| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| acute, uncomplicated rhinosinusitis |
| akute, unkomplizierte Rhinosinusitis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Inflammation of the nasal and paranasal sinus |
| Entzündung der Nasenschleimhaut und Nasennebenhöhlen |
|
| 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 |
| The objective of the present clinical trial is to assess the efficacy, safety and tolerability of Sinusitis Hevert SL, compared to placebo, in adult patients with uncomplicated, acute rhinosinusitis |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed informed consent
2. Male and female outpatients, aged ≥18 and ≤75 years
3. Diagnosis of acute, uncomplicated (or recurrent acute) rhinosinusitis
– characterized by Major Rhinosinusitis Symptom Score (MRSSinv) ≥ 8 and ≤ 15 points
–individual score for facial pain/pressure (on bending) ≥ 1 (mild) and ≤ 2 (moderate)
– with presence of symptoms ≤3 days prior to inclusion
Out of the 5 main rhinosinusitis symptoms, at least 3 must be present. Among these, the presence of nasal congestion and facial pain / pressure (on bending) is mandatory.
4. Women of childbearing potential: willingness to use contraception methods |
|
| E.4 | Principal exclusion criteria |
a) Diseases
1. Chronic rhinosinusitis (i.e. all forms and causes of persistent chronic rhinosinusitis)
2. Polyposis nasi, recent history
3. Infection of dental origin in the maxilla
4. Cystic fibrosis, recent history
5. Anatomical deviations of the nasal septum that significantly impair nasal and paranasal ventilation / air flow
6. Acute symptoms of a known allergic rhinitis
7. History of smoking within the last two years prior to study enrolment or current smoking habits
8. Patients with asthma
9. Known hypersensitivity to study medication or excipients (asteraceae, lactose, allergy to bee venom, etc.)
10. Underlying diseases leading to a significant immune deficiency
11. Signs or symptoms of bacterial sinusitis requiring antibiotic treatment (e.g. fever >38.3°C, orbital complications, severe unilateral frontal headache or toothache)
12. Patients with progressive auto-immune diseases, tuberculosis, leukemia or leukemia-like diseases, multiple sclerosis, inflammatory diseases of the connective tissues, rheumatoid arthritis, Lupus erythematodes, HIV infection or other chronic viral diseases
13. Patients with untreated/unstable thyroid gland disorder (treatment should not include iodine supplementation)
14. Pre-menopausal women (last menstruation ≤ 1 year prior to informed consent) who:
- are nursing or pregnant,
- or are of child-bearing potential and are not practicing an acceptable meth-od of birth control, or do not plan to continue using this method throughout the study. Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, double barrier methods, sexual abstinence and vasectomised partner.
15. Severe diseases of liver or kidney
16. Severe somatopathic, neurological and / or psychiatric diseases
17. Patients with malignant growth processes or cancer treatment within the last two years prior to study inclusion.
18. History of alcohol or drug abuse
b) Medication
1. Treatment with systemic or nasal antibiotics or nasal or systemic corticosteroids within the last 4 weeks prior to study inclusion
2. Treatment with alternative medicine preparations (homeopathical and phytotherapeutical drugs) for treatment of common cold like symptoms or with immunomodulating properties (such as Echinacea), within the last 7 days prior to study inclusion
3. Treatment with decongestant (alpha-sympathomimeticson the day of study inclusion within 5 hours prior to screening and during the study)
4. Chronic use of decongestant remedies
5. Treatment with immunosuppressive medication 8 weeks prior to study inclusion and during the study for any condition
6. Systemic antiviral treatment such as aciclovir; zanamivir, or oseltamivir within 30 days prior to study inclusion
7. Patients requiring antibiotic treatment for any condition at study entry
c) General
1. Parallel participation in any other clinical study or participation in another study within less than 6 weeks prior to study inclusion, or previous participation in this same study
2. Legal incapacity and / or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the study
3. Patients in custody by juridical or official order
4. Patients who have difficulties in understanding the language (German) in which the patient information is given
5. Patients who are employees of a trial center, the CRO, the sponsor or its authorised representatives or are relatives either of the study site staff, the CRO staff, the sponsor staff or its authorised representatives |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The first primary endpoint of the clinical trial is the rate of responders which occur between baseline and V4. A response is defined as stable reduction of MRSSpat (sum of 5 main rhinosinusitis symptoms daily assessed by the patient) by at least 50%, i.e. reduction by at least 50% and no subsequent change from baseline > –50% up to treatment termination.
The second primary endpoint of the clinical trial is the rate of remissions which occur between baseline and V4. A remission is defined as complete disappearance of all 5 main rhinosinusitis symptoms with no subsequent reoccurrence of any symptom up to treatment termination. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| continuous between baseline and V4 |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
- Time to response
- Time to remission
- Time to improvement in the individual MRSSpat symptoms (in case of positive baseline value)
- Time to disappearance in the individual MRSSpat symptoms (in case of positive baseline value)
- Change in the overall MRSSinv (sum of 5 main rhinosinusitis symptoms assessed by the investigator) at V2, V3 and V4, as well as in the time course of the study
- Change in the overall MRSSinv (sum of the remaining symptoms) between baseline and V2, V3, and V4, as well as in the time course of the study
- Change in the individual MRSSinv symptoms, at V2, V3, and V4, as well as in the time course of the study
- Change in the SNOT-20 GAV, in the Overall Score (OS) as well as in the sub scores PNS (Primary Nasal Symptoms), SRS (Secondary Rhinogenous Symptoms, and Quality of Life Score (GQoL), assessed by the patient between baseline and V2, V3 and V4
- Change in the SNOT-20 GAV, 5 most important symptoms, assessed by the patient between baseline and V2, V3 and V4
- Change in the SNOT-20 GAV, individual symptoms, assessed by the patient between baseline and V2, V3 and V4
- Change in the assessment of health status with respect to ARS by patient using a Visual Analogue Scale (VASpat) between baseline and V2, V3, and V4
- Change in the assessment of the patient’s health status with respect to ARS by the investigator using a Visual Analogue Scale (VASinv) between baseline and V4
- General assessment of efficacy assessed by the investigator (on a 4-point rating scale) at each visit from V2 to V4
- Use of antibiotics / rescue medication
Safety:
- Rate and intensity of AEs
- Withdrawal due to AEs
- Clinically relevant new or worsening findings in physical examination as reported as adverse event
- Changes from baseline in physical examination and vital signs (blood pressure, pulse rate, body temperature)
- VAS for treatment tolerability (VAStol-pat) by patient at each visit (V2, V3 and V4)
- VAS assessment of tolerability by investigator at V4 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| 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
|
The end of the trial is defined as the date of the last close-out visit (COV).
The whole trial is considered as terminated when all participating trial sites are closed and it is assured that all queries are answered and the data base is clean.
|
|
| 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 | 8 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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