Sinupret Extract Coated Tablets in Chronic Rhinosinusitis

Chronic Rhinosinusitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02746042
• Other study ID #: CRS-03
• Secondary ID: 2015-001952-31
• Status: Completed
• Phase: Phase 3
• First received: April 18, 2016
• Last updated: February 27, 2018
• Start date: April 28, 2016
• Est. completion date: August 23, 2017

Study information

• Verified date: December 2017
• Source: Bionorica SE
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 572
• Est. completion date: August 23, 2017
• Est. primary completion date: July 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 (a-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

Related Conditions & MeSH terms

• Chronic Rhinosinusitis
• Sinusitis

Intervention

Drug:
• Sinupret extract coated tablets
1 coated tablet 3 times a day for 16-weeks (1-1-1)
• Placebo coated tablets
1 coated tablet 3 times a day for 16-weeks (1-1-1)

Locations

Country	Name	City	State
Germany	Bionorica Investigative Site	Berlin
Germany	Bionorica Investigative Site	Braunschweig
Germany	Bionorica Investigative Site	Chemnitz
Germany	Bionorica Investigative Site	Dresden
Germany	Bionorica Investigative Site	Dresden
Germany	Bionorica Investigative Site	Dresden
Germany	Bionorica Investigative Site	Dresden
Germany	Bionorica Investigative Site	Duisburg
Germany	Bionorica Investigative Site	Essen
Germany	Bionorica Investigative Site	Frankfurt am Main
Germany	Bionorica Investigative Site	Goettingen
Germany	Bionorica Investigative Site	Heidelberg
Germany	Bionorica Investigative Site	Heidelberg
Germany	Bionorica Investigative Site	Markkleeberg
Germany	Bionorica Investigative Site	Mittweida
Germany	Bionorica Investigative Site	Munich
Germany	Bionorica Investigative Site	Neuenhagen
Germany	Bionorica Investigative Site	Nuremberg
Germany	Bionorica Investigative Site	Röthenbach/Pegnitz
Germany	Bionorica Investigative Site	Schluchtern
Germany	Bionorica Investigative Site	Schorndorf
Germany	Bionorica Investigative Site	Wuppertal
Poland	Bionorica Investigative Site	Bialystok
Poland	Bionorica Investigative Site	Bialystok
Poland	Bionorica Investigative Site	Bydgoszcz
Poland	Bionorica Investigative Site	Gdansk
Poland	Bionorica Investigative Site	Gdynia
Poland	Bionorica Investigative Site	Katowice
Poland	Bionorica Investigative Site	Katowice
Poland	Bionorica Investigative Site	Katowice
Poland	Bionorica Investigative Site	Kielce
Poland	Bionorica Investigative Site	Krakow
Poland	Bionorica Investigative Site	Krakow
Poland	Bionorica Investigative Site	Krakow
Poland	Bionorica Investigative Site	Limanowa
Poland	Bionorica Investigative Site	Lodz
Poland	Bionorica Investigative Site	Lublin
Poland	Bionorica Investigative Site	Piaseczno
Poland	Bionorica Investigative Site	Szczecin
Poland	Bionorica Investigative Site	Tychy
Poland	Bionorica Investigative Site	Warszawa
Poland	Bionorica Investigative Site	Wieliczka
Poland	Bionorica Investigative Site	Wroclaw
Poland	Bionorica Investigative Site 222	Zgierz
Poland	Bionorica Investigative Site 224	Zgierz

Sponsors (1)

Lead Sponsor	Collaborator
Bionorica SE

Countries where clinical trial is conducted

Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety Endpoints	The safety endpoints include: AEs, SAEs, and treatment-emergent adverse events (TEAEs).; Incidence of adverse drug reactions (ADRs).; Investigator's and patient's overall assessment of tolerability at V7.; Change from baseline (V2) in vital signs after 16 weeks of treatment (V7).; Individual changes from baseline (V2) in safety laboratory parameters after 16 weeks of treatment (V7).; Change from screening (V1) in physical examination (including weight) after 16 weeks of treatment (V7).	22 weeks
Primary	MSS-INV at V7	Major Symptom Score (MSS) assessed by the investigator at Visit 7 with Baseline as Covariate; The MSS considers: rhinorrhea [anterior], rhinorrhea [posterior], nasal congestion, headache, and facial pain/pressure	16 weeks
Secondary	MSS-INV at V4-6	Major Symptom Score (MSS) assessed by the investigator at Visits 4, 5, and 6 with Baseline as Covariate	12 weeks
Secondary	MSS-PAT at V4-7	Major Symptom Score (MSS) assessed by the Patient at Visits 4, 5, 6, and 7 with Baseline as Covariate	16 weeks
Secondary	Minimal MSS-INV at V4-7	Minimal Major Symptom Score (MSS) assessed by the Investigator of all visits from Visits 4, 5, 6, and 7	16 weeks
Secondary	Minimal MSS-PAT at V4-7	Minimal Major Symptom Score (MSS) assessed by the Patient of all visits from Visits 4, 5, 6, and 7	16 weeks
Secondary	Investigator's Ratings of CRS symptom	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	16 weeks
Secondary	Patient's Ratings of CRS symptom	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	16 weeks
Secondary	SNOT-22	22-Item Sino-Nasal Outcome Test (SNOT-22)Total Score as well as SNOT-22 primary nasal score (SNOT-22 PNS) and SNOT-22 general quality of life score (SNOT-22 ALQ) at V4, V5, V6, and V7	16 weeks
Secondary	VAS	Total symptom severity assessed by the patient on a visual analogue scale (VAS) at V4, V5, V6, and V7	16 weeks
Secondary	Responder Rate	Proportion of patients whose MSS-INV and MSS-PAT 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%	16 weeks
Secondary	Concomitant drug and non-drug therapy	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	22 weeks
Secondary	Premature Terminations	Number of patients with premature termination due to exacerbation of CRS symptoms	20 weeks
Secondary	Investigator's and patient's overall assessment of efficacy (questionnaire)	At each on-site visit during the treatment phase (V4 to V7), both the investigator and the patient have to provide an overall assessment of treatment efficacy using 5 categories ("very good", "good", "moderate", "poor", and "very poor"; ranges from 0 to 4).	16 weeks
Secondary	WPAI:GH questionnaire	Pharmacoeconomic evaluation (utilization of health care resources) based on "Work Productivity and Activity Impairment, Global Health" (WPAI:GH) questionnaire completed by the patient at V4, V5, V6, and V7	22 weeks
Secondary	Inflammatory Parameter IL-1beta (nasal secretions: substudy)	Absolute concentrations and total amount per sample of interleukin-1ß (IL-1beta) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter IL-2 (nasal secretions: substudy)	Absolute concentrations and total amount per sample of interleukin-2 (IL-2) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter IL-4 (nasal secretions: substudy)	Absolute concentrations and total amount per sample of interleukin-4 (IL-4) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter IL-6 (nasal secretions: substudy)	Absolute concentrations and total amount per sample of interleukin-6 (IL-6) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter IL-8 (nasal secretions: substudy)	Absolute concentrations and total amount per sample of interleukin-8 (IL-8) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter IFN-gamma (nasal secretions: substudy)	Absolute concentrations and total amount per sample of interferon gamma (IFN-gamma) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter TNF-alpha (nasal secretions: substudy)	Absolute concentrations and total amount per sample of tumor necrosis factor alpha (TNF-alpha) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter MPO (nasal secretions: substudy)	Absolute concentrations and total amount per sample of myeloperoxidase (MPO) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter ECP (nasal secretions: substudy)	Absolute concentrations and total amount per sample of eosinophil cationic protein (ECP) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter alpha-2-macroglobulin (nasal secretions: substudy)	Absolute concentrations and total amount per sample of a2-macroglobulin (alpha-2-macroglobulin) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter HMGB-1 (nasal secretions: substudy)	Absolute concentrations and total amount per sample of high-mobility group box protein 1 (HMGB-1) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks
Secondary	Inflammatory Parameter albumin (nasal secretions: substudy)	Absolute concentrations and total amount per sample of albumin in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany	16 weeks