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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02761252
Recruitment Status : Completed
First Posted : May 4, 2016
Results First Posted : July 12, 2019
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
Menarini International Operations Luxembourg SA

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

Condition or disease Intervention/treatment Phase
Seasonal Allergic Rhinoconjunctivitis Asthma Drug: Bilastine 20mg Drug: Montelukast 10mg Drug: Placebo Bilastine 20mg Drug: Placebo Montelukast 10mg Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 454 participants
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.

Primary Purpose: Treatment
Official Title: Bilastine and Montelukast in Patients With Seasonal Allergic Rhinoconjunctivitis and Asthma: Efficacy of Concomitant Administration - the SKY Study
Actual Study Start Date : April 13, 2016
Actual Primary Completion Date : November 24, 2016
Actual Study Completion Date : November 24, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Montelukast

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 Name: Robilas

Drug: Montelukast 10mg
Other Name: 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 Name: Robilas

Drug: Placebo Montelukast 10mg
Other Name: 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 Name: Montelukast

Drug: Placebo Bilastine 20mg
Other Name: Placebo Bilastine




Primary Outcome Measures :
  1. Change From Baseline With Montelukast+Bilastine Compared With Bilastine Monotherapy in SARC Symptoms [ Time Frame: 4 weeks of treatment (from baseline to 4 weeks of treatment) ]

    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.



Secondary Outcome Measures :
  1. Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in Asthma Control [ Time Frame: After 4 weeks of treatments ]

    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.


  2. Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNSS) [ Time Frame: After 4 weeks of treatment (from baseline) ]

    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.


  3. Change From Baseline With Montelukast + Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNNSS) [ Time Frame: After 4 weeks of treatment (from baseline) ]

    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.


  4. Usage of Relief Medication for SARC [ Time Frame: From baseline to 4 weeks of treatment ]
    Number of days without any relief medication for SARC

  5. Usage of Relief Medication for Asthma [ Time Frame: From baseline to 4 weeks of treatment ]
    Number of days without any relief medication for Asthma.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02761252


Locations
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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
Sponsors and Collaborators
Menarini International Operations Luxembourg SA
Investigators
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Study Director: Massimo Pistolesi, Prof AOUC Azienda Ospedaliero-Universitaria Careggi
Study Director: Oliviero Rossi, Prof AOUC Azienda Ospedaliero-Universitaria Careggi

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Responsible Party: Menarini International Operations Luxembourg SA
ClinicalTrials.gov Identifier: NCT02761252    
Other Study ID Numbers: MEIN/15/Bil-ARC/001
2015-004806-40 ( EudraCT Number )
First Posted: May 4, 2016    Key Record Dates
Results First Posted: July 12, 2019
Last Update Posted: July 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Menarini International Operations Luxembourg SA:
Bilastine
Montelukast
total symptom score
AQLQ
Additional relevant MeSH terms:
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Asthma
Conjunctivitis, Allergic
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Conjunctivitis
Conjunctival Diseases
Eye Diseases
Montelukast
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action