Rhinosinusitis
Conditions
Keywords
CRS, without polyposis
Brief summary
The study should create data for the selection of a clinically relevant endpoint to assess the potential of Buparid/PARI SINUS to postpone sinus surgery in patients with chronic Rhinosinusitis.
Detailed description
The objective of this study is to analyse whether Buparid/PARI SINUS has a higher potential to avoid or postpone sinus surgery in adult patients with CRS than Standard of Care therapy with Budes® Nasal Spray. The results of this study are expected to provide estimates for a proper sample size calculation to conduct a pivotal study.
Interventions
DRUGBudesonide
Inhalation
Sponsors
Pari Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with confirmed diagnosis of chronic rhinosinusitis * Patient without alternative other than sinus surgery * Patient's written informed consent obtained prior to any screening or study-specific procedure * Male or female, ≥ 18 years of age * Patient is able to undergo nasal therapy without restrictions * Capable to correctly use the PARI SINUS device * Capable of understanding the purpose and risk of the clinical trial * Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration. * Patient is able to participate in the study according to Investigator's opinion
Exclusion criteria
* Patients with cystic fibrosis * Patients with polyposis nasi grade I-IV * Patients with prior FESS (Functional Endoscopic Sinus Surgery) * Pregnant or breastfeeding women * Any active invasive bacterial, viral or fungal infection within one week prior to first investigational medicinal product (IMP) administration * No clinically relevant abnormal parameters of vital signs, blood biochemistry or renal/hepatic function * Unlikely to comply with visits, inhalation procedures or other measurements scheduled in the protocol * Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to first administration of IMP * Any co-existing medical condition that in the Investigator's judgement will substantially increase the risk associated with the patient's participation in the clinical trial * Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures * Drug or alcohol abuse * End-stage malignancies * Known hypersensitivity to Budesonide * Patients with oral steroid therapy within the last 3 months * Patients needing \> 1 mg/day Budesonide (or steroidal equivalent) for therapy of asthma * Patients on therapy with leukotriene-receptor antagonists, decongestants, antihistamines or antibiotics * Patients with frequent epistaxis (\> 1 episode per week)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Inflammation of the Nasal Mucosa and Paranasal Sinus | Change from Baseline to week 8 | Inflammation of the nasal mucosa and paranasal sinus was assessed using the Lund-Mackay score based on magnetic resonance imaging. The score can take on values between 0 and 24 points, with higher values indicating more severe thickness of the mucosa or opacification. The outcome investigated is the intraindividual mean score of 2 independent raters assessing the same images. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health-specific Quality of Life | change of SNOT-20 total score from baseline to week 48 | Health-specific quality of life was assessed by means of the self-rated, 20-item Sino-Nasal Outcome Test (SNOT-20). The SNOT-20 total score has a (theoretical) range of 0 - 100 points, with higher scores indicating more severe impairment. Presented are the mean values of the SNOT-20 total score after 48 weeks minus value at day 0 (baseline). |
| Nasal Obstruction | 4 weeks / 8 weeks | Nasal obstruction was assessed using the method of rhinomanometry by measuring the positive nasal inspiratory flow (PNIF). For the assessment the subject had to inhale maximally through the nose three times and the highest value of flow rate was recorded after 4 weeks and 8 weeks of treatment. |
| Inflammation of the Nasal Mucosa and Paranasal Sinus | Changes from Baseline at Week 8 | Determination of the thickness of the mucosa using Magnetic Resonance Imaging |
| Safety Assessment | 48 weeks | Treatment-emergent adverse events |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buparid; Treatment A Buparid 1mg budesonide/2 ml nebulizer solution
Budesonide: Inhalation Solution | 10 |
| Budes; Treatment B Budes Nasal Spray 50 µg budesonide/pump
Budesonide: Nasal Spray | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Budes; Treatment B | Total | Buparid; Treatment A |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 19 Participants | 10 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Germany | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 |
| other Total, other adverse events | 5 / 10 | 6 / 9 |
| serious Total, serious adverse events | 1 / 10 | 0 / 9 |
Outcome results
Primary
Change of Inflammation of the Nasal Mucosa and Paranasal Sinus
Inflammation of the nasal mucosa and paranasal sinus was assessed using the Lund-Mackay score based on magnetic resonance imaging. The score can take on values between 0 and 24 points, with higher values indicating more severe thickness of the mucosa or opacification. The outcome investigated is the intraindividual mean score of 2 independent raters assessing the same images.
Time frame: Change from Baseline to week 8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparid; Treatment A | Change of Inflammation of the Nasal Mucosa and Paranasal Sinus | 0 score on a scale |
| Budes; Treatment B | Change of Inflammation of the Nasal Mucosa and Paranasal Sinus | -0.8 score on a scale |
Secondary
Health-specific Quality of Life
Health-specific quality of life was assessed by means of the self-rated, 20-item Sino-Nasal Outcome Test (SNOT-20). The SNOT-20 total score has a (theoretical) range of 0 - 100 points, with higher scores indicating more severe impairment. Presented are the mean values of the SNOT-20 total score after 48 weeks minus value at day 0 (baseline).
Time frame: change of SNOT-20 total score from baseline to week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Buparid; Treatment A | Health-specific Quality of Life | 17.1 score on a scale |
| Budes; Treatment B | Health-specific Quality of Life | 22.9 score on a scale |
Secondary
Inflammation of the Nasal Mucosa and Paranasal Sinus
Determination of the thickness of the mucosa using Magnetic Resonance Imaging
Time frame: Changes from Baseline at Week 8
Secondary
Nasal Obstruction
Nasal obstruction was assessed using the method of rhinomanometry by measuring the positive nasal inspiratory flow (PNIF). For the assessment the subject had to inhale maximally through the nose three times and the highest value of flow rate was recorded after 4 weeks and 8 weeks of treatment.
Time frame: 4 weeks / 8 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Buparid; Treatment A | Nasal Obstruction | Mean flow rate after 4 weeks | 542.4 ml/sec |
| Buparid; Treatment A | Nasal Obstruction | Mean flow rate after 8 weeks | 461.5 ml/sec |
| Budes; Treatment B | Nasal Obstruction | Mean flow rate after 4 weeks | 582.0 ml/sec |
| Budes; Treatment B | Nasal Obstruction | Mean flow rate after 8 weeks | 551.5 ml/sec |
Secondary
Safety Assessment
Treatment-emergent adverse events
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Buparid; Treatment A | Safety Assessment | 6 Participants |
| Budes; Treatment B | Safety Assessment | 6 Participants |