E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Seasonal allergic rhinitis with and without mild to moderate bronchial asthma |
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E.1.1.1 | Medical condition in easily understood language |
Seasonal alergic rhinitis with or without asthma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001723 |
E.1.2 | Term | Allergic rhinitis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 therapeutic superiority of the test FDC product (rupatadine and motelukast) over rupatadine monotherapy in seasonal allergic rhinitis patients with and without mild to moderate bronchial asthma inadequately controlled. |
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E.2.2 | Secondary objectives of the trial |
To assess efficacy and safety parameters of the fix dose combination and to collect additional data that supports superiority in terms of efficacy versus monotherapy with rupatadine |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent in accordance with applicable regulatory requirements. 2. Male and female outpatients aged 18 or more with at least 1-year history of SAR inadequately controlled and in need of alternative treatments as per the treating physicians with or without mild to moderate allergic bronchial asthma. 3. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use methods of contraception (barrier methods and oral contraceptives) throughout the study visits. 4. Positive skin prick test (wheal +/- 3 mm larger than the diluent control) to at least one seasonal allergen specific to their geographical location. 5. Evaluation of four nasal symptoms scores (T4NSS)measured as reflective way (12 hours apart in the morning and evening periods) at screening. 6. Adequate wash-out to baseline if patients are taking any of the some medications. Nasal corticosteroids are the unique medication allowed in this period. Additional inclusion criteria for patients with asthma 1. History of asthma for at least 6 months before screening. 2. Adult patients with mild-to-moderate asthma partially controlled by beclomethasone dipropionate or equivalent (budesonide ≤400 μg/d, ciclesonide ≤160 μg/d, fluticasone ≤250 μg/d or mometasone ≤400 μg/d) according to GINA guidelines (alone or in combination with long term beta2-adrenergic bronchodilators). |
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E.4 | Principal exclusion criteria |
1. Active acute or chronic pulmonary disorder, acute sinus disease that have not resolved within 1 week (active hay fever and AR symptoms are allowed), and upper respiratory tract infection within 3 weeks, emergency department treatment of asthma within 1 month, and hospitalization for asthma within 3 months before the randomization visit. 2. Bronchial asthma patients who receive treatment with inhaled corticosteroids (ICS), alone or in combination with short and/or long term β2-adrenergic bronchodilators, at dosage >500 μg beclomethasone dipropionate or equivalent (budesonide >400 μg/d, ciclesonide >160 μg/d, fluticasone >250 μg/d and mometasone >400 μg/d) within 2 weeks. 3. Daily treatment with montelukast within 7 days prior to randomization, cetirizine and bilastine (3 days), levocetirizine (2 days), loratadine, desloratadine, rupatadine and any other oral H1 antihistaminic not listed above (6 days), systemic corticosteroids (28 days), ketotifen (2 weeks), macrolides and imidazolic antifungals (7 days), anticholinergic drugs (7 days), topical antihistaminic drugs (e.g. nasal or drops) (2 days), drugs with antihistamine properties (e. g. phenothiazine) (6 days), intranasal/systemic decongestants and eye drops (3 days). 4. Patients suffering from non-allergic rhinitis (e.g., vasomotor, infectious, or drug-induced rhinitis). 5. Patients who had undergone nasal surgery in the previous 6 months and patients with nasal polyps, significant deviation of the nasal septum, acute or chronic sinusitis. 6. Clinically relevant respiratory tract malformations. 7. Recent nasal biopsy (within 2 months). 8. Nasal trauma; nasal surgery; atrophic rhinitis; rhinitis medicamentosa (within 2 months). 9. Antibiotic use for acute conditions within 2 weeks of screening. 10. History of QT prolongation and/or torsade de pointes, including congenital long QT syndromes, history of cardiac arrhythmias. 11. Smokers who report consuming more than 10 cigarettes per day. 12. History or presence of an immunodeficiency disorder. 13. Hypersensitivity to any beta-agonist, sympathomimetic drug, leukotriene antagonist. 14. Patients with a known history of HIV, hepatitis B or hepatitis C infection. 15. Any abnormal laboratory value of clinical relevance. 16. Pregnant or nursing mother. 17. Current evidence of any clinically significant disease of the hematopoietic, gastrointestinal, cardiovascular, pulmonary, or any other systems that might hinder the subject participation. 18. Abuse or dependency of alcohol, narcotics, opioids or any other addictive substances. 19. Patients that participated in any type of clinical study within the last month of the screening date. 20. Unsuitability for enrollment otherwise as decided by the investigator. 21. The drug products contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take these drugs. 22. Patients who had received immunotherapy for less than 6 months (unless on a stable dose within the prior month, and none within 24 hours before any study visit) or any Central Nervous System (CNS) acting agents (including antidepressants, sedatives, anxiolytics, hypnotics, opioids or neuroleptics) at any time. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main efficacy endpoint will be the change in the T4NSS on the 28 day of treatment (PDC reflective 12 hours symptoms, every day including the visit days with the investigator) compared with Day 0.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of treatment (day 28±2)
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E.5.2 | Secondary end point(s) |
• Change in the total score of patient symptoms (T7SS) on the 28 day of treatment (reflective evaluation) compared with Day 0. • Change in the total score of non-nasal patient symptoms (T3NNSS) on the 28 day of treatment (reflective evaluation) compared with Day 0. • Change in the daily score for each symptom (DSS) on the 28 day of treatment (reflective evaluation) compared with Day 0. • Mean value of the daily total score of symptoms (mTSS). • Time to beginning of action (first week). • Percentage of patients requiring rescue medication. • Assessment of instantaneous overall effectiveness (both patient and investigator) • Improvement in quality of life (Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ]) evaluated. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of treatment (day 28±2) |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |