Chronic Rhinosinusitis
Conditions
Brief summary
This is a 24-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of intranasal administration of 186 and 372 μg twice daily (BID) of OPN-375 in subjects with chronic rhinosinusitis (CS) with or without nasal polyps.
Detailed description
The primary objective of this study is to compare the efficacy of intranasal administration of twice-daily doses of 186 and 372 µg of OPN-375 (fluticasone propionate) with placebo in subjects with chronic rhinosinusitis using the following co-primary endpoints: 1. A change from baseline in symptoms as measured by a composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4. 2. A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses.
Interventions
DRUGOPN-375
OPN-375, BID
Sponsors
Optinose US Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Potential subjects must meet the following criteria to enter this study: 1. men or women aged 18 years and older at baseline visit 2. women of childbearing potential must be abstinent, or if sexually active, 1. be practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method \[eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel\], or male partner sterilization) before entry and throughout the study, or 2. be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or 3. be postmenopausal (amenorrhea for at least 1 year) 3. women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening) 4. must have a history of chronic rhinosinusitis (CRS) and be currently experiencing 2 or more of the following symptoms, 1 of which has to be either nasal congestion or nasal discharge (anterior and/or posterior nasal discharge) for equal to or greater than 12 weeks: * nasal congestion * nasal discharge (anterior and/or posterior nasal discharge) * facial pain or pressure * reduction or loss of smell 5. endoscopic evidence of nasal mucosal disease, with edema, purulent discharge, or polyps in middle meatus, bilaterally, or presence of bilateral disease on a prior computed tomography (CT) scan performed within 14 days of Visit 1 6. must have confirmatory evidence via a CT scan of bilateral sinus disease (have at least 1 sinus on each side of nose with a Lund-Mackay score of ≥1) 7. baseline CT scan must show a combined ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus 8. must have at least moderate symptoms (as defined in protocol) of nasal congestion as reported by the subject, on average, for the 7-day period preceding Visit 1 (Screening) run-in 9. must have an average morning score of at least 1.5 for congestion on the Nasal Symptom Scale (as defined in protocol) recorded on the subject diary over a 7-day period during the first 14 days of the single-blind run-in period 10. must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization 11. Subjects with comorbid asthma or chronic obstructive pulmonary disorder (COPD) must be stable with no exacerbations (eg, no emergency room visits, hospitalizations, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Inhaled corticosteroid use must be limited to stable doses of no more than 1,000 μg/day of beclomethasone (or equivalent) for at least 3 months before Visit 1 (Screening) with plans to continue use throughout the study. 12. Subjects with aspirin-exacerbated respiratory disease, who have undergone aspirin desensitization and are receiving daily aspirin therapy, must be receiving therapy for at least 6 months prior to Visit 1. 13. must be able to cease treatment with intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at the screening visit 14. must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening) 15. must be able to use the exhalation delivery system (EDS) correctly; all subjects will be required to demonstrate correct use with the practice EDS at Visit 1 (Screening). 16. must be capable, in the opinion of the investigator, of providing informed consent to participate in the study. Subjects must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Potential subjects who meet any of the following criteria will be excluded from entering this study: 1. women who are pregnant or lactating 2. inability to have each nasal cavity examined for any reason, including nasal septum deviation 3. inability to achieve bilateral nasal airflow 4. is currently taking XHANCE® 5. have previously used XHANCE for more than 1 month and did not achieve an adequate symptomatic response 6. the nasal/sinus anatomy prevents the accurate assessment of sinus volume via CT scan 7. history of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery 8. have current evidence of odontogenic sinusitis, sinus mucocele (the affected sinus is completely opacified and either the margins are expanded and/or thinned OR there are areas of complete bone resorption resulting in bony defect and extension of the mass into adjacent tissues), evidence of allergic fungal sinusitis, or evidence of complicated sinus disease (including, but not limited to, extension of inflammation outside of the sinuses and nasal cavity) 9. have a paranasal sinus or nasal tumor 10. have a polyp extending outside the ostiomeatal complex/middle turbinate (anterior or inferior) that is below the inferior turbinate attachment as determined by the nasoendoscopy at screening 11. have a nasal septum perforation 12. have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening) 13. have evidence of significant mucosal injury, ulceration (eg, exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy 14. have current, ongoing rhinitis medicamentosa (rebound rhinitis) 15. have significant oral structural abnormalities (eg, a cleft palate) 16. have a diagnosis of cystic fibrosis 17. history of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) or dyskinetic ciliary syndromes 18. Symptom resolution or last dose of antibiotics for purulent nasal infection, acute sinusitis, or upper respiratory tract infection, influenza, or SARS-CoV-2 (COVID-19) has not occurred before Visit 1 or was less than 4 weeks before the CT scan. Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution. 19. planned sinonasal surgery during the period of the study 20. allergy, hypersensitivity, or contraindication to corticosteroids or steroids 21. has used oral steroids in the past for treatment of CRS and did not experience any relief of symptoms 22. has a steroid eluting sinus stent still in place within 30 days of Visit 1 23. allergy or hypersensitivity to any excipients in study drug 24. exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral, intra-articular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD 25. have nasal candidiasis 26. history or current diagnosis of any form of glaucoma or ocular hypertension 27. history of intraocular pressure (IOP) elevation on any form of steroid therapy 28. history or current diagnosis of the presence (in either eye) of a cataract unless both natural intraocular lenses have been removed 29. history of immunodeficiency 30. any serious or unstable concurrent disease, psychiatric disorder, or any significant condition that, in the opinion of the investigator could confound the results of the study or could interfere with the subject's participation or compliance in the study 31. have a positive drug screen or a recent (within 1 year of Visit 1 \[Screening\]) history of drug or alcohol abuse, or dependence that, in the opinion of the investigator could interfere with the subject's participation or compliance in the study 32. have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening) 33. have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1 (Screening) 34. is using strong cytochrome P450 3A4 (CYP3A4) inhibitor (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole, cobicistat) 35. is an employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or is a family member of the employee or the investigator 36. Patients who report unexplained worsening of vision within the past 3 months (e.g. difficulty reading or seeing traffic signs from a distance.). A diagnosis of presbyopia established by an eye doctor is not exclusionary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4 | 4 Weeks | Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9. |
| Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses | Baseline, Week 24 | Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent volume opacified can range from 0% to 100%. Outcome measure is the percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery | Baseline, Week 24 | Percentage of subjects indicating that they are willing to consider Sinus Surgery |
| Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ | 24 Weeks | The SIT is a test comprised of 4 booklets each containing 10 microencapsulated (scratch and sniff) odors. Forced choice response alternatives to identify the odor accompany each test item. Each correct response is assigned a score of 1 and incorrect responses are assigned a score of 0. The total score is calculated by summing the scores of each individual odor for a total possible score ranging from 0-40. The higher the score, the better the individual's sense of smell. The test provides an absolute indication of smell loss (anosmia; mild, moderate or severe hyposmia) as well as an index to detect malingering. |
| Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS) | 24 Weeks | The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The outcome measured for this study was the EQ VAS, which records the subject's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflects the subject's own judgement. VAS scores range from 0 (worst health you can imagine) to 100 (best health you can imagine). |
| Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument | 24 Weeks | The SF-6D is a single health state index derived from the 11 items from the SF-36v2. SF-6D scores range from 0 (worst health state) to 1 (best health state). |
| Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention | Baseline, Week 24 | Percentage of Subjects who meet the minimal objective criteria for surgical intervention |
| Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery | Week 24 | Outcome value presented here is the percent of subjects who are approved for surgery but no longer elect to undergo a surgery. The number of participants analyzed indicates the total number of participants for whom this analysis was completed. |
| Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ). | 24 Weeks | The Health and Work Performance Questionnaire measures work productivity (absenteeism and presenteeism). - Absenteeism is measured in missed work days over the past four weeks (range 0-20); absenteeism is measured in % productivity at work (0-100%), with higher values indicating improved productivity. Values for this outcome are reported as the change in relative absenteeism (the percentage of productivity at work) from baseline to Week 24. |
| Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Week 24 | The SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional consequences of their nasal disorder across several domains including: rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem,3=moderate problem, 4=severe problem, 5=problem as bad as it can be. |
| Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) | Week 12 | Change from baseline in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9. |
| Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores | 12 Weeks | Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours), The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living. |
| Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores | 12 Weeks | Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours) The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent. The change reported in the results is calculated by subtracting the score reported at Baseline from the score reported at Visit 4 (Week 12). |
| Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores | 12 Weeks | Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living. |
| Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores | 12 Weeks | Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living. The value reported in the results is calculated by subtracting the score reported by the patient at Baseline from the score reported by the patient at Visit 4 (Week 12). |
| Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | 24 Weeks | Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT for CRS with Nasal Polyps (NP) and without NP sub-groups and in patients with and without previous sinus surgery. Percent volume opacified can range from 0% to 100%. Outcome measure is percentage change from percent opacification at baseline to percent opacification at Week 24; therefor, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%. |
| Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score | Baseline, Week 24 | Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for each of the left and right ostiomeatal complex (OMC). The total LM score for a CT scan ranges from 0-24. |
| Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined | 24 Weeks | Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC). The values reported for this outcome are the change in total opacification of the left and right maxillary and ethmoid sinuses (Visit 6 \[Wk 24\] score minus Baseline score). Each visit score can range from a total of 0-12 (sum of 0-2 score assigned for each of left and right maxillary, left and right anterior ethmoid, and left and right posterior ethmoid). |
| Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Week 24 | Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC). Each sinus pair (left and right side) listed below can achieve a total score of 0-4 (sum of 0-2 for each side). The values reported below are calculated by subtracting the total score at Baseline from the total score at Visit 6 (Wk 24). |
| Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment | Baseline, Week 24 | — |
| Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment | Baseline, Week 24 | — |
| Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | 24 Weeks | Percent of sinus volume occupied by disease in the worst sinus between maxillary and ethmoid sinuses for the total population, chronic rhinosinusitis with nasal polyps (CRSwNP) subgroup, chronic rhinosinusitis without nasal polyps (CRSsNP) subgroup, patients with previous sinus surgery subgroup, and without previous surgery subgroup. |
| Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score | Baseline, Week 24 | Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% for each sinus. Total score ranges from 0 to 50. |
| Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | Baseline, Week 24 | Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% The total score for the combined ethmoids and maxillary sinuses can range from 0-30 (0-5 for each left and right of the anterior ethmoid, posterior ethmoid, and maxillary sinuses). The outcome values presented in the results are determined by subtracting the total score at Baseline from the total score at Week 24. |
| Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Baseline, Week 24 | Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% Each sinus pair (left and right side) listed below can achieve a total score of 0-10 (sum of score on each side). The values reported for this outcome calculated by subtracting the score at Baseline from the score at Visit 6 (Wk 24). |
| Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Baseline, Week 24 | Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% |
| Time Comparison to First Acute Exacerbation of Chronic Sinusitis | 24 Weeks | Comparing the distribution of time to first acute exacerbation of chronic sinusitis, defined as a worsening of symptoms that requires escalation of treatment |
| Percentage of Subjects Requiring Rescue Medication After Week 4 | 8 Weeks | Recording of each dose of approved rescue medication after the Week 4 visit through Week 12 |
| Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | 12 Weeks, 24 Weeks | The PSQI is a validated, self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate 7 component scores (each ranging between 0 and 3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging between 0 and 21. Higher values represent a worse outcome. |
| Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) | Week 4, Week 24 | Global impression of change will be assessed using a subject-completed PGIC scale range: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse |
| Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Week 24 | The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, where higher scores indicate a worse outcome. |
| Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS) | 24 Weeks | Change from baseline to Week 24/ET on the MCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability. |
| Change in the SF-36v2 Physical Composite Score (PCS) | 24 Weeks | Change from baseline to Week 24/ET on the PCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability. |
| Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | 24 Weeks | The SF-36v2 is a multipurpose, 36-item subject-completed validated questionnaire that measures 8 domains of health: physical functioning, role limitations due to physical health (RP), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The SF-36v2 survey with a 4-week recall will be used. It yields scale scores for each of these 8 health domains , each of which is scored from 0 to 100. Higher scores indicate with a better health status, with 100 representing the highest level of functioning possible. |
| Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | 24 Weeks | The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, with higher scores indicating a worse outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Safety Measuring Vital Signs- Pulse | 24 Weeks | Measure pulse in beats per minute (bpm) |
| Evaluation of Safety Measuring Vital Signs- Weight | 24 Weeks | Assessment of safety from physical examination-weight measured in kg or lb |
| Evaluation of Safety - Monitoring Concomitant Medication Usage | 24 Weeks | Assessment for safety from the collection of information for concomitant medications usage |
| Evaluation of Safety-Nasal Examination | 24 Weeks | Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum. |
| Evaluation of Safety Measuring Vital Signs- Blood Pressure | 24 Weeks | Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg) |
| Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | 24 Weeks | Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe |
Countries
Bulgaria, Canada, Georgia, Poland, Russia, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPN-375 186 μg BID OPN-375 186 μg BID x 24 Weeks
OPN-375: OPN-375, BID | 111 |
| OPN-375 372 μg BID OPN-375 372 μg BID x 24 Weeks
OPN-375: OPN-375, BID | 109 |
| Placebo Matching Placebo BID x 24 Weeks
OPN-375: OPN-375, BID | 112 |
| Total | 332 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 3 |
| Overall Study | Lack of Efficacy | 4 | 2 | 9 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Reason not provided | 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | OPN-375 186 μg BID | OPN-375 372 μg BID | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 16 Participants | 23 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 95 Participants | 93 Participants | 89 Participants | 277 Participants |
| Age, Continuous Mean | 48.4 years STANDARD_DEVIATION 13.85 | 49.6 years STANDARD_DEVIATION 13.49 | 49.2 years STANDARD_DEVIATION 15.26 | 49.1 years STANDARD_DEVIATION 14.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 9 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 100 Participants | 104 Participants | 314 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Any Treatment | 100 participants | 100 participants | 104 participants | 304 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Beclomethasone | 2 participants | 7 participants | 9 participants | 18 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Budesonide | 18 participants | 22 participants | 18 participants | 58 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Ciclesonide | 1 participants | 1 participants | 2 participants | 4 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Flunisolide | 0 participants | 0 participants | 1 participants | 1 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Fluticasone and azelastine | 15 participants | 14 participants | 17 participants | 46 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Fluticasone Furoate | 12 participants | 14 participants | 20 participants | 46 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Fluticasone proprionate | 62 participants | 66 participants | 67 participants | 195 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Mometason Furoate | 44 participants | 51 participants | 48 participants | 143 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Other | 6 participants | 3 participants | 4 participants | 13 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within the last 10 years Triamcinolone | 14 participants | 11 participants | 16 participants | 41 participants |
| Other Chronic Sinusitis Treatment History Saline lavage No | 75 Participants | 59 Participants | 73 Participants | 207 Participants |
| Other Chronic Sinusitis Treatment History Saline lavage Yes | 36 Participants | 50 Participants | 39 Participants | 125 Participants |
| Other Chronic Sinusitis Treatment History Systemic antibiotic in last 5 years No | 67 Participants | 61 Participants | 70 Participants | 198 Participants |
| Other Chronic Sinusitis Treatment History Systemic antibiotic in last 5 years Yes | 44 Participants | 48 Participants | 42 Participants | 134 Participants |
| Prior Sinusitis Surgery Any surgery | 58 participants | 53 participants | 58 participants | 169 participants |
| Prior Sinusitis Surgery Balloon sinuplasty | 5 participants | 4 participants | 5 participants | 14 participants |
| Prior Sinusitis Surgery Endoscopic sinus surgery | 52 participants | 47 participants | 48 participants | 147 participants |
| Prior Sinusitis Surgery Other surgery | 5 participants | 2 participants | 3 participants | 10 participants |
| Prior Sinusitis Surgery Polypectomy alone | 14 participants | 12 participants | 21 participants | 47 participants |
| Prior Sinusitis Surgery Propel mometasone furoate implant | 2 participants | 2 participants | 8 participants | 12 participants |
| Prior Sinusitis Surgery Sinus stent | 2 participants | 2 participants | 8 participants | 12 participants |
| Prior Sinusitis Surgery Sinuva mometasone furoate sinus implant : Yes | 1 participants | 0 participants | 0 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 4 Participants | 6 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 99 Participants | 99 Participants | 101 Participants | 299 Participants |
| Region of Enrollment Bulgaria | 2 participants | 3 participants | 2 participants | 7 participants |
| Region of Enrollment Canada | 2 participants | 7 participants | 7 participants | 16 participants |
| Region of Enrollment Georgia | 2 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Poland | 33 participants | 25 participants | 32 participants | 90 participants |
| Region of Enrollment Russia | 8 participants | 5 participants | 11 participants | 24 participants |
| Region of Enrollment Sweden | 2 participants | 4 participants | 2 participants | 8 participants |
| Region of Enrollment United Kingdom | 0 participants | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 62 participants | 64 participants | 57 participants | 183 participants |
| Sex: Female, Male Female | 47 Participants | 43 Participants | 51 Participants | 141 Participants |
| Sex: Female, Male Male | 64 Participants | 66 Participants | 61 Participants | 191 Participants |
| Sinus imaging in last year CT scans 0 | 64 Participants | 59 Participants | 54 Participants | 177 Participants |
| Sinus imaging in last year CT scans 1 | 40 Participants | 42 Participants | 50 Participants | 132 Participants |
| Sinus imaging in last year CT scans 2 | 6 Participants | 8 Participants | 8 Participants | 22 Participants |
| Sinus imaging in last year CT scans 3 | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sinus imaging in last year MRI scans 0 | 107 Participants | 106 Participants | 105 Participants | 318 Participants |
| Sinus imaging in last year MRI scans 1 | 4 Participants | 3 Participants | 7 Participants | 14 Participants |
| Sinus imaging in last year MRI scans 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sinus imaging in last year MRI scans 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking History Current cigarette smoker | 5 participants | 3 participants | 6 participants | 14 participants |
| Smoking History Current smoker (other forms of tobacco) | 0 participants | 1 participants | 2 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 111 | 0 / 109 | 0 / 112 |
| other Total, other adverse events | 37 / 111 | 37 / 109 | 14 / 112 |
| serious Total, serious adverse events | 1 / 111 | 2 / 109 | 3 / 112 |
Outcome results
Primary
Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4
Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.
Time frame: 4 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4 | -1.58 score on a scale | Standard Error 0.161 |
| OPN-375 372 μg BID | Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4 | -1.60 score on a scale | Standard Error 0.163 |
| Placebo | Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4 | -0.62 score on a scale | Standard Error 0.161 |
Primary
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses
Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent volume opacified can range from 0% to 100%. Outcome measure is the percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses | -5.58 Percentage of volume opacified | Standard Error 1.436 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses | -6.20 Percentage of volume opacified | Standard Error 1.412 |
| Placebo | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses | -1.60 Percentage of volume opacified | Standard Error 1.421 |
Secondary
Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores
Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours), The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.
Time frame: 12 Weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.71 score on a scale | Standard Error 0.074 |
| OPN-375 186 μg BID | Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.68 score on a scale | Standard Error 0.075 |
| OPN-375 372 μg BID | Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.84 score on a scale | Standard Error 0.076 |
| OPN-375 372 μg BID | Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.82 score on a scale | Standard Error 0.076 |
| Placebo | Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.45 score on a scale | Standard Error 0.076 |
| Placebo | Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.41 score on a scale | Standard Error 0.076 |
Secondary
Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores
Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.
Time frame: 12 Weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.65 score on a scale | Standard Error 0.075 |
| OPN-375 186 μg BID | Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.58 score on a scale | Standard Error 0.077 |
| OPN-375 372 μg BID | Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.74 score on a scale | Standard Error 0.076 |
| OPN-375 372 μg BID | Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.72 score on a scale | Standard Error 0.078 |
| Placebo | Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.43 score on a scale | Standard Error 0.077 |
| Placebo | Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.37 score on a scale | Standard Error 0.078 |
Secondary
Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior)
Change from baseline in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.
Time frame: Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) | -1.89 score on a scale | Standard Error 0.204 |
| OPN-375 372 μg BID | Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) | -2.18 score on a scale | Standard Error 0.208 |
| Placebo | Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) | -1.35 score on a scale | Standard Error 0.208 |
Secondary
Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains
The SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional consequences of their nasal disorder across several domains including: rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem,3=moderate problem, 4=severe problem, 5=problem as bad as it can be.
Time frame: Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | -18.05 score on a scale | Standard Error 1.687 |
| OPN-375 372 μg BID | Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | -22.77 score on a scale | Standard Error 1.709 |
| Placebo | Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | -10.16 score on a scale | Standard Error 1.723 |
Secondary
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations
Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT for CRS with Nasal Polyps (NP) and without NP sub-groups and in patients with and without previous sinus surgery. Percent volume opacified can range from 0% to 100%. Outcome measure is percentage change from percent opacification at baseline to percent opacification at Week 24; therefor, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Nasal Polyps Present | -6.01 percentage of volume opacified | Standard Error 1.741 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Nasal Polyps Absent | -3.52 percentage of volume opacified | Standard Error 2.389 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Prior Sinus Surgery | -7.58 percentage of volume opacified | Standard Error 2.156 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | No Prior Sinus Surgery | -3.30 percentage of volume opacified | Standard Error 1.913 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | No Prior Sinus Surgery | -3.82 percentage of volume opacified | Standard Error 1.787 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Nasal Polyps Present | -4.64 percentage of volume opacified | Standard Error 1.744 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Prior Sinus Surgery | -8.91 percentage of volume opacified | Standard Error 2.235 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Nasal Polyps Absent | -7.90 percentage of volume opacified | Standard Error 2.287 |
| Placebo | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | No Prior Sinus Surgery | -0.95 percentage of volume opacified | Standard Error 1.81 |
| Placebo | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Nasal Polyps Absent | -5.50 percentage of volume opacified | Standard Error 2.309 |
| Placebo | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Prior Sinus Surgery | -1.65 percentage of volume opacified | Standard Error 2.185 |
| Placebo | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations | Nasal Polyps Present | 1.29 percentage of volume opacified | Standard Error 1.727 |
Secondary
Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment | -7.31 Percent opacified volume | Standard Error 1.43 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment | -7.43 Percent opacified volume | Standard Error 1.44 |
| Placebo | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment | -3.76 Percent opacified volume | Standard Error 1.44 |
Secondary
Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment | -14.70 Percent opacified volume | Standard Error 2.23 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment | -12.62 Percent opacified volume | Standard Error 2.3 |
| Placebo | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment | -7.61 Percent opacified volume | Standard Error 2.29 |
Secondary
Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations
Percent of sinus volume occupied by disease in the worst sinus between maxillary and ethmoid sinuses for the total population, chronic rhinosinusitis with nasal polyps (CRSwNP) subgroup, chronic rhinosinusitis without nasal polyps (CRSsNP) subgroup, patients with previous sinus surgery subgroup, and without previous surgery subgroup.
Time frame: 24 Weeks
Population: Data is provided for the total population and 4 subgroups. The population of the subgroups will not equal the total population, as they are only a portion of subjects from the total.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Subjects with Prior Sinus Surgery | -11.29 Percent opacified volume | Standard Error 2.67 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | CRSsNP SubGroup | -7.88 Percent opacified volume | Standard Error 2.37 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Full Population | -11.27 Percent opacified volume | Standard Error 1.81 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | CRSwNP SubGroup | -6.54 Percent opacified volume | Standard Error 1.77 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Subjects without Prior Sinus Surgery | -11.00 Percent opacified volume | Standard Error 2.46 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | CRSsNP SubGroup | -7.89 Percent opacified volume | Standard Error 2.37 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Full Population | -10.39 Percent opacified volume | Standard Error 1.83 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | CRSwNP SubGroup | -6.72 Percent opacified volume | Standard Error 1.81 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Subjects with Prior Sinus Surgery | -12.44 Percent opacified volume | Standard Error 2.89 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Subjects without Prior Sinus Surgery | -8.83 Percent opacified volume | Standard Error 2.3 |
| Placebo | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Subjects without Prior Sinus Surgery | -8.39 Percent opacified volume | Standard Error 2.33 |
| Placebo | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Subjects with Prior Sinus Surgery | -3.24 Percent opacified volume | Standard Error 2.85 |
| Placebo | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | Full Population | -6.51 Percent opacified volume | Standard Error 1.82 |
| Placebo | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | CRSsNP SubGroup | -3.88 Percent opacified volume | Standard Error 2.34 |
| Placebo | Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations | CRSwNP SubGroup | -3.23 Percent opacified volume | Standard Error 1.79 |
Secondary
Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score
Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for each of the left and right ostiomeatal complex (OMC). The total LM score for a CT scan ranges from 0-24.
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score | -0.40 score on a scale | Standard Error 0.269 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score | -0.46 score on a scale | Standard Error 0.267 |
| Placebo | Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score | 0.10 score on a scale | Standard Error 0.266 |
Secondary
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined
Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC). The values reported for this outcome are the change in total opacification of the left and right maxillary and ethmoid sinuses (Visit 6 \[Wk 24\] score minus Baseline score). Each visit score can range from a total of 0-12 (sum of 0-2 score assigned for each of left and right maxillary, left and right anterior ethmoid, and left and right posterior ethmoid).
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined | 0.12 score on a scale | Standard Error 0.148 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined | 0.04 score on a scale | Standard Error 0.149 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined | 0.37 score on a scale | Standard Error 0.148 |
Secondary
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs
Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC). Each sinus pair (left and right side) listed below can achieve a total score of 0-4 (sum of 0-2 for each side). The values reported below are calculated by subtracting the total score at Baseline from the total score at Visit 6 (Wk 24).
Time frame: Week 24
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ethmoid Sinus Anterior | 0.06 score on a scale | Standard Error 0.064 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ethmoid Sinus Posterior | 0.00 score on a scale | Standard Error 0.066 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Maxillary Sinus | 0.04 score on a scale | Standard Error 0.049 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Frontal Sinus | 0.08 score on a scale | Standard Error 0.072 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Sphenoid Sinus | 0.04 score on a scale | Standard Error 0.067 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ostiomeatal Complex | -0.66 score on a scale | Standard Error 0.129 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ostiomeatal Complex | -0.47 score on a scale | Standard Error 0.129 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ethmoid Sinus Anterior | -0.01 score on a scale | Standard Error 0.063 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Frontal Sinus | 0.01 score on a scale | Standard Error 0.071 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Sphenoid Sinus | -0.03 score on a scale | Standard Error 0.068 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ethmoid Sinus Posterior | -0.04 score on a scale | Standard Error 0.067 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Maxillary Sinus | 0.09 score on a scale | Standard Error 0.051 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ethmoid Sinus Posterior | 0.15 score on a scale | Standard Error 0.068 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Maxillary Sinus | 0.12 score on a scale | Standard Error 0.052 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ostiomeatal Complex | -0.31 score on a scale | Standard Error 0.129 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Frontal Sinus | 0.01 score on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Ethmoid Sinus Anterior | 0.07 score on a scale | Standard Error 0.064 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs | Sphenoid Sinus | 0.08 score on a scale | Standard Error 0.069 |
Secondary
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined
Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% The total score for the combined ethmoids and maxillary sinuses can range from 0-30 (0-5 for each left and right of the anterior ethmoid, posterior ethmoid, and maxillary sinuses). The outcome values presented in the results are determined by subtracting the total score at Baseline from the total score at Week 24.
Time frame: Baseline, Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | -1.21 score on a scale | Standard Error 0.43 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | -1.44 score on a scale | Standard Error 0.43 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | -0.19 score on a scale | Standard Error 0.42 |
Secondary
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs
Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% Each sinus pair (left and right side) listed below can achieve a total score of 0-10 (sum of score on each side). The values reported for this outcome calculated by subtracting the score at Baseline from the score at Visit 6 (Wk 24).
Time frame: Baseline, Week 24
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Anterior Ethmoid Sinus Pair | -0.39 score on a scale | Standard Error 0.17 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Posterior Ethmoid Sinus Pair | -0.33 score on a scale | Standard Error 0.18 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Maxillary Sinus Pair | -0.53 score on a scale | Standard Error 0.18 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Frontal Sinus Pair | 0.12 score on a scale | Standard Error 0.2 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Sphenoid Sinus Pair | 0.15 score on a scale | Standard Error 0.2 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Frontal Sinus Pair | -0.16 score on a scale | Standard Error 0.2 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Maxillary Sinus Pair | -0.39 score on a scale | Standard Error 0.17 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Sphenoid Sinus Pair | -0.16 score on a scale | Standard Error 0.19 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Anterior Ethmoid Sinus Pair | -0.53 score on a scale | Standard Error 0.17 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Posterior Ethmoid Sinus Pair | -0.55 score on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Anterior Ethmoid Sinus Pair | -0.19 score on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Posterior Ethmoid Sinus Pair | 0.03 score on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Frontal Sinus Pair | 0.05 score on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Sphenoid Sinus Pair | 0.20 score on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs | Maxillary Sinus Pair | -0.08 score on a scale | Standard Error 0.17 |
Secondary
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations
Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100%
Time frame: Baseline, Week 24
Population: Data provided for full population and CRSwNP, CRSsNP, subjects with prior sinus surgery, and subjects without prior sinus surgery subgroups. Number of participants analyzed in the subgroups will be less than the total overall, as these are only portions of the total population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Total Population | -0.59 score on a scale | Standard Error 0.11 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | CRSwNP | -0.49 score on a scale | Standard Error 0.13 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | CRSsNP | -0.70 score on a scale | Standard Error 0.18 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Subjects with Prior Sinus Surgery | -0.48 score on a scale | Standard Error 0.16 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Subjects without Prior Sinus Surgery | -0.70 score on a scale | Standard Error 0.15 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | CRSwNP | -0.57 score on a scale | Standard Error 0.14 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Subjects without Prior Sinus Surgery | -0.51 score on a scale | Standard Error 0.14 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Subjects with Prior Sinus Surgery | -0.78 score on a scale | Standard Error 0.17 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Total Population | -0.60 score on a scale | Standard Error 0.11 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | CRSsNP | -0.61 score on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Total Population | -0.45 score on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | CRSwNP | -0.30 score on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | CRSsNP | -0.64 score on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Subjects without Prior Sinus Surgery | -0.54 score on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Subjects with Prior Sinus Surgery | -0.33 score on a scale | Standard Error 0.17 |
Secondary
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score
Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within partial opacification and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% for each sinus. Total score ranges from 0 to 50.
Time frame: Baseline, Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score | -0.98 score on a scale | Standard Error 0.65 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score | -1.95 score on a scale | Standard Error 0.64 |
| Placebo | Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score | -0.03 score on a scale | Standard Error 0.65 |
Secondary
Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS)
The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The outcome measured for this study was the EQ VAS, which records the subject's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflects the subject's own judgement. VAS scores range from 0 (worst health you can imagine) to 100 (best health you can imagine).
Time frame: 24 Weeks
Population: Full Analysis Set. Only VAS Scores analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS) | 2.59 score on a scale | Standard Error 1.783 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS) | 3.97 score on a scale | Standard Error 1.791 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS) | -0.35 score on a scale | Standard Error 1.81 |
Secondary
Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)
The SF-36v2 is a multipurpose, 36-item subject-completed validated questionnaire that measures 8 domains of health: physical functioning, role limitations due to physical health (RP), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The SF-36v2 survey with a 4-week recall will be used. It yields scale scores for each of these 8 health domains , each of which is scored from 0 to 100. Higher scores indicate with a better health status, with 100 representing the highest level of functioning possible.
Time frame: 24 Weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Emotional Score | -1.11 score on a scale | Standard Error 1.147 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Bodily Pain Score | 0.94 score on a scale | Standard Error 1.172 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Social Functioning Score | 0.22 score on a scale | Standard Error 1.153 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Vitality Score | 1.13 score on a scale | Standard Error 1.142 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | General Health Score | 0.55 score on a scale | Standard Error 1.091 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Mental Health Score | -0.92 score on a scale | Standard Error 1.169 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Physical Score | 0.92 score on a scale | Standard Error 1.057 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Physical Functioning Score | 1.07 score on a scale | Standard Error 1.039 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Bodily Pain Score | 4.10 score on a scale | Standard Error 1.185 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | General Health Score | 2.38 score on a scale | Standard Error 1.119 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Physical Functioning Score | 1.43 score on a scale | Standard Error 1.055 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Physical Score | 2.64 score on a scale | Standard Error 1.074 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Vitality Score | 3.35 score on a scale | Standard Error 1.156 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Social Functioning Score | 2.05 score on a scale | Standard Error 1.173 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Emotional Score | 1.2 score on a scale | Standard Error 1.169 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Mental Health Score | 0.75 score on a scale | Standard Error 1.188 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Physical Functioning Score | 0.04 score on a scale | Standard Error 1.067 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Social Functioning Score | 1.89 score on a scale | Standard Error 1.181 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Physical Score | 0.16 score on a scale | Standard Error 1.082 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Mental Health Score | -0.69 score on a scale | Standard Error 1.194 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | General Health Score | -1.18 score on a scale | Standard Error 1.21 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Emotional Score | -0.32 score on a scale | Standard Error 1.178 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Vitality Score | 1.81 score on a scale | Standard Error 1.168 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Bodily Pain Score | 1.8 score on a scale | Standard Error 1.201 |
Secondary
Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument
The SF-6D is a single health state index derived from the 11 items from the SF-36v2. SF-6D scores range from 0 (worst health state) to 1 (best health state).
Time frame: 24 Weeks
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument | 0 score on a scale | Standard Error 0.016 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument | 0.04 score on a scale | Standard Error 0.017 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument | 0.01 score on a scale | Standard Error 0.016 |
Secondary
Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS)
The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, with higher scores indicating a worse outcome.
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | -0.24 score on a scale | Standard Error 0.308 |
| OPN-375 372 μg BID | Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | -0.80 score on a scale | Standard Error 0.312 |
| Placebo | Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | -0.62 score on a scale | Standard Error 0.314 |
Secondary
Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores
Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living. The value reported in the results is calculated by subtracting the score reported by the patient at Baseline from the score reported by the patient at Visit 4 (Week 12).
Time frame: 12 Weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.53 score on a scale | Standard Error 0.078 |
| OPN-375 186 μg BID | Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.52 score on a scale | Standard Error 0.077 |
| OPN-375 372 μg BID | Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.61 score on a scale | Standard Error 0.079 |
| OPN-375 372 μg BID | Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.57 score on a scale | Standard Error 0.079 |
| Placebo | Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.48 score on a scale | Standard Error 0.079 |
| Placebo | Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.43 score on a scale | Standard Error 0.078 |
Secondary
Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™
The SIT is a test comprised of 4 booklets each containing 10 microencapsulated (scratch and sniff) odors. Forced choice response alternatives to identify the odor accompany each test item. Each correct response is assigned a score of 1 and incorrect responses are assigned a score of 0. The total score is calculated by summing the scores of each individual odor for a total possible score ranging from 0-40. The higher the score, the better the individual's sense of smell. The test provides an absolute indication of smell loss (anosmia; mild, moderate or severe hyposmia) as well as an index to detect malingering.
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ | 2.47 score on a scale | Standard Error 0.765 |
| OPN-375 372 μg BID | Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ | 2.33 score on a scale | Standard Error 0.768 |
| Placebo | Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ | -1.30 score on a scale | Standard Error 0.793 |
Secondary
Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC)
Global impression of change will be assessed using a subject-completed PGIC scale range: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse
Time frame: Week 4, Week 24
Population: Population size at each timepoint differs based on the number of patients that completed the assessment at the timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OPN-375 186 μg BID | Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) | Week 4 | 84 Participants |
| OPN-375 186 μg BID | Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) | Week 24 | 78 Participants |
| OPN-375 372 μg BID | Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) | Week 4 | 77 Participants |
| OPN-375 372 μg BID | Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) | Week 24 | 80 Participants |
| Placebo | Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) | Week 24 | 56 Participants |
| Placebo | Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) | Week 4 | 57 Participants |
Secondary
Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores
Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours) The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent. The change reported in the results is calculated by subtracting the score reported at Baseline from the score reported at Visit 4 (Week 12).
Time frame: 12 Weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.60 score on a scale | Standard Error 0.078 |
| OPN-375 186 μg BID | Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.54 score on a scale | Standard Error 0.078 |
| OPN-375 372 μg BID | Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.54 score on a scale | Standard Error 0.079 |
| OPN-375 372 μg BID | Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.56 score on a scale | Standard Error 0.08 |
| Placebo | Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores | AM Diary Score | -0.31 score on a scale | Standard Error 0.079 |
| Placebo | Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores | PM Diary Score | -0.32 score on a scale | Standard Error 0.079 |
Secondary
Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)
The PSQI is a validated, self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate 7 component scores (each ranging between 0 and 3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging between 0 and 21. Higher values represent a worse outcome.
Time frame: 12 Weeks, 24 Weeks
Population: Full analysis set. Population sizes differ based on number of patients that completed the assessment at each timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 12 | -0.66 score on a scale | Standard Error 0.291 |
| OPN-375 186 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 24 | -1.12 score on a scale | Standard Error 0.292 |
| OPN-375 372 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 12 | -1.48 score on a scale | Standard Error 0.291 |
| OPN-375 372 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 24 | -1.77 score on a scale | Standard Error 0.294 |
| Placebo | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 24 | -1.09 score on a scale | Standard Error 0.301 |
| Placebo | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 12 | -0.91 score on a scale | Standard Error 0.294 |
Secondary
Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS)
Change from baseline to Week 24/ET on the MCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Time frame: 24 Weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS) | -0.1 score on a scale | Standard Error 0.81 |
| OPN-375 372 μg BID | Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS) | 1.65 score on a scale | Standard Error 0.82 |
| Placebo | Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS) | 1.41 score on a scale | Standard Error 0.834 |
Secondary
Change in the SF-36v2 Physical Composite Score (PCS)
Change from baseline to Week 24/ET on the PCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Time frame: 24 Weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change in the SF-36v2 Physical Composite Score (PCS) | 2.37 score on a scale | Standard Error 0.647 |
| OPN-375 372 μg BID | Change in the SF-36v2 Physical Composite Score (PCS) | 3.64 score on a scale | Standard Error 0.652 |
| Placebo | Change in the SF-36v2 Physical Composite Score (PCS) | 1.58 score on a scale | Standard Error 0.663 |
Secondary
Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ).
The Health and Work Performance Questionnaire measures work productivity (absenteeism and presenteeism). - Absenteeism is measured in missed work days over the past four weeks (range 0-20); absenteeism is measured in % productivity at work (0-100%), with higher values indicating improved productivity. Values for this outcome are reported as the change in relative absenteeism (the percentage of productivity at work) from baseline to Week 24.
Time frame: 24 Weeks
Population: Full analysis set. Population size determined by the number of patients that completed the questionnaire at baseline and Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ). | 0.98 percentage of productivity | Standard Error 2.384 |
| OPN-375 372 μg BID | Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ). | -4.13 percentage of productivity | Standard Error 2.479 |
| Placebo | Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ). | -6.28 percentage of productivity | Standard Error 2.505 |
Secondary
Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery
Outcome value presented here is the percent of subjects who are approved for surgery but no longer elect to undergo a surgery. The number of participants analyzed indicates the total number of participants for whom this analysis was completed.
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OPN-375 186 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery | 52 Participants |
| OPN-375 372 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery | 56 Participants |
| Placebo | Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery | 48 Participants |
Secondary
Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery
Percentage of subjects indicating that they are willing to consider Sinus Surgery
Time frame: Baseline, Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OPN-375 186 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery | Baseline | 63 Participants |
| OPN-375 186 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery | Week 24 | 52 Participants |
| OPN-375 372 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery | Baseline | 59 Participants |
| OPN-375 372 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery | Week 24 | 48 Participants |
| Placebo | Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery | Baseline | 54 Participants |
| Placebo | Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery | Week 24 | 54 Participants |
Secondary
Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention
Percentage of Subjects who meet the minimal objective criteria for surgical intervention
Time frame: Baseline, Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OPN-375 186 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention | Baseline | 42 Participants |
| OPN-375 186 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention | Week 24 | 30 Participants |
| OPN-375 372 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention | Baseline | 48 Participants |
| OPN-375 372 μg BID | Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention | Week 24 | 36 Participants |
| Placebo | Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention | Week 24 | 38 Participants |
| Placebo | Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention | Baseline | 45 Participants |
Secondary
Percentage of Subjects Requiring Rescue Medication After Week 4
Recording of each dose of approved rescue medication after the Week 4 visit through Week 12
Time frame: 8 Weeks
Population: We were unable to complete this analysis due to a misunderstanding on the part of the subjects in the definition of rescue medication. It was confirmed across most countries and sites that subjects indicated use of rescue medication mistakenly, thinking they were being asked to report whether they took the study medication. This data could not be fully reconciled and, therefore, no analysis was completed.
Secondary
Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)
The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, where higher scores indicate a worse outcome.
Time frame: Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | -0.24 score on a scale | Standard Error 0.31 |
| OPN-375 372 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | -0.80 score on a scale | Standard Error 0.31 |
| Placebo | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | -0.62 score on a scale | Standard Error 0.31 |
Secondary
Time Comparison to First Acute Exacerbation of Chronic Sinusitis
Comparing the distribution of time to first acute exacerbation of chronic sinusitis, defined as a worsening of symptoms that requires escalation of treatment
Time frame: 24 Weeks
Population: Number of patients experiencing exacerbation within each treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Time Comparison to First Acute Exacerbation of Chronic Sinusitis | 23.44 Weeks | Standard Error 0.55 |
| OPN-375 372 μg BID | Time Comparison to First Acute Exacerbation of Chronic Sinusitis | 17.19 Weeks | Standard Error 0.25 |
| Placebo | Time Comparison to First Acute Exacerbation of Chronic Sinusitis | 19.73 Weeks | Standard Error 0.69 |
Other Pre-specified
Evaluation of Safety by Recording the Severity of Adverse Events (AEs)
Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe
Time frame: 24 Weeks
Population: Safety Analysis Set - Subjects with at least 1 AE
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OPN-375 186 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Moderate | 29 Participants |
| OPN-375 186 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Severe | 3 Participants |
| OPN-375 186 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Mild | 25 Participants |
| OPN-375 372 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Severe | 3 Participants |
| OPN-375 372 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Mild | 23 Participants |
| OPN-375 372 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Moderate | 26 Participants |
| Placebo | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Severe | 5 Participants |
| Placebo | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Mild | 20 Participants |
| Placebo | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Moderate | 33 Participants |
Other Pre-specified
Evaluation of Safety Measuring Vital Signs- Blood Pressure
Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)
Time frame: 24 Weeks
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Systolic Blood Pressure (mmHg) | 127.3 mmHg | Standard Deviation 14.15 |
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Diastolic Blood Pressure (mmHg) | 78.0 mmHg | Standard Deviation 8.22 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Diastolic Blood Pressure (mmHg) | 78.2 mmHg | Standard Deviation 9.7 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Systolic Blood Pressure (mmHg) | 126.7 mmHg | Standard Deviation 14.11 |
| Placebo | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Diastolic Blood Pressure (mmHg) | 79.3 mmHg | Standard Deviation 8.62 |
| Placebo | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Systolic Blood Pressure (mmHg) | 127.3 mmHg | Standard Deviation 14.69 |
Other Pre-specified
Evaluation of Safety Measuring Vital Signs- Pulse
Measure pulse in beats per minute (bpm)
Time frame: 24 Weeks
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Pulse | 73.7 Beats per minute | Standard Deviation 11.96 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Pulse | 72.7 Beats per minute | Standard Deviation 9.5 |
| Placebo | Evaluation of Safety Measuring Vital Signs- Pulse | 73.1 Beats per minute | Standard Deviation 9.45 |
Other Pre-specified
Evaluation of Safety Measuring Vital Signs- Weight
Assessment of safety from physical examination-weight measured in kg or lb
Time frame: 24 Weeks
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Weight | 82.81 kg | Standard Deviation 20.873 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Weight | 84.23 kg | Standard Deviation 19.232 |
| Placebo | Evaluation of Safety Measuring Vital Signs- Weight | 83.84 kg | Standard Deviation 21.531 |
Other Pre-specified
Evaluation of Safety - Monitoring Concomitant Medication Usage
Assessment for safety from the collection of information for concomitant medications usage
Time frame: 24 Weeks
Population: Number of subjects receiving concomitant medications. Only top 5 con-meds are detailed below.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Allergen Extracts | 6 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Ace Inhibitors, Plain | 5 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Amides | 33 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Adrenergics in Combination with Corticosteroids or other drugs | 35 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Alpha-Adrenoreceptor Antagonists | 1 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Ace Inhibitors, Plain | 7 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Amides | 38 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Adrenergics in Combination with Corticosteroids or other drugs | 30 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Allergen Extracts | 6 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Alpha-Adrenoreceptor Antagonists | 6 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Alpha-Adrenoreceptor Antagonists | 2 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Allergen Extracts | 2 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Amides | 30 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Ace Inhibitors, Plain | 12 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Adrenergics in Combination with Corticosteroids or other drugs | 27 Participants |
Other Pre-specified
Evaluation of Safety-Nasal Examination
Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum.
Time frame: 24 Weeks
Population: Safety Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | Present | 3 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | Absent | 105 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Septal Erosion/Perforation | Present | 3 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Septal Erosion/Perforation | Absent | 105 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion (non-septum) | Present | 0 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion (non-septum) | Absent | 108 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Mucosal Candidiasis | Present | 0 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Mucosal Candidiasis | Absent | 108 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion (non-septum) | Absent | 103 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | Present | 9 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion (non-septum) | Present | 2 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Mucosal Candidiasis | Present | 0 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Mucosal Candidiasis | Absent | 105 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Septal Erosion/Perforation | Present | 3 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | Absent | 96 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Septal Erosion/Perforation | Absent | 102 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Epistaxis | Absent | 102 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Septal Erosion/Perforation | Absent | 103 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Mucosal Candidiasis | Present | 0 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Ulceration/Erosion (non-septum) | Present | 1 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Mucosal Candidiasis | Absent | 103 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Epistaxis | Present | 1 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Ulceration/Erosion (non-septum) | Absent | 102 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Septal Erosion/Perforation | Present | 0 Participants |