Clinical trial NCT02746042: Sinupret Extract Coated Tablets in Chronic Rhinosinusitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Rhinosinusitis
Keywords: chronic rhinosinusitis
Sinupret extract
herbal medicinal product
Lead sponsor: Bionorica SE
Sponsor class: INDUSTRY
First posted: 2016-04-21
Enrollment: 572
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: MSS-INV at V7
timeFrame: 16 weeks
Secondary outcomes:
measure: MSS-INV at V4-6
timeFrame: 12 weeks
measure: MSS-PAT at V4-7
timeFrame: 16 weeks
measure: Minimal MSS-INV at V4-7
timeFrame: 16 weeks
measure: Minimal MSS-PAT at V4-7
timeFrame: 16 weeks
measure: Investigator's Ratings of CRS symptom
timeFrame: 16 weeks
measure: Patient's Ratings of CRS symptom
timeFrame: 16 weeks
measure: SNOT-22
timeFrame: 16 weeks
measure: VAS
timeFrame: 16 weeks
measure: Responder Rate
timeFrame: 16 weeks
measure: Concomitant drug and non-drug therapy
timeFrame: 22 weeks
measure: Premature Terminations
timeFrame: 20 weeks
measure: Investigator's and patient's overall assessment of efficacy (questionnaire)
timeFrame: 16 weeks
measure: WPAI:GH questionnaire
timeFrame: 22 weeks
measure: Inflammatory Parameter IL-1beta (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter IL-2 (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter IL-4 (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter IL-6 (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter IL-8 (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter IFN-gamma (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter TNF-alpha (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter MPO (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter ECP (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter alpha-2-macroglobulin (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter HMGB-1 (nasal secretions: substudy)
timeFrame: 16 weeks
measure: Inflammatory Parameter albumin (nasal secretions: substudy)
timeFrame: 16 weeks
Other outcomes:
measure: Safety Endpoints
timeFrame: 22 weeks
Locations:
city: Berlin
country: Germany
facility: Bionorica Investigative Site
city: Braunschweig
country: Germany
facility: Bionorica Investigative Site
city: Chemnitz
country: Germany
facility: Bionorica Investigative Site
city: Dresden
country: Germany
facility: Bionorica Investigative Site
city: Dresden
country: Germany
facility: Bionorica Investigative Site
city: Dresden
country: Germany
facility: Bionorica Investigative Site
city: Dresden
country: Germany
facility: Bionorica Investigative Site
city: Duisburg
country: Germany
facility: Bionorica Investigative Site
city: Essen
country: Germany
facility: Bionorica Investigative Site
city: Frankfurt am Main
country: Germany
facility: Bionorica Investigative Site
city: Goettingen
country: Germany
facility: Bionorica Investigative Site
city: Heidelberg
country: Germany
facility: Bionorica Investigative Site
city: Heidelberg
country: Germany
facility: Bionorica Investigative Site
city: Markkleeberg
country: Germany
facility: Bionorica Investigative Site
city: Mittweida
country: Germany
facility: Bionorica Investigative Site
city: Munich
country: Germany
facility: Bionorica Investigative Site
city: Neuenhagen
country: Germany
facility: Bionorica Investigative Site
city: Nuremberg
country: Germany
facility: Bionorica Investigative Site
city: Röthenbach/Pegnitz
country: Germany
facility: Bionorica Investigative Site
city: Schluchtern
country: Germany
facility: Bionorica Investigative Site
city: Schorndorf
country: Germany
facility: Bionorica Investigative Site
city: Wuppertal
country: Germany
facility: Bionorica Investigative Site
city: Bialystok
country: Poland
facility: Bionorica Investigative Site
city: Bialystok
country: Poland
facility: Bionorica Investigative Site
city: Bydgoszcz
country: Poland
facility: Bionorica Investigative Site
city: Gdansk
country: Poland
facility: Bionorica Investigative Site
city: Gdynia
country: Poland
facility: Bionorica Investigative Site
city: Katowice
country: Poland
facility: Bionorica Investigative Site
city: Katowice
country: Poland
facility: Bionorica Investigative Site
city: Katowice
country: Poland
facility: Bionorica Investigative Site
city: Kielce
country: Poland
facility: Bionorica Investigative Site
city: Krakow
country: Poland
facility: Bionorica Investigative Site
city: Krakow
country: Poland
facility: Bionorica Investigative Site
city: Krakow
country: Poland
facility: Bionorica Investigative Site
city: Limanowa
country: Poland
facility: Bionorica Investigative Site
city: Lodz
country: Poland
facility: Bionorica Investigative Site
city: Lublin
country: Poland
facility: Bionorica Investigative Site
city: Piaseczno
country: Poland
facility: Bionorica Investigative Site
city: Szczecin
country: Poland
facility: Bionorica Investigative Site
city: Tychy
country: Poland
facility: Bionorica Investigative Site
city: Warszawa
country: Poland
facility: Bionorica Investigative Site
city: Wieliczka
country: Poland
facility: Bionorica Investigative Site
city: Wroclaw
country: Poland
facility: Bionorica Investigative Site
city: Zgierz
country: Poland
facility: Bionorica Investigative Site 222
city: Zgierz
country: Poland
facility: Bionorica Investigative Site 224
Study officials:
affiliation: Praxis Dr. Jürgen Palm, 90552 Röthenbach/Pegnitz, Germany
name: Jürgen Palm, Dr.
role: PRINCIPAL_INVESTIGATOR
References: