| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of acute viral rhinosinusitis |
| Behandlung von akuter viraler Rhinosinusitis |
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| E.1.1.1 | Medical condition in easily understood language |
| Treatment of acute viral rhinosinusitis |
| Behandlung von akuter viraler Rhinosinusitis |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
| 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 |
Primary objective:
To evaluate the efficacy of Xylometazoline Hydrochloride (Xylo) + Sodium Hyaluronate (HA) nasal spray compared to Sodium Hyaluronate (HA) nasal spray and Xylometazoline Hydrochloride (Xylo) nasal spray in alleviating the symptoms of viral acute rhinosinusitis |
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| E.2.2 | Secondary objectives of the trial |
To evaluate:
Efficacy:
-efficacy of Xylo & HA nasal spray compared to HA nasal spray & Xylo nasal spray in alleviating symptoms of viral acute rhinosinusitis,
-treatment effect of Xylo & HA nasal spray on development of patient self-rated nasal symptom scores,
-treatment effect of Xylo & HA nasal spray on nasal mucosa efficacy measured by nasal rhinoscopy,
-treatment effect of Xylo & HA nasal spray on nasal patency,
-treatment effect of Xylo & HA nasal spray on olfactometry,
-treatment effect of Xylo & HA nasal spray treatment on mucociliary clearance,
-effect of Xylo & HA nasal spray treatment on actual duration of treatment;
-patient satisfaction with Xylo & HA nasal spray treatment
Safety & tolerability:
- to evaluate the safety of Xylo & HA nasal spray treatment in patients suffering from ARS
- to evaluate the safety of Xylo & HA nasal spray treatment on vital signs
- to evaluate tolerability of Xylo & HA nasal spray treatment |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patients aged from 12 – 65 years (at least 10% of the population should be from 12 to 17 years of age, valid for Bulgaria, Croatia and Poland) OR patients aged from 18-65 years (valid for Germany)
2. Presence of viral ARS, defined as a sudden onset of ≥2 of the following 4 symptoms: nasal congestion, nasal discharge (anterior or postnasal drip), facial pain or pressure, and reduction or loss of smell, one of which must be nasal congestion or nasal discharge
3. Symptom duration ≤72 hours before screening
4. Patient self-rated TNSS at screening ≥5 with nasal congestion score ≥2
5. For adults (≥18 years): Informed consent to participate in the trial provided in written form
6. For adolescents (≥12 - <18 years, valid for Bulgaria, Croatia and Poland): self-completed patient informed consent to participate in the trial and the informed consent from all parent(s)/ legal guardian(s) provided in written form
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| E.4 | Principal exclusion criteria |
1. History of hypersensitivity to Xylometazoline Hydrochloride or Sodium Hyaluronate or any excipient
2. Pregnancy or breastfeeding; females of child-bearing potential* (any female after menarche unless postmenopausal** for ≥12 months, or surgically sterilized) must have a negative pregnancy test at screening and be willing to use a highly effective method of contraception*** during the study and until the first period after the last dose of study medication
3. Presence of allergic rhinitis, non-allergic non-infectious rhinitis, including rhinitis sicca and rhinitis medicamentosa, or acute bacterial rhinosinusitis, as judged by the Investigator based on medical history and/or clinical presentation
4. History of chronic nasal obstruction, chronic rhinosinusitis, or recurrent acute rhinosinusitis (≥4 episodes of post-viral or bacterial rhinosinusitis) in previous 12 months
5. Acute respiratory infection in 4 weeks before screening
6. Patients with pathological condition of the nasal cavity such as significant septum deviation or nasal polyps
7. History of asthma bronchiale of any severity
8. History of immune defects including immunosuppression, immunopathies
9. Positive rapid antigen test for Corona virus disease 19 (COVID-19)
10. History of severe cardiovascular disease, long QT syndrome
11. History of trans-sphenoidal hypophysectomy or surgery exposing the dura mater
12. History of narrow-angle glaucoma, phaeochromocytoma
13. History of severe prostatic hypertrophy
14. Blood pressure at screening >140/90 mmHg for adult, or >120/80 mmHg for adolescent patients, or heart rate >100 bpm
15. Use of any topical or oral nasal decongestant within 24 hours before screening, or >3 doses of topical and/or oral decongestants in total within 3 days, or >9 doses in total within 2 weeks before screening
16. Use of intranasal drugs other than decongestants within 2 weeks before screening.
17. Use of systemic corticosteroids within 4 weeks before screening
18. Use of antibiotics within a period of 14 days (two weeks) before screening
19. Use of analgesic, antipyretic, cold or flu medication including OTC medication or herbal products within 8 h before screening
20. Use of monoamine oxidase inhibitors, tricyclic antidepressants, or ophthalmic corticosteroids, or systemic or ophthalmic antihistamines within 2 weeks before screening
21. Participation in another clinical trial within 3 months before screening, or over a period of 5 half-lives, or double duration of the biological effect of the investigational product received, whichever is longer
22. Patients whose participation in clinical trials is prohibited by local law.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Age-, sex-, and baseline-adjusted mean Area under the Curve of the Total Nasal Symptom Score determined based on six consecutive TNSS assessments after baseline assessment |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Demographic data at V1
TNSS Baseline measured at V1, than 6 consecutive entries of TNSS in patient diary (V1 to V3) |
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| E.5.2 | Secondary end point(s) |
- Age-, sex-, and baseline-adjusted mean Area under the Curve of the Total Nasal Symptom Score over the entire treatment course of up to 7 days.
- Change in adjusted mean TNSS and in scores for individual symptoms over the entire treatment period (age-, sex- and baseline-adjusted).
- Time to major improvement in symptoms (≥50% reduction in TNSS with no subsequent deterioration) and to resolution of symptoms (TNSS ≤1 with no subsequent deterioration).
- Change in mean rhinoscopy score (RS) between baseline (Day 1), Day 4 (+2 days) and Day 8 (±1 day). Change in mean individual characteristics of nasal mucosa redness, swelling of nasal mucosa and turbinates and nasal secretion between baseline (Day 1), Day 4 (+2 days) and Day 8 (±1 day).
- Change in Nasal Inspiratory Flow (PNIF) between baseline (Day 1), Day 4 (+2 days) and Day 8 (±1 day).
- Mean olfactometry score at baseline (Day 1), Day 4 (+2 days) and Day 8 (±1 day).
- Change in mean mucociliary transit time between baseline (Day 1) and on Day 4 (+2 days) and Day 8 (±1 day).
- Mean duration of treatment (time between the first and the last dose of study medication) and average total number of doses taken during the study.; Time to resolution of symptoms (TNSS ≤1 with no subsequent deterioration)
- Number (%) of patients satisfied with therapy on Day 8 (±1 day).
- Incidence of treatment-emergent AEs and treatment discontinuations due to AE during the study period.
Patient self-rating of the extent of nasal irritation (mean nasal irritation score, subscale of NSSS) at visit V1 after the first dose.
- Change in mean systolic blood pressure and heart rate at baseline (Day 1), before the first dose, within 20 min. after the first dose, and on Day 4 (+2 days) and Day 8 (±1 day).
-Mean Nasal Spray Sensory Scale (NSSS) score of the spray after the first dose (Day 1).
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
demographic data at V1
TNSS Baseline measured at V1, than entry in patient diary up to 7 days
Rhinoscopy score at V1 - V3
PNIF at V1 - V3
Olfactory score V1- V3
Saccharin Test V1- V3
Adverse events V1 - V3 and Follow-up Phone Call
NSSS at V1 |
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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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | 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 | 4 |
| 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 | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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