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

INTERVENTION: Trade Name: Sinupret extract Product Name: Sinupret extract coated tablets Pharmaceutical Form: Tablet Other descriptive name: DRY EXTRACT (3‐6:1) OF GENTIAN ROOT, PRIMULA FLOWERS, SORREL HERB, ELDER FLOWERS, VERVAINE HERB (1:3:3:3:3), EXTRACTING AGENT: ETHANOL 51% (M/M) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 160‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Chronic rhinosinusitis ; MedDRA version: 19.1 Level: LLT Classification code 10052106 Term: Rhinosinusitis System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Ear, nose and throat diseases [C09] PRIMARY OUTCOME: Main Objective: To assess the efficacy of the herbal medicinal product Sinupret extract versus placebo in the treatment of chronic rhinosinusitis (CRS) in adults. Primary end point(s): The primary efficacy endpoint; of this trial is MSSINV at V7. Secondary Objective: • To assess safety and tolerability of Sinupret extract versus placebo during the 16‐week treatment phase and the 4‐week follow‐up phase.; • To assess the effect of Sinupret extract versus placebo on selected inflammatory parameters in nasal secretions after 8‐ and 16‐week treatment periods compared to baseline in a subset of approximately 60 patients. Timepoint(s) of evaluation of this end point: Visit 7 (week 16). SECONDARY OUTCOME: Secondary end point(s): 1. MSSINV at V4, V5, and V6 ; 2. Major symptom score as assessed by the patient (MSSPAT) at V4, V5, V6, and V7 ; 3. Minimal MSSINV of all visits from V4 to V7 ; 4. Minimal MSSPAT of all visits from V4 to V7 ; 5. Investigator’s ratings of each individual CRS symptom (i.e. rhinorrhea [anterior], rhinorrhea [posterior], nasal congestion, headache, and facial pain/pressure) at V4, V5, V6, and V7 ; 6. Patient’s ratings of each individual CRS symptom (i.e. rhinorrhea [anterior], rhinorrhea [posterior], nasal congestion, headache, and facial pain/pressure) at V4, V5, V6, and V7 ; 7. 22‐Item Sino‐Nasal Outcome Test total score (SNOT‐22Total Score) as well as SNOT‐22 primary nasal score (SNOT‐22 PNS) and SNOT‐22 general quality of life score (SNOT‐22ALQ) at V4, V5, V6, and V7 ; 8. Total symptom severity assessed by the patient on a visual analogue scale (VAS) at V4, V5, V6, and V7 ; 9. Proportion of patients whose MSSINV and MSSPAT improved by =30%, =40%, =50%, =60% and =70% at V4, V5, V6, and V7. Responders are defined as patients who show at least an MSS improvement of =30% ; 10. Patients with permitted concomitant drug and non‐drug therapy (i.e. isotonic saline solution as nasal spray, nasal irrigation [nasal lavage], or ultrasonic nebulizer) for CRS ; 11. Patients with premature termination due to exacerbation of CRS symptoms ; 12. Investigator’s and patient’s overall assessment of efficacy at V4, V5, V6, and V7 ; 13. Absolute concentrations of selected inflammatory parameters (e.g. myeloperoxidase [MPO], eosinophil cationic protein [ECP], cytokines, a2‐macroglobulin, HMGB‐1, albumin) in nasal secretions collected at V2, V5 and V7 for a subset of approximately 60 patients in approximately 10 investigational sites in Germany ; 15. Pharmacoeconomic evaluation (utilization of health care resources) including: ; • Unscheduled or unforeseen visits to any physician due to CRS‐related symptoms ; • CRS‐related absenteeism from work (or other daily activities) INCLUSION CRITERIA: 1. Signed informed consent (IC) including data protection declaration ; 14. Change from baseline (V2) in the concentration of selected inflammatory parameters (e.g. MPO, ECP, cytokines, a2‐macroglobulin, HMGB‐1, albumin) in nasal secretions at V5 and V7 for a subset of approximately 60 patients in approximately 10 investigational sites in Germany ; • Patient’s Work Productivity and Activity Impairment, General Health (WPAI:GH) ratings at V4, V5, V6, and V7. The following validated endpoints will be analyzed: percentage of work time missed due to health, percentage of impairment while working due to health, percentage of overall work impairment due to health, and percentage of activity impairment due to health Timepoint(s) of evaluation of this end point: Visit 2 (baseline), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12), visit 7 (week 16). 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, o