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 (CRS) 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 the average morning 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
1. men or women aged 18 years and older at baseline visit 2. women of child bearing 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 sinusitis 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 or purulent discharge; or polyps/polypoid tissue \<Grade 1 in middle meatus, bilaterally 6. must have confirmatory evidence via a computed tomography(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 correctly; all subjects will be required to demonstrate correct use with the practice exhalation delivery system (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.
Exclusion criteria
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 polyp grade ≥1 (polyp that is free on 5 sides and has a stalk) on either side of the nose 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 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 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 chronic sinusitis 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, intraarticular, 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 elevation on any form of steroid therapy 28. history or current diagnosis of the presence (in either eye) of a subcapsular cataract 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) inhibitors (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole) 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 care professional 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 (APOV) 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 |
|---|---|---|
| Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the 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 each of the left and right ostiomeatal complex (OMC). The values reported for this outcome are the change in total opacification of the left an dright 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 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 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 sever 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 | 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). The values provided in the outcome data are calculated by subtracting the score reported at baseline from the score reported at Visit 6 (Week 24). |
| Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24 | Baseline, Week 24 | Percentage of subjects indicating that they are willing to consider Sinus Surgery. This is a comparison of health economic measures and data was obtained by direct questioning of the subjects during study visits. |
| Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24. | Baseline, Week 24 | Percentage of subjects who meet the minimal objective criteria for surgical intervention based on completion of a surgical intervention assessment questionnaire for the investigator. |
| 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. Number of participants analyzed indicates the total number of participants for whom this analysis was completed. |
| Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Baseline, Week 4 | The 4 individual CRS symptoms are: congestion, facial pain or pressure sensation, nasal discharge (anterior and/or posterior), and sense of smell. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. The scores at baseline and week 4 are calculated by averaging the score reported for the individual symptom over 7 days prior to the timepoint. The value provided in the results is calculated by subtracting the score at Week 4 from the score at Baseline; therefore, scores reported here can range from -3 to 3. |
| Time to First Acute Exacerbation of Chronic Sinusitis | 24 Weeks | Comparing the distribution of time to first acute exacerbation of chronic sinusitis across treatment groups. An exacerbation of chronic sinusitis is defined as a worsening of symptoms that requires escalation of treatment. |
| Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | 24 Weeks | 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, extra-nasal rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. The score range for each domain are as follows: Rhinologic: 0-30; Extra-nasal rhinologic: 0-15; Ear/facial: 0-25; Psychological dysfunction: 0-35; Sleep dysfunction: 0-25. 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, and total scores are calculated by adding scores together. The values reported here are calculated by subtracting the score reported at baseline from the score reported at Week 24 and, therefore, can range from the negative maximum score value to the positive maximum score value. |
| Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | 8 weeks, 12 weeks. | 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. Range of scores for each symptom is 0=none, 1=mild, 2=moderate, 3=severe. The composite score is the sum of the 3 symptom scores and will range from 0-9. Scores reported at each timepoint are the averaged total instantaneous AM scores over the last 7 days before the given timepoint. The values presented here are calculated by subtracting the score at Baseline from Week 8 and Week 12, respectively. |
| Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | 8 Weeks; 12 Weeks | Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. 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 From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Baseline, Week 8, Week 12 | Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) scores. 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 From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Baseline, Week 8, Week 12 | Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. 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 From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Baseline, Week 8, Week 12 | Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent. |
| Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery | 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 for subgroups in patients without and without previous sinus surgery. Percent volume opacified of the combined ethmoid and maxillary sinuses can range from 0% to 100%. Outcome measure is 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%. |
| 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 Scores for Each Sinus Pair | 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). 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 (week 24). |
| Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment. | Baseline, Week 24 | Percent volume opacified of the worst maxillary sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst maxillary sinus at baseline to the percent opacification of the same maxillary sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%. |
| Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment. | 24 weeks | Percent volume opacified of the worst ethmoid sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst ethmoid sinus at baseline to the percent opacification of the same ethmoid sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%. |
| Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment. | 24 weeks | Percent volume opacified of the worst sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst sinus at baseline to the percent opacification of the same sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%. |
| Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score | Baseline, Week 24 | Zinreich 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 each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal). Total score ranges from 0 to 50. |
| Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Baseline, Week 24 | Zinreich Modification of the Lund-Mackay Staging System: Zinreich 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 of the following sinus pairs can achieve a total score of 0-10 (sum of score on each left and right side): anterior ethmoids, posterior ethmoids, maxillary sinuses, frontal sinuses, sphenoid sinuses. The values reported for this outcome are calculated by subtracting the score at baseline from the score at Visit 6 (Wk 24). |
| Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | 24 weeks | Zinreich Modification of the Lund-Mackay Staging System: Zinreich modified the LM system by creating subdivisions with 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 were determined by subtracting the total score at Baseline from the total score at Week 24. |
| Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | 24 Weeks | Zinreich Modification of the Lund-Mackay Staging System: Zinreich modified the LM system by creating subdivisions with 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%. Data provided for full population and with and 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. |
| 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. Values provided for this outcome measure are the percentage of subjects reporting a score of 1 - Very much improved, 2 - Much improved, or 3 - Minimally improved at each timepoint. |
| 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 a better health status, with 100 representing the highest level of functioning possible. |
| Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component 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. Result values are calculated by subtracting the score reported at Week 24 from the score reported at Baseline. |
| Change in the SF-36v2 Physical Component 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. Result values are calculated by subtracting the score reported at Week 24 from the score reported at Baseline. |
| 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, where higher scores indicate a worse outcome. |
| Severity of Depression at Week 24 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, where higher scores indicate a worse outcome. Results reported for this outcome measure are the |
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. Top 5 reported con-meds by therapeutic class are listed for this outcome. |
| 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
Australia, Bulgaria, Czechia, Georgia, New Zealand, Poland, Romania, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo BID x 24 Weeks
OPN-375: OPN-375, BID | 75 |
| OPN-375 186 μg BID OPN-375 186 μg BID x 24 Weeks
OPN-375: OPN-375, BID | 73 |
| OPN-375 372 μg BID OPN-375 372 μg BID x 24 Weeks
OPN-375: OPN-375, BID | 74 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Marked Randomized in error (patient did not receive study drug) | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | OPN-375 186 μg BID | Placebo | OPN-375 372 μg BID | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 8 Participants | 11 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 67 Participants | 63 Participants | 195 Participants |
| Age, Continuous | 47.1 years STANDARD_DEVIATION 13.75 | 48.7 years STANDARD_DEVIATION 12.34 | 49.4 years STANDARD_DEVIATION 13.53 | 48.4 years STANDARD_DEVIATION 13.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 74 Participants | 74 Participants | 219 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Beclomethasone | 2 participants | 2 participants | 2 participants | 6 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Budesonide | 3 participants | 7 participants | 2 participants | 12 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Fluticasone and azelastine | 13 participants | 14 participants | 13 participants | 40 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Fluticasone furoate | 23 participants | 28 participants | 24 participants | 75 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Fluticasone proprionate | 15 participants | 20 participants | 16 participants | 51 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Mometasone furoate | 28 participants | 38 participants | 35 participants | 101 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Other | 2 participants | 2 participants | 2 participants | 6 participants |
| Intranasal corticosteroid treatment for chronic sinusitis within last 10 years Triamcinolone | 2 participants | 2 participants | 1 participants | 5 participants |
| Other Chronic Sinusitis Treatment History Plan to continue on saline lavage during study (decided at baseline visit) | 15 participants | 20 participants | 13 participants | 48 participants |
| Other Chronic Sinusitis Treatment History Systemic antibiotic in last 5 years | 10 participants | 19 participants | 19 participants | 48 participants |
| Prior Sinusitis Surgery Any Surgery | 30 participants | 32 participants | 31 participants | 93 participants |
| Prior Sinusitis Surgery Balloon sinuplasty | 0 participants | 0 participants | 1 participants | 1 participants |
| Prior Sinusitis Surgery Endoscopic sinus surgery | 28 participants | 26 participants | 30 participants | 84 participants |
| Prior Sinusitis Surgery Other surgery | 3 participants | 7 participants | 7 participants | 17 participants |
| Prior Sinusitis Surgery Polypectomy alone | 2 participants | 5 participants | 7 participants | 14 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 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 | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 72 Participants | 74 Participants | 73 Participants | 219 Participants |
| Region of Enrollment Australia | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Bulgaria | 6 Participants | 6 Participants | 4 Participants | 16 Participants |
| Region of Enrollment Czechia | 4 Participants | 9 Participants | 5 Participants | 18 Participants |
| Region of Enrollment Georgia | 8 Participants | 7 Participants | 7 Participants | 22 Participants |
| Region of Enrollment New Zealand | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Poland | 37 Participants | 36 Participants | 30 Participants | 103 Participants |
| Region of Enrollment Romania | 9 Participants | 6 Participants | 9 Participants | 24 Participants |
| Region of Enrollment Spain | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 5 Participants | 5 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Female | 40 Participants | 32 Participants | 39 Participants | 111 Participants |
| Sex: Female, Male Male | 33 Participants | 43 Participants | 35 Participants | 111 Participants |
| Sinus Imaging in last year CT Scans 0 | 25 Participants | 31 Participants | 32 Participants | 88 Participants |
| Sinus Imaging in last year CT Scans 1 | 46 Participants | 41 Participants | 41 Participants | 128 Participants |
| Sinus Imaging in last year CT Scans 2 | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Sinus Imaging in last year CT Scans 3 | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sinus Imaging in last year MRI Scans 0 | 73 Participants | 71 Participants | 71 Participants | 215 Participants |
| Sinus Imaging in last year MRI Scans 1 | 0 Participants | 4 Participants | 3 Participants | 7 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 | 12 participants | 6 participants | 4 participants | 22 participants |
| Smoking History Current Smoker (other forms of tobacco) | 0 participants | 0 participants | 0 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 73 | 0 / 74 |
| other Total, other adverse events | 31 / 75 | 17 / 73 | 43 / 74 |
| serious Total, serious adverse events | 0 / 75 | 1 / 73 | 4 / 74 |
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 |
|---|---|---|---|
| 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 | -0.81 score on a scale | Standard Error 0.202 |
| 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 | -1.54 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) at the End of Week 4 | -1.74 score on a scale | Standard Error 0.204 |
Primary
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) 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 |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses. | 1.19 percentage of opacification | Standard Error 1.74 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses. | -7.00 percentage of opacification | Standard Error 1.725 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses. | -5.14 percentage of opacification | Standard Error 1.742 |
Secondary
Change From Baseline to Defined Timepoints - 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, extra-nasal rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. The score range for each domain are as follows: Rhinologic: 0-30; Extra-nasal rhinologic: 0-15; Ear/facial: 0-25; Psychological dysfunction: 0-35; Sleep dysfunction: 0-25. 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, and total scores are calculated by adding scores together. The values reported here are calculated by subtracting the score reported at baseline from the score reported at Week 24 and, therefore, can range from the negative maximum score value to the positive maximum score value.
Time frame: 24 Weeks
Population: Full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Rhinologic Symptoms Domain Score | -2.47 score on a scale | Standard Error 0.649 |
| Placebo | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Total Score | -8.72 score on a scale | Standard Error 2.186 |
| Placebo | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Extra-Nasal Rhinologic Symptoms Domain Score | -1.61 score on a scale | Standard Error 0.411 |
| Placebo | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Ear/Facial Symptoms Domain Score | -1.31 score on a scale | Standard Error 0.613 |
| Placebo | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Psychological Dysfunction Domain Score | -1.80 score on a scale | Standard Error 0.951 |
| Placebo | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Sleep Dysfunction Domain Score | -1.77 score on a scale | Standard Error 0.62 |
| OPN-375 186 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Sleep Dysfunction Domain Score | -4.84 score on a scale | Standard Error 0.622 |
| OPN-375 186 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Psychological Dysfunction Domain Score | -5.81 score on a scale | Standard Error 0.955 |
| OPN-375 186 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Total Score | -19.45 score on a scale | Standard Error 2.197 |
| OPN-375 186 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Ear/Facial Symptoms Domain Score | -4.45 score on a scale | Standard Error 0.616 |
| OPN-375 186 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Rhinologic Symptoms Domain Score | -5.25 score on a scale | Standard Error 0.653 |
| OPN-375 186 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Extra-Nasal Rhinologic Symptoms Domain Score | -2.84 score on a scale | Standard Error 0.413 |
| OPN-375 372 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Rhinologic Symptoms Domain Score | -4.77 score on a scale | Standard Error 0.656 |
| OPN-375 372 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Extra-Nasal Rhinologic Symptoms Domain Score | -2.45 score on a scale | Standard Error 0.415 |
| OPN-375 372 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Sleep Dysfunction Domain Score | -3.61 score on a scale | Standard Error 0.626 |
| OPN-375 372 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Ear/Facial Symptoms Domain Score | -3.18 score on a scale | Standard Error 0.619 |
| OPN-375 372 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Total Score | -15.54 score on a scale | Standard Error 2.219 |
| OPN-375 372 μg BID | Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains | Psychological Dysfunction Domain Score | -4.16 score on a scale | Standard Error 0.965 |
Secondary
Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment.
Percent volume opacified of the worst ethmoid sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst ethmoid sinus at baseline to the percent opacification of the same ethmoid sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%.
Time frame: 24 weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment. | -2.79 percentage of opacification | Standard Error 1.928 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment. | -9.65 percentage of opacification | Standard Error 1.92 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment. | -6.82 percentage of opacification | Standard Error 1.928 |
Secondary
Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment.
Percent volume opacified of the worst maxillary sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst maxillary sinus at baseline to the percent opacification of the same maxillary sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%.
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment. | -5.83 percentage of opacification | Standard Error 2.734 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment. | -14.50 percentage of opacification | Standard Error 2.708 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment. | -10.21 percentage of opacification | Standard Error 2.724 |
Secondary
Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment.
Percent volume opacified of the worst sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst sinus at baseline to the percent opacification of the same sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%.
Time frame: 24 weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment. | -6.07 percentage of opacification | Standard Error 2.493 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment. | -14.02 percentage of opacification | Standard Error 2.439 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment. | -10.75 percentage of opacification | Standard Error 2.448 |
Secondary
Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery
Change from Baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT for subgroups in patients without and without previous sinus surgery. Percent volume opacified of the combined ethmoid and maxillary sinuses can range from 0% to 100%. Outcome measure is 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 population sizes provided as overall number of participants analyzed. Subgroup population sizes provided with each set of results below.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery | Patients with prior sinus surgery | 3.89 percentage of opacification | Standard Error 2.882 |
| Placebo | Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery | Patients without prior sinus surgery | -0.53 percentage of opacification | Standard Error 2.118 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery | Patients with prior sinus surgery | -5.86 percentage of opacification | Standard Error 2.862 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery | Patients without prior sinus surgery | -7.83 percentage of opacification | Standard Error 2.129 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery | Patients with prior sinus surgery | -6.73 percentage of opacification | Standard Error 2.873 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery | Patients without prior sinus surgery | -4.50 percentage of opacification | Standard Error 2.166 |
Secondary
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair
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). 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 (week 24).
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Frontal Sinus Pair | 0.11 score on a scale | Standard Error 0.093 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Maxillary Sinus Pair | 0.04 score on a scale | Standard Error 0.052 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Anterior Ethmoid Pair | 0.17 score on a scale | Standard Error 0.071 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Posterior Ethmoid Pair | 0.11 score on a scale | Standard Error 0.071 |
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Sphenoid Sinus Pair | 0.19 score on a scale | Standard Error 0.078 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Maxillary Sinus Pair | 0.01 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 Scores for Each Sinus Pair | Anterior Ethmoid Pair | 0.03 score on a scale | Standard Error 0.071 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Posterior Ethmoid Pair | 0.04 score on a scale | Standard Error 0.071 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Frontal Sinus Pair | -0.12 score on a scale | Standard Error 0.091 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Sphenoid Sinus Pair | -0.04 score on a scale | Standard Error 0.077 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Sphenoid Sinus Pair | 0.03 score on a scale | Standard Error 0.078 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Frontal Sinus Pair | -0.03 score on a scale | Standard Error 0.092 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Anterior Ethmoid Pair | 0.02 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 Scores for Each Sinus Pair | Maxillary Sinus Pair | 0.09 score on a scale | Standard Error 0.049 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair | Posterior Ethmoid Pair | -0.04 score on a scale | Standard Error 0.071 |
Secondary
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the 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 each of the left and right ostiomeatal complex (OMC). The values reported for this outcome are the change in total opacification of the left an dright 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 |
|---|---|---|---|
| Placebo | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined | 0.34 score on a scale | Standard Error 0.162 |
| OPN-375 186 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined | 0.09 score on a scale | Standard Error 0.16 |
| OPN-375 372 μg BID | Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined | 0.04 score on a scale | Standard Error 0.16 |
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 |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score | 0.77 score on a scale | Standard Error 0.332 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score | -0.54 score on a scale | Standard Error 0.327 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score | -0.33 score on a scale | Standard Error 0.329 |
Secondary
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined
Zinreich Modification of the Lund-Mackay Staging System: Zinreich modified the LM system by creating subdivisions with 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 were determined by subtracting the total score at Baseline from the total score at Week 24.
Time frame: 24 weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | 0.51 score on a scale | Standard Error 0.568 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | -1.78 score on a scale | Standard Error 0.54 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined | -1.25 score on a scale | Standard Error 0.546 |
Secondary
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs.
Zinreich Modification of the Lund-Mackay Staging System: Zinreich 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 of the following sinus pairs can achieve a total score of 0-10 (sum of score on each left and right side): anterior ethmoids, posterior ethmoids, maxillary sinuses, frontal sinuses, sphenoid sinuses. The values reported for this outcome are calculated by subtracting the score at baseline from the score at Visit 6 (Wk 24).
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Frontal Sinus Pair | 0.11 score on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Maxillary Sinus Pair | 0.17 score on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Anterior Ethmoid Sinus Pair | 0.18 score on a scale | Standard Error 0.218 |
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Posterior Ethmoid Sinus Pair | 0.18 score on a scale | Standard Error 0.239 |
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Sphenoid Sinus Pair | 0.46 score on a scale | Standard Error 0.249 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Maxillary Sinus Pair | -0.54 score on a scale | Standard Error 0.2 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Anterior Ethmoid Sinus Pair | -0.73 score on a scale | Standard Error 0.215 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Posterior Ethmoid Sinus Pair | -0.54 score on a scale | Standard Error 0.234 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Frontal Sinus Pair | -0.37 score on a scale | Standard Error 0.245 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Sphenoid Sinus Pair | -0.32 score on a scale | Standard Error 0.239 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Sphenoid Sinus Pair | 0.02 score on a scale | Standard Error 0.243 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Frontal Sinus Pair | 0.00 score on a scale | Standard Error 0.246 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Anterior Ethmoid Sinus Pair | -0.48 score on a scale | Standard Error 0.217 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Maxillary Sinus Pair | -0.36 score on a scale | Standard Error 0.202 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs. | Posterior Ethmoid Sinus Pair | -0.41 score on a scale | Standard Error 0.236 |
Secondary
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations
Zinreich Modification of the Lund-Mackay Staging System: Zinreich modified the LM system by creating subdivisions with 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%. Data provided for full population and with and 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.
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Prior sinus surgery subgroup | -0.37 score on a scale | Standard Error 0.228 |
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Total population | -0.36 score on a scale | Standard Error 0.137 |
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Without prior sinus surgery subgroup | -0.37 score on a scale | Standard Error 0.165 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Prior sinus surgery subgroup | -0.70 score on a scale | Standard Error 0.223 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Total population | -0.93 score on a scale | Standard Error 0.135 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Without prior sinus surgery subgroup | -1.06 score on a scale | Standard Error 0.167 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Total population | -0.55 score on a scale | Standard Error 0.135 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Without prior sinus surgery subgroup | -0.52 score on a scale | Standard Error 0.168 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations | Prior sinus surgery subgroup | -0.64 score on a scale | Standard Error 0.225 |
Secondary
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score
Zinreich 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 each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal). Total score ranges from 0 to 50.
Time frame: Baseline, Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score | 0.73 score on a scale | Standard Error 0.815 |
| OPN-375 186 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score | -2.44 score on a scale | Standard Error 0.806 |
| OPN-375 372 μg BID | Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score | -1.45 score on a scale | Standard Error 0.816 |
Secondary
Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous).
The 4 individual CRS symptoms are: congestion, facial pain or pressure sensation, nasal discharge (anterior and/or posterior), and sense of smell. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. The scores at baseline and week 4 are calculated by averaging the score reported for the individual symptom over 7 days prior to the timepoint. The value provided in the results is calculated by subtracting the score at Week 4 from the score at Baseline; therefore, scores reported here can range from -3 to 3.
Time frame: Baseline, Week 4
Population: Full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Facial Pain/Pressure | -0.28 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Congestion/Obstruction | -0.26 score on a scale | Standard Error 0.076 |
| Placebo | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Nasal Discharge | -0.27 score on a scale | Standard Error 0.076 |
| Placebo | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Sense of Smell | -0.13 score on a scale | Standard Error 0.066 |
| OPN-375 186 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Congestion/Obstruction | -0.60 score on a scale | Standard Error 0.077 |
| OPN-375 186 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Nasal Discharge | -0.52 score on a scale | Standard Error 0.076 |
| OPN-375 186 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Sense of Smell | -0.24 score on a scale | Standard Error 0.067 |
| OPN-375 186 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Facial Pain/Pressure | -0.44 score on a scale | Standard Error 0.081 |
| OPN-375 372 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Facial Pain/Pressure | -0.51 score on a scale | Standard Error 0.081 |
| OPN-375 372 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Congestion/Obstruction | -0.70 score on a scale | Standard Error 0.077 |
| OPN-375 372 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Sense of Smell | -0.36 score on a scale | Standard Error 0.067 |
| OPN-375 372 μg BID | Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous). | Nasal Discharge | -0.55 score on a scale | Standard Error 0.077 |
Secondary
Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery.
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. Range of scores for each symptom is 0=none, 1=mild, 2=moderate, 3=severe. The composite score is the sum of the 3 symptom scores and will range from 0-9. Scores reported at each timepoint are the averaged total instantaneous AM scores over the last 7 days before the given timepoint. The values presented here are calculated by subtracting the score at Baseline from Week 8 and Week 12, respectively.
Time frame: 8 weeks, 12 weeks.
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change Total Population | -1.20 score on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change Total Population | -1.55 score on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change With Prior Surgery Population | -1.28 score on a scale | Standard Error 0.347 |
| Placebo | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change With Prior Surgery Population | -1.58 score on a scale | Standard Error 0.361 |
| Placebo | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change Without Prior Surgery Population | -1.13 score on a scale | Standard Error 0.263 |
| Placebo | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change Without Prior Surgery Population | -1.51 score on a scale | Standard Error 0.276 |
| OPN-375 186 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change Without Prior Surgery Population | -2.30 score on a scale | Standard Error 0.273 |
| OPN-375 186 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change Total Population | -2.02 score on a scale | Standard Error 0.212 |
| OPN-375 186 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change With Prior Surgery Population | -2.76 score on a scale | Standard Error 0.379 |
| OPN-375 186 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change Without Prior Surgery Population | -1.86 score on a scale | Standard Error 0.26 |
| OPN-375 186 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change Total Population | -2.47 score on a scale | Standard Error 0.223 |
| OPN-375 186 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change With Prior Surgery Population | -2.28 score on a scale | Standard Error 0.355 |
| OPN-375 372 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change Total Population | -2.60 score on a scale | Standard Error 0.223 |
| OPN-375 372 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change With Prior Surgery Population | -1.95 score on a scale | Standard Error 0.355 |
| OPN-375 372 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change Without Prior Surgery Population | -2.70 score on a scale | Standard Error 0.274 |
| OPN-375 372 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 12 Change With Prior Surgery Population | -2.36 score on a scale | Standard Error 0.375 |
| OPN-375 372 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change Total Population | -2.19 score on a scale | Standard Error 0.212 |
| OPN-375 372 μg BID | Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery. | Week 8 Change Without Prior Surgery Population | -2.28 score on a scale | Standard Error 0.26 |
Secondary
Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores
Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. 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: Baseline, Week 8, Week 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.41 score on a scale | Standard Error 0.084 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.41 score on a scale | Standard Error 0.085 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.55 score on a scale | Standard Error 0.089 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.53 score on a scale | Standard Error 0.089 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.77 score on a scale | Standard Error 0.091 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.63 score on a scale | Standard Error 0.085 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.77 score on a scale | Standard Error 0.09 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.66 score on a scale | Standard Error 0.086 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.78 score on a scale | Standard Error 0.091 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.70 score on a scale | Standard Error 0.086 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.78 score on a scale | Standard Error 0.091 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.67 score on a scale | Standard Error 0.085 |
Secondary
Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores
Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. 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: 8 Weeks; 12 Weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in AM Score - Week 12 | -0.52 score on a scale | Standard Error 0.081 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in AM Score - Week 8 | -0.40 score on a scale | Standard Error 0.078 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in PM Score - Week 12 | -0.50 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in PM Score - Week 8 | -0.35 score on a scale | Standard Error 0.081 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in AM Score - Week 12 | -0.88 score on a scale | Standard Error 0.082 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in PM Score - Week 8 | -0.69 score on a scale | Standard Error 0.082 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in AM Score - Week 8 | -0.76 score on a scale | Standard Error 0.079 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in PM Score - Week 12 | -0.85 score on a scale | Standard Error 0.081 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in PM Score - Week 8 | -0.75 score on a scale | Standard Error 0.082 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in AM Score - Week 8 | -0.84 score on a scale | Standard Error 0.079 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in PM Score - Week 12 | -0.91 score on a scale | Standard Error 0.082 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores | Change in AM Score - Week 12 | -0.97 score on a scale | Standard Error 0.082 |
Secondary
Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores
Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) scores. 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: Baseline, Week 8, Week 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.39 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.35 score on a scale | Standard Error 0.081 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.49 score on a scale | Standard Error 0.085 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.51 score on a scale | Standard Error 0.085 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.83 score on a scale | Standard Error 0.086 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.63 score on a scale | Standard Error 0.08 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.83 score on a scale | Standard Error 0.086 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.66 score on a scale | Standard Error 0.082 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.86 score on a scale | Standard Error 0.087 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.68 score on a scale | Standard Error 0.082 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.85 score on a scale | Standard Error 0.086 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.68 score on a scale | Standard Error 0.08 |
Secondary
Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores
Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent.
Time frame: Baseline, Week 8, Week 12
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.13 score on a scale | Standard Error 0.081 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.32 score on a scale | Standard Error 0.086 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.18 score on a scale | Standard Error 0.082 |
| Placebo | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.29 score on a scale | Standard Error 0.085 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.35 score on a scale | Standard Error 0.082 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.39 score on a scale | Standard Error 0.083 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.49 score on a scale | Standard Error 0.087 |
| OPN-375 186 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.46 score on a scale | Standard Error 0.086 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 12 | -0.63 score on a scale | Standard Error 0.087 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in AM Score - Week 8 | -0.55 score on a scale | Standard Error 0.083 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 8 | -0.51 score on a scale | Standard Error 0.082 |
| OPN-375 372 μg BID | Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores | Change in PM Score - Week 12 | -0.55 score on a scale | Standard Error 0.086 |
Secondary
Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument | 2.10 score on a scale | Standard Error 1.889 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument | 9.67 score on a scale | Standard Error 1.88 |
| OPN-375 372 μg BID | Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument | 7.30 score on a scale | Standard Error 1.891 |
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 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 |
|---|---|---|---|---|
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Physical Functioning Score | 0.54 score on a scale | Standard Error 1.012 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Physical Score | 0.18 score on a scale | Standard Error 1.018 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Bodily Pain Score | 2.46 score on a scale | Standard Error 1.193 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | General Health Score | -0.20 score on a scale | Standard Error 1.01 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Vitality Score | 0.35 score on a scale | Standard Error 1.12 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Social Functioning Score | -0.11 score on a scale | Standard Error 1.173 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Role Emotional Score | -0.77 score on a scale | Standard Error 1.133 |
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) | Mental Health score | -1.70 score on a scale | Standard Error 1.1 |
| 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 | 5.74 score on a scale | Standard Error 1.205 |
| 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 | 2.23 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) | General Health Score | 4.71 score on a scale | Standard Error 1.025 |
| 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 | 4.59 score on a scale | Standard Error 1.129 |
| 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 | 4.70 score on a scale | Standard Error 1.186 |
| 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 | 3.46 score on a scale | Standard Error 1.023 |
| 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 | 5.02 score on a scale | Standard Error 1.029 |
| 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 | 2.26 score on a scale | Standard Error 1.112 |
| 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 | 3.54 score on a scale | Standard Error 1.223 |
| 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 | 3.73 score on a scale | Standard Error 1.049 |
| 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 | 2.24 score on a scale | Standard Error 1.043 |
| 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 | 2.78 score on a scale | Standard Error 1.037 |
| 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 | 0.42 score on a scale | Standard Error 1.167 |
| 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 | 1.58 score on a scale | Standard Error 1.204 |
| 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 | 3.98 score on a scale | Standard Error 1.157 |
| 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 | 1.23 score on a scale | Standard Error 1.138 |
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). The values provided in the outcome data are calculated by subtracting the score reported at baseline from the score reported at Visit 6 (Week 24).
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument | 0.00 score on a scale | Standard Error 0.016 |
| OPN-375 186 μg BID | Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument | 0.06 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 | 0.05 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, where higher scores indicate a worse outcome.
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 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) | -0.23 score on a scale | Standard Error 0.306 |
| 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) | -0.74 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) | -0.20 score on a scale | Standard Error 0.312 |
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 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 sever hyposmia) as well as an index to detect malingering.
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ | 0.23 score on a scale | Standard Error 0.954 |
| OPN-375 186 μg BID | Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ | 2.63 score on a scale | Standard Error 0.959 |
| OPN-375 372 μg BID | Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ | 0.70 score on a scale | Standard Error 0.972 |
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. Values provided for this outcome measure are the percentage of subjects reporting a score of 1 - Very much improved, 2 - Much improved, or 3 - Minimally improved at each timepoint.
Time frame: Week 4, Week 24
Population: Full analysis set provided as overall number of participants. Number analyzed at each timepoint is the total number of responders at that timepoint.
| Arm | Measure | Group | Value (COUNT_OF_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 | 37 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 | 42 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 | 47 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 | 59 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 | 56 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 | 63 Participants |
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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 12 | -0.27 score on a scale | Standard Error 0.306 |
| Placebo | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 24 | -0.33 score on a scale | Standard Error 0.293 |
| OPN-375 186 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 12 | -1.18 score on a scale | Standard Error 0.31 |
| OPN-375 186 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 24 | -2.01 score on a scale | Standard Error 0.298 |
| OPN-375 372 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 12 | -1.12 score on a scale | Standard Error 0.307 |
| OPN-375 372 μg BID | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Week 24 | -1.08 score on a scale | Standard Error 0.295 |
Secondary
Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component 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. Result values are calculated by subtracting the score reported at Week 24 from the score reported at Baseline.
Time frame: 24 Weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS). | -0.82 score on a scale | Standard Error 0.888 |
| OPN-375 186 μg BID | Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS). | 2.25 score on a scale | Standard Error 0.895 |
| OPN-375 372 μg BID | Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS). | 1.17 score on a scale | Standard Error 0.913 |
Secondary
Change in the SF-36v2 Physical Component 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. Result values are calculated by subtracting the score reported at Week 24 from the score reported at Baseline.
Time frame: 24 Weeks
Population: full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the SF-36v2 Physical Component Score (PCS) | 2.12 score on a scale | Standard Error 0.712 |
| OPN-375 186 μg BID | Change in the SF-36v2 Physical Component Score (PCS) | 5.35 score on a scale | Standard Error 0.723 |
| OPN-375 372 μg BID | Change in the SF-36v2 Physical Component Score (PCS) | 4.34 score on a scale | Standard Error 0.738 |
Secondary
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. Number of participants analyzed indicates the total number of participants for whom this analysis was completed.
Time frame: Week 24
Population: Total number of responders in each treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery | 35 Participants |
| OPN-375 186 μg BID | Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery | 33 Participants |
| OPN-375 372 μg BID | Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery | 36 Participants |
Secondary
Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24
Percentage of subjects indicating that they are willing to consider Sinus Surgery. This is a comparison of health economic measures and data was obtained by direct questioning of the subjects during study visits.
Time frame: Baseline, Week 24
Population: Overall number of participants analyzed is total number of responders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24 | Baseline | 38 Participants |
| Placebo | Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24 | Week 24 | 35 Participants |
| OPN-375 186 μg BID | Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24 | Baseline | 40 Participants |
| OPN-375 186 μg BID | Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24 | Week 24 | 36 Participants |
| OPN-375 372 μg BID | Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24 | Baseline | 38 Participants |
| OPN-375 372 μg BID | Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24 | Week 24 | 33 Participants |
Secondary
Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24.
Percentage of subjects who meet the minimal objective criteria for surgical intervention based on completion of a surgical intervention assessment questionnaire for the investigator.
Time frame: Baseline, Week 24
Population: Overall number of participants analyzed is total number of responders in each treatment group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24. | Baseline | 15 Participants |
| Placebo | Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24. | Week 24 | 14 Participants |
| OPN-375 186 μg BID | Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24. | Baseline | 6 Participants |
| OPN-375 186 μg BID | Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24. | Week 24 | 3 Participants |
| OPN-375 372 μg BID | Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24. | Baseline | 15 Participants |
| OPN-375 372 μg BID | Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24. | Week 24 | 10 Participants |
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. Results reported for this outcome measure are the
Time frame: 24 Weeks
Population: Overall number of participants analyzed is the total number of responders at Week 24.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Severe depression | 0 Participants |
| Placebo | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Moderate depression | 0 Participants |
| Placebo | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | No depression | 52 Participants |
| Placebo | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Mild depression | 15 Participants |
| Placebo | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Very severe depression | 2 Participants |
| OPN-375 186 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Moderate depression | 4 Participants |
| OPN-375 186 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | No depression | 55 Participants |
| OPN-375 186 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Mild depression | 12 Participants |
| OPN-375 186 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Severe depression | 0 Participants |
| OPN-375 186 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Very severe depression | 0 Participants |
| OPN-375 372 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Very severe depression | 0 Participants |
| OPN-375 372 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Severe depression | 1 Participants |
| OPN-375 372 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | No depression | 51 Participants |
| OPN-375 372 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Moderate depression | 2 Participants |
| OPN-375 372 μg BID | Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) | Mild depression | 15 Participants |
Secondary
Time to First Acute Exacerbation of Chronic Sinusitis
Comparing the distribution of time to first acute exacerbation of chronic sinusitis across treatment groups. An exacerbation of chronic sinusitis is defined as a worsening of symptoms that requires escalation of treatment.
Time frame: 24 Weeks
Population: Full analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to First Acute Exacerbation of Chronic Sinusitis | 9.83 Weeks | Standard Error 0.215 |
| OPN-375 186 μg BID | Time to First Acute Exacerbation of Chronic Sinusitis | 5.00 Weeks | Standard Error 0 |
| OPN-375 372 μg BID | Time to First Acute Exacerbation of Chronic Sinusitis | 8.04 Weeks | Standard Error 0.131 |
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. Values provided for this outcome are the count of subjects with at least 1 AE in each category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Severe | 1 Participants |
| Placebo | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Moderate | 17 Participants |
| Placebo | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Mild | 13 Participants |
| OPN-375 186 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Moderate | 8 Participants |
| OPN-375 186 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Mild | 15 Participants |
| OPN-375 186 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Severe | 1 Participants |
| OPN-375 372 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Mild | 22 Participants |
| OPN-375 372 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Severe | 2 Participants |
| OPN-375 372 μg BID | Evaluation of Safety by Recording the Severity of Adverse Events (AEs) | Moderate | 19 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 |
|---|---|---|---|---|
| Placebo | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Systolic Blood Pressure | 126.2 mmHg | Standard Deviation 11.3 |
| Placebo | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Diastolic Blood Pressure | 78.1 mmHg | Standard Deviation 8.29 |
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Systolic Blood Pressure | 124.0 mmHg | Standard Deviation 13.26 |
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Diastolic Blood Pressure | 76.5 mmHg | Standard Deviation 7.88 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Systolic Blood Pressure | 126.9 mmHg | Standard Deviation 11.94 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Blood Pressure | Diastolic Blood Pressure | 78.5 mmHg | Standard Deviation 7.69 |
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 |
|---|---|---|---|
| Placebo | Evaluation of Safety Measuring Vital Signs- Pulse | 73.7 beats per minute | Standard Deviation 7.37 |
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Pulse | 74.1 beats per minute | Standard Deviation 6.76 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Pulse | 72.1 beats per minute | Standard Deviation 8.18 |
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 |
|---|---|---|---|
| Placebo | Evaluation of Safety Measuring Vital Signs- Weight | 77.86 kg | Standard Deviation 16.527 |
| OPN-375 186 μg BID | Evaluation of Safety Measuring Vital Signs- Weight | 76.30 kg | Standard Deviation 15.25 |
| OPN-375 372 μg BID | Evaluation of Safety Measuring Vital Signs- Weight | 81.14 kg | Standard Deviation 20.091 |
Other Pre-specified
Evaluation of Safety - Monitoring Concomitant Medication Usage
Assessment for safety from the collection of information for concomitant medications usage. Top 5 reported con-meds by therapeutic class are listed for this outcome.
Time frame: 24 Weeks
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | HMG-CoA Reductase Inhibitors | 8 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Other Nasal Preparations (includes sodium chloride and sea water) | 22 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Adrenergics in combination with corticosteroids or other drugs | 15 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Glucocorticoids | 11 Participants |
| Placebo | Evaluation of Safety - Monitoring Concomitant Medication Usage | Selective Beta-2-adrenoreceptor Agonists | 11 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Glucocorticoids | 9 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Selective Beta-2-adrenoreceptor Agonists | 4 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Other Nasal Preparations (includes sodium chloride and sea water) | 15 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | HMG-CoA Reductase Inhibitors | 7 Participants |
| OPN-375 186 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Adrenergics in combination with corticosteroids or other drugs | 9 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Selective Beta-2-adrenoreceptor Agonists | 8 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Adrenergics in combination with corticosteroids or other drugs | 19 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Glucocorticoids | 7 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | HMG-CoA Reductase Inhibitors | 9 Participants |
| OPN-375 372 μg BID | Evaluation of Safety - Monitoring Concomitant Medication Usage | Other Nasal Preparations (includes sodium chloride and sea water) | 15 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. Overall number analyzed is the total number of responders in each treatment group.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Evaluation of Safety-Nasal Examination | Epistaxis | None | 71 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Epistaxis | Present | 0 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Septal erosion/perforation | None | 70 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Septal erosion/perforation | Present | 1 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Ulceration/Erosion | None | 71 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Ulceration/Erosion | Present | 0 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Mucosal candidiasis | None | 71 Participants |
| Placebo | Evaluation of Safety-Nasal Examination | Mucosal candidiasis | Present | 0 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Septal erosion/perforation | None | 71 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Mucosal candidiasis | None | 71 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Septal erosion/perforation | Present | 0 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion | None | 71 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion | Present | 0 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | None | 70 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | Present | 1 Participants |
| OPN-375 186 μg BID | Evaluation of Safety-Nasal Examination | Mucosal candidiasis | Present | 0 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Septal erosion/perforation | None | 70 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | Present | 4 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Epistaxis | None | 68 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Septal erosion/perforation | Present | 2 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Mucosal candidiasis | None | 72 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion | Present | 0 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Ulceration/Erosion | None | 72 Participants |
| OPN-375 372 μg BID | Evaluation of Safety-Nasal Examination | Mucosal candidiasis | Present | 0 Participants |