Prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial to evaluate the efficacy and safety of cineole vs. placebo in the treatment of acute non-purulent rhinosinusitis

INTERVENTION: Product Name: Cineole 200 mg, Sinupan forte Pharmaceutical Form: Gastro‐resistant capsule, soft INN or Proposed INN: 1,8‐cineole CAS Number: 470‐82‐6 Other descriptive name: CINEOLE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Gastro‐resistant capsule, soft Route of administration of the placebo: Oral use CONDITION: Acute, non‐purulent 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: English The objective of this study is to evaluate the efficacy and tolerability of cineole in comparison to placebo, based on the clinical success in patients with acute non‐purulent rhinosinusitis with an appearance of sinusitis symptoms not later than 5 days; ; Primary aim:; To establish the efficacy of cineole by demonstrating superiority compared to placebo by evaluating the change (difference) of the Major symptom score (MSS):; 1. from baseline to day 7 (End‐of‐treatment, V3); 2. from baseline to day 3 (Interim, V2), (in case of significant result of 1).; Primary end point(s): To establish the efficacy of cineole by demonstrating superiority compared to placebo by evaluating the change (difference) of the Major symptom score (MSS) ; 1. from baseline (V1) to day 7 (End‐of‐treatment, V3) ; 2. baseline (V1) to day 3 (Interim visit, V2) (in case of significant results of 1); Secondary Objective: – Change (difference) of the Major Symptom Score (MSS) from baseline (V1) to visit V4.; – Response to treatment defined as improvement of MSS by >=50% at day 7 (V3) as compared to baseline.; – Response to treatment defined as improvement of MSS by >=50% at day 3 (V2) as compared to baseline.; – Safety evaluation by comparison of the incidence of adverse events in the treatment groups.; – Number of drop‐out patients requiring alternative therapy with antibiotics at interim visit at day 3. Timepoint(s) of evaluation of this end point: Day 7 (EOT, V3); ; Day 3 (Interim visit, V2) SECONDARY OUTCOME: Secondary end point(s): 1) Change (difference) of the Major Symptom Score (MSS) from baseline (V1) to visit V4. ; 2) Response to treatment defined as improvement of MSS by >=50% at day 7 (V3) as compared to baseline. ; 3) Response to treatment defined as improvement of MSS by >=50% at day 3 (V2) as compared to baseline. ; 4) Safety evaluation by comparison of the incidence of adverse events in the treatment groups. ; 5) Number of drop‐out patients requiring alternative therapy with antibiotics at interim visit at day 3. Timepoint(s) of evaluation of this end point: 1) Day 14 (V4) ; 2) Day 7 (V3) ; 3) Day 3 (V2) ; 4) Day 14 (V4) ; 5) Day 3 (V2) INCLUSION CRITERIA: 1) Subjects who are able to understand and are willing to comply to trial instructions. 2) Having given written informed consent. 3) Age 18 to 75 years (inclusively). 4) Diagnosis of acute non‐purulent rhinosinusitis with an appearance of sinusitis symptoms = 5 days confirmed by ultrasonography of paranasal sinuses. 5) Baseline investigator‐evaluated major symptom score (MSS) of =8 and =12 (of maximal 15 score points), out of the 5 main rhinosinusitis symptoms at least 3 must be present. Among these the presence of nasal congestion and facial pain / pressure is mandatory. 6) Presence of nasal congestion (score of = 1 on four‐point rating scale). 7) Mild to moderate facial pain/pressure (score of = 1 and = 2 on four‐point rating scale). 8) Satisfactory health condition except for the rhinosinusitis as determined by the investigator based on medical history and physical examination. 9