E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Seasonal allergic rhinoconjunctivitis and asthma |
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E.1.1.1 | Medical condition in easily understood language |
Allergic rhinitis or hay fever and asthma |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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) at the end of treatment.
To evaluate the efficacy of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies in SARC symptoms, as assessed by TSS in the first 3 weeks of treatment.
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) and Daytime Non Nasal Symptom Score (DNNSS) after 1, 2, 3 and 4 weeks of treatment.
To evaluate the safety of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies.
To evaluate usage of relief medication for SARC and asthma
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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) 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 use;
4) 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 had to have a negative pregnancy test. Results had to be available on 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.
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E.4 | Principal exclusion criteria |
1) Patients with hypersensitivity to any component of the study medications;
2) Patients with non-allergic rhinoconjunctivtis (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 2;
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 from 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 ICS or LABA/ICS at medium /high dosage (as defined in GINA table attached);
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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in the Total Symptoms Score (TSS) from baseline and after 4 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Mean change in the Total Symptoms Score (TSS) from baseline and after 4 weeks of treatment. |
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E.5.2 | Secondary end point(s) |
Mean change in the Asthma Quality of Life Questionnaire Score (AQLQ) from baseline to the end of treatment;
Mean change in TSS, DNSS and DNNSS from baseline and after 1 week of treatment;
Mean change in TSS, DNSS and DNNSS from baseline and after 2 weeks of treatment;
Mean change in TSS, DNSS and DNNSS from baseline and after 3 weeks of treatment;
Mean change in DNSS and DNNSS from baseline and after 4 weeks of treatment;
Assessment of AEs;
Number of days without any relief medication for SARC
Number of days with 1 daily dose of relief medication for SARC;
Number of Days with 2 or more daily doses of reiel medication for SARC
Number of days without any relief medication for asthma;
Number of days with 1 daily dose of relief medication for asthma;
Number of Days with 2 or more daily doses of reiel medication for asthma |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
study days Day 1, Day29 +/- 4 days after Day 1; day 85 +/- 4 days after Day 1 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |