual scores of ocular redness, ocular itching and tearing of rhinoconjuctivits. Each of the 3 symptoms is scored from 0 (absent) to 3 (severe) as follows: 0 (absent) Symptom not present; 1 (mild) Symptom is clearly present but easily tolerated, a nuisance, minimal awareness; 2 (moderate) Symptom is bothersome but tolerable, does not interfere with daily activities or sleep; 3 (severe) Symptom is hard to tolerate and interferes with daily activities or sleep. DNNSS assessment comprises of scoring (0-3) of all 3 above mentioned symptoms. Final DNNSS scores is in a range from 0-9.	After 4 weeks of treatment (from baseline)
Usage of Relief Medication for SARC	Number of days without any relief medication for SARC	From baseline to 4 weeks of treatment
Usage of Relief Medication for Asthma	Number of days without any relief medication for Asthma.	From baseline to 4 weeks of treatment

Collaborators and Investigators

• Sponsor: Menarini International Operations Luxembourg SA
• Investigators: Study Director: Massimo Pistolesi, Prof, AOUC Azienda Ospedaliero-Universitaria Careggi; Study Director: Oliviero Rossi, Prof, AOUC Azienda Ospedaliero-Universitaria Careggi

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2016
• Primary Completion (Actual): November 24, 2016
• Study Completion (Actual): November 24, 2016

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimate): May 4, 2016

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Montelukast; Bilastine; total symptom score; AQLQ
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Eye Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Conjunctivitis; Conjunctival Diseases; Asthma; Conjunctivitis, Allergic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: MEIN/15/Bil-ARC/001; 2015-004806-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No