A Multicentre, Randomised, Double-blind, Placebo-controlled, Parallel Group Trial to Assess Efficacy and Safety of Two Dosages of a Herbal Medicinal Product (Dry Extract BNO 1016) in Patients With Chronic Rhinosinusitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bionorica SE
- 入组人数
- 927
- 试验地点
- 1
- 主要终点
- Average of investigator's Major Symptom Score ratings [score points] at V5 and V6
研究概览
简要总结
The purpose of this trial is to determine whether 2 different dosages of a herbal extract (240 and 480 mg/day) are more effective than placebo in the treatment of patients with chronic rhinosinusitis (average reduction of investigator's Major Symptom Score over Visit 5 and Visit 6.
详细描述
The clinical trial population consists of patients presenting with two or more typical symptoms of CRS and duration of symptoms of at least ≥12 weeks. The diagnosis should have been confirmed with the initial diagnosis of CRS by nasal endoscopy and/or computer tomography (CT) and by obligatory nasal endoscopy including exclusion of nasal polyps during screening phase.
A total of 885 patients will be included in this clinical trial, which will last for approximately 12 months, including screening, treatment and medication-free follow-up period as well as final reporting. The duration for the individual patient is approximately 22 weeks (Visit 1 - Visit 7). After a 2-week screening phase, treatment will be started by application of either 240 mg or 480 mg daily dose (t.i.d.) or placebo for 12 weeks followed by a medication-free follow-up period.
Symptoms often do not correlate to the findings in nasal endoscopy or CT. Therefore, efficacy in this clinical trial is defined as per clinical definition using five individual rhinosinusitis symptoms (MSS)graded by the investigator using increasing severity grading(0 = absent [none / not present], 1 = mild, 2 = moderate, 3 = severe).
Secondary outcome measures include
- single rhinosinusitis symptoms of CRS (MSSINV and MSSPAT),
- Work Productivity and Activity Impairment patient questionnaire related to General Health [WPAI:GH],
- total symptom severity by Visual Analogue Scale
- response to treatment rated by investigator and patient
- 20-Question Sino-Nasal Outcome Test [SNOT-20, only Germany]
- percentage of patients with permitted concomitant medication for the treatment of CRS
- premature termination due to exacerbations of symptoms
- post treatment course of CRS will
- pharmacoeconomic assessments
- safety and tolerability of trial treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent including data protection declaration
- •Male and female outpatients aged ≥18 and ≤75 years
- •Diagnosis of bilateral chronic rhinosinusitis without nasal polyps confirmed by:
- •nasal endoscopy during the screening period (nasal endoscopy results not older than 2 month will be accepted) to confirm inflammation, mucopurulent discharge and/or oedema/mucosal obstruction primarily in middle meatus without nasal polyps being present
- •at the discretion of the investigator a historic CT (before screening and not older than 24 months) 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)
- •Bilateral chronic rhinosinusitis characterized by (V1 and V2):
- •presence of chronic rhinosinusitis symptoms for at least 12 weeks without complete resolution of symptoms prior to enrolment (V1)
- •a MSS ≥6 points and ≤12 points for each of the screening days observed by diary entries (MSSPAT)and on the days of Visit 1 and 2 (MSSINV)
- •on 5 random days of the screening period (or at least at days -5 to -1) assessed by MSSPAT and on the day of Visit 1 and 2 assessed by MSSINV: rhinorrhoea (anterior or posterior) and pain (facial pain or headache) of at least moderate intensity (score ≥2).
排除标准
- •Sinus surgery within the last 2 years (solitary sinus puncture is allowed)
- •Nasal concha surgery within the last 3 months
- •Presence or history of uni- or bilateral nasal polyps
- •Presence of moderate to severe co-morbid asthma, including allergic asthma
- •Patients with mild asthma having exacerbations within 30 days prior to trial inclusion
- •Patients with cystic fibrosis
- •Patients with a positive skin prick test at V1 against allergens to which the patient might be exposed to during the expected individual trial duration, if clinically relevant (results not older than 12 months will be accepted)
- •Clinically relevant perennial (e.g. patients with actual clinical symptoms of allergic rhinitis against house dust/-mite antigen) or actual seasonal allergic rhinitis
- •Rhinitis medicamentosa (drug induced rhinitis)
- •Aspirin-Exacerbated Respiratory Disease [AERD] (Aspirin sensitivity)
- •Dentogenic sinusitis or otherwise unilateral sinusitis
- •Presence of anatomical deviations of the nasal septum that significantly impair nasal and paranasal ventilation / airflow
- •Known hypersensitivity to trial medication or excipients
- •Patients with rare hereditary problems of fructose intolerance, galactose intolerance, lactase deficiency or glucose-galactose malabsorption or sucrase-isomaltase insufficiency
- •Signs or symptoms of acute bacterial sinusitis (e.g. fever > 38.5°C, orbital complications,severe unilateral frontal headache or toothache)
- •Treatment with systemic or nasal antibiotics or corticosteroids within the last 4 weeks prior to V1
- •Treatment with decongestant preparations (α-sympathomimetics), analgesics (including systemic Non-Steroidal Inflammatory Drugs [NSAIDs], except paracetamol), mucolytics / secretolytics, antihistamines, or alternative medicine preparations for treatment of common cold like symptoms or with immunomodulating properties within the last 7 days prior to V1
- •Patients with gastric or duodenal ulcer
- •Other diseases within 5 years prior to V1, which 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 or alcohol or drug abuse or immunodeficiency).
研究组 & 干预措施
80 mg BNO 1016 und placebo
2 tablets (one containing 80 mg BNO 1016 and one placebo) by mouth 3 times daily
干预措施: BNO 1016 (Drug)
160 mg BNO 1016
2 tablets (each containing 80 mg BNO 1016) by mouth 3 times daily
干预措施: BNO 1016 (Drug)
placebo
2 tablets (each without BNO 1016) by mouth 3 times daily
干预措施: BNO 1016 (Drug)
结局指标
主要结局
Average of investigator's Major Symptom Score ratings [score points] at V5 and V6
时间窗: 4 weeks
The primary efficacy endpoint is defined as the average of investigator's Major Symptom Score ratings \[score points\] at V5 and V6 (arithmetic mean of 2 ratings).
次要结局
- Investigator´s MSS ratings [score points] at V4(Day 29)
- Investigtor´s MSS ratings [score points] at V6(Day 85)
- Patient´s MSS ratings [score points] from V5 to V6(4 weeks)
- Investigtor´s MSS ratings [score points] at V7(Day 141)
- Responders based on investigators´ ratings at V2, V3, V4, V5, V6 and V7(20 weeks)
- Investigtor´s MSS ratings [score points] at V3(Day 8)
- Responders based on patients´ ratings at V2, V3, V4, V5, V6 and V7(20 weeks)
- Investigtor´s MSS ratings [score points] at V5(Day 57)