Sinupret Extract Coated Tablets in Chronic Rhinosinusitis

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Clinical Trial to Assess Efficacy and Safety of the Herbal Medicinal Product Sinupret Extract Coated Tablets in Patients With Chronic Rhinosinusitis

To assess the efficacy of the herbal medicinal product Sinupret extract versus placebo in the treatment of chronic rhinosinusitis (CRS) in adults.

The aim of the present double-blind, placebo-controlled, parallel-group, randomized, phase III clinical trial is to assess the efficacy, safety, and tolerability of Sinupret extract (3 x 160 mg = 480 mg daily) taken for up to 16-weeks compared with placebo in the treatment of chronic rhinosinusitis (CRS) in adults. In addition, in an exploratory approach to identify potential pharmacological modes of action underlying the expected treatment benefit, the anti-inflammatory activity of Sinupret extract will be assessed in a subset of CRS patients.

Inclusion Criteria:

1. Signed informed consent (IC) including data protection declaration

2. Male and female outpatients aged ≥18 and ≤75 years

   Women will be considered for inclusion if they are not pregnant (as confirmed by urine pregnancy test at V1 and V2), not breastfeeding, or if they are surgically sterile (have had a documented bilateral oophorectomy and/or hysterectomy) or if menopause is ensured (at least 12 months without menstrual bleeding). Women of childbearing potential must use a highly effective (failure rate less than 1% per year, i.e. Pearl Index <1) method of contraception 2 weeks prior to trial inclusion and during the screening/treatment period of the clinical trial (e.g. vasectomized partner, sexual abstinence - the lifestyle of the female has to be such that there is complete abstinence from intercourse from 2 weeks prior to the first dose of trial medication until at least 72 hours after treatment - implants, injectables, combined oral contraceptives, or hormonal intrauterine devices).

3. Diagnosis of bilateral CRS without nasal polyps confirmed by:

   • Nasal endoscopy during the screening phase to confirm inflammation, mucopurulent discharge, and/or edema/mucosal obstruction primarily in middle meatus without nasal polyps being present
   • At the discretion of the investigator, results from a historic imaging diagnostic, i.e. computer tomography (CT), digital volume tomography (DVT), or magnetic resonance tomography (MRT) (before screening and not older than 24 months, not taken during acute exacerbation), which will be considered additionally for confirmation of bilateral involvement of middle meatus and paranasal sinuses without resolution of symptoms (mucosal changes within the ostiomeatal complex and/or sinuses)

4. Bilateral CRS characterized by:

   • Presence of CRS symptoms for >52 weeks prior to enrolment (V1) as documented in the medical file of the patient
   • Major Symptom Score (MSS) ≥10 at V1 and V2 as assessed by the investigator (MSS INV), and rhinorrhea (anterior or posterior) and pain (facial pain or headache) each of at least moderate intensity (score ≥2)

Exclusion Criteria:

1. Sinus surgery within the last 2 years (solitary sinus puncture is allowed)
2. Inferior turbinate reduction (by surgery or other methods) within the last 3 months
3. Presence or history of uni- or bilateral nasal polyps
4. Moderate to severe co-morbid asthma, including allergic asthma
5. Cystic fibrosis
6. Perennial (e.g. patients with clinical symptoms of allergic rhinitis against house dust/mite antigen) or seasonal allergic rhinitis
7. Rhinitis medicamentosa (drug induced rhinitis)
8. Aspirin-exacerbated respiratory disease (aspirin sensitivity)
9. Dentogenic sinusitis or otherwise unilateral sinusitis
10. Presence of anatomical deviations of the nasal septum that significantly impair nasal and paranasal ventilation/airflow
11. Known hypersensitivity to trial medication or excipients
12. Rare hereditary problems of fructose intolerance, galactose intolerance, lactase deficiency, glucose-galactose malabsorption, or sucrase- isomaltase insufficiency
13. Signs or symptoms of acute bacterial sinusitis (e.g. fever >38.5°C, orbital complications, severe unilateral frontal headache, or toothache)
14. Treatment with antihistamines within 4 weeks prior to V1
15. Treatment with 2-3.5% hypertonic saline solution within 2 weeks prior to V1
16. Treatment with systemic or nasal antibiotics or corticosteroids within 4 weeks prior to V1
17. Treatment with decongestant preparations (α-sympathomimetics), analgesics (including systemic non-steroidal inflammatory drugs [NSAIDs], including paracetamol), mucolytics/secretolytics, or alternative medicine preparations for treatment of common cold-like symptoms or with immunomodulating properties within 7 days prior to V1
18. Peptic ulcer
19. Gastritis
20. Other diseases within 5 years prior to V1 that, in the opinion of the investigator, disqualifies the patient for trial enrolment (e.g. liver or kidney disease, severe somatopathic, neurological and/or psychiatric diseases, history of malignancy, alcohol or drug abuse, or immunodeficiency)
21. Parallel participation in another clinical trial, participation in a different trial within less than 6 weeks prior to trial entry, or previous randomization into this clinical trial
22. Known to be, or suspected of being unable to comply with the clinical trial protocol (CTP) that in the opinion of the investigator disqualifies the patient for trial enrolment (e.g. no permanent address, known to be non-compliant, or presenting an unstable psychiatric history)
23. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope, and possible impact of the clinical trial
24. Patients in custody by juridical or official order
25. Patients who have difficulties in understanding the local language in which the patient information (PI) is given
26. Patients who are members of the staff of the investigational site, staff of the sponsor or involved CRO, the investigator him/herself or close relatives