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Sinupret Extract Coated Tablets in Chronic Rhinosinusitis

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ClinicalTrials.gov Identifier: NCT02746042
Recruitment Status : Completed
First Posted : April 21, 2016
Last Update Posted : February 28, 2018
Sponsor:
Information provided by (Responsible Party):
Bionorica SE

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

Condition or disease Intervention/treatment Phase
Chronic Rhinosinusitis Drug: Sinupret extract coated tablets Drug: Placebo coated tablets Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 572 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 28, 2016
Actual Primary Completion Date : July 26, 2017
Actual Study Completion Date : August 23, 2017

Arm Intervention/treatment
Experimental: Sinupret extract coated tablets

Sinupret extract coated tablets: one tablet three times a day orally during the 16-week treatment phase.

There will be no dose change during the trial.

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

Placebo Comparator: Placebo coated tablets
Placebo coated tablets: One tablet three times a day orally during the 16-week treatment Phase.
Drug: Placebo coated tablets
1 coated tablet 3 times a day for 16-weeks (1-1-1)
Other Name: Placebo




Primary Outcome Measures :
  1. MSS-INV at V7 [ Time Frame: 16 weeks ]
    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


Secondary Outcome Measures :
  1. MSS-INV at V4-6 [ Time Frame: 12 weeks ]
    Major Symptom Score (MSS) assessed by the investigator at Visits 4, 5, and 6 with Baseline as Covariate

  2. MSS-PAT at V4-7 [ Time Frame: 16 weeks ]
    Major Symptom Score (MSS) assessed by the Patient at Visits 4, 5, 6, and 7 with Baseline as Covariate

  3. Minimal MSS-INV at V4-7 [ Time Frame: 16 weeks ]
    Minimal Major Symptom Score (MSS) assessed by the Investigator of all visits from Visits 4, 5, 6, and 7

  4. Minimal MSS-PAT at V4-7 [ Time Frame: 16 weeks ]
    Minimal Major Symptom Score (MSS) assessed by the Patient of all visits from Visits 4, 5, 6, and 7

  5. Investigator's Ratings of CRS symptom [ Time Frame: 16 weeks ]
    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 CRS symptom [ Time Frame: 16 weeks ]
    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. SNOT-22 [ Time Frame: 16 weeks ]
    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

  8. VAS [ Time Frame: 16 weeks ]
    Total symptom severity assessed by the patient on a visual analogue scale (VAS) at V4, V5, V6, and V7

  9. Responder Rate [ Time Frame: 16 weeks ]
    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%

  10. Concomitant drug and non-drug therapy [ Time Frame: 22 weeks ]
    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. Premature Terminations [ Time Frame: 20 weeks ]
    Number of patients with premature termination due to exacerbation of CRS symptoms

  12. Investigator's and patient's overall assessment of efficacy (questionnaire) [ Time Frame: 16 weeks ]
    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).

  13. WPAI:GH questionnaire [ Time Frame: 22 weeks ]
    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

  14. Inflammatory Parameter IL-1beta (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    Absolute concentrations and total amount per sample of interleukin-1β (IL-1beta) in nasal secretions collected at V2, V5, and V7 for a subset of approximately 60 patients in selected investigational sites in Germany

  15. Inflammatory Parameter IL-2 (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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. Inflammatory Parameter IL-4 (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  17. Inflammatory Parameter IL-6 (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  18. Inflammatory Parameter IL-8 (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  19. Inflammatory Parameter IFN-gamma (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  20. Inflammatory Parameter TNF-alpha (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  21. Inflammatory Parameter MPO (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  22. Inflammatory Parameter ECP (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  23. Inflammatory Parameter alpha-2-macroglobulin (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    Absolute concentrations and total amount per sample of α2-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

  24. Inflammatory Parameter HMGB-1 (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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

  25. Inflammatory Parameter albumin (nasal secretions: substudy) [ Time Frame: 16 weeks ]
    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


Other Outcome Measures:
  1. Safety Endpoints [ Time Frame: 22 weeks ]

    The safety endpoints include:

    1. AEs, SAEs, and treatment-emergent adverse events (TEAEs).
    2. Incidence of adverse drug reactions (ADRs).
    3. Investigator's and patient's overall assessment of tolerability at V7.
    4. Change from baseline (V2) in vital signs after 16 weeks of treatment (V7).
    5. Individual changes from baseline (V2) in safety laboratory parameters after 16 weeks of treatment (V7).
    6. Change from screening (V1) in physical examination (including weight) after 16 weeks of treatment (V7).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02746042


Locations
Germany
Bionorica Investigative Site
Berlin, Germany, 13353
Bionorica Investigative Site
Braunschweig, Germany
Bionorica Investigative Site
Chemnitz, Germany
Bionorica Investigative Site
Dresden, Germany, 01067
Bionorica Investigative Site
Dresden, Germany, 01139
Bionorica Investigative Site
Dresden, Germany, 01159
Bionorica Investigative Site
Dresden, Germany, 01307
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, 69120
Bionorica Investigative Site
Heidelberg, Germany, 69126
Bionorica Investigative Site
Markkleeberg, Germany
Bionorica Investigative Site
Mittweida, Germany
Bionorica Investigative Site
Munich, Germany, 80331
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, Germany
Poland
Bionorica Investigative Site
Bialystok, Poland, 15-270
Bionorica Investigative Site
Bialystok, Poland, 15-879
Bionorica Investigative Site
Bydgoszcz, Poland
Bionorica Investigative Site
Gdansk, Poland
Bionorica Investigative Site
Gdynia, Poland
Bionorica Investigative Site
Katowice, Poland, 40-036
Bionorica Investigative Site
Katowice, Poland, 40-611
Bionorica Investigative Site
Katowice, Poland, 40-954
Bionorica Investigative Site
Kielce, Poland
Bionorica Investigative Site
Krakow, Poland, 30-349
Bionorica Investigative Site
Krakow, Poland, 30-548
Bionorica Investigative Site
Krakow, Poland, 31-624
Bionorica Investigative Site
Limanowa, Poland
Bionorica Investigative Site
Lodz, Poland
Bionorica Investigative Site
Lublin, Poland, 20-552
Bionorica Investigative Site
Piaseczno, Poland
Bionorica Investigative Site
Szczecin, Poland
Bionorica Investigative Site
Tychy, Poland
Bionorica Investigative Site
Warszawa, Poland, 01-868
Bionorica Investigative Site
Wieliczka, Poland
Bionorica Investigative Site
Wroclaw, Poland
Bionorica Investigative Site 222
Zgierz, Poland
Bionorica Investigative Site 224
Zgierz, Poland
Sponsors and Collaborators
Bionorica SE
Investigators
Principal Investigator: Jürgen Palm, Dr. Praxis Dr. Jürgen Palm, 90552 Röthenbach/Pegnitz, Germany

Responsible Party: Bionorica SE
ClinicalTrials.gov Identifier: NCT02746042     History of Changes
Other Study ID Numbers: CRS-03
2015-001952-31 ( EudraCT Number )
First Posted: April 21, 2016    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: It is currently not planned to annex individual participant data (IPD) to publications of the study results.

Keywords provided by Bionorica SE:
chronic rhinosinusitis
Sinupret extract
herbal medicinal product

Additional relevant MeSH terms:
Sinusitis
Paranasal Sinus Diseases
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases