Bilateral Nasal Polyposis
Conditions
Brief summary
The primary objective of this study is to compare the efficacy of intranasal administration of 100, 200, and 400 μg of fluticasone propionate twice a day delivered by the OptiNose device with placebo in subjects with bilateral nasal polyposis. Two co-primary endpoints will be used in the study: reduction of nasal congestion/obstruction symptoms at the end of Week 4 of the double-blind treatment phase measured by the 7 day average instantaneous AM diary symptom scores, and reduction in total polyp grade (sum of scores from both nasal cavities) over the 16 weeks of the double-blind treatment phase as determined by the Lildholdt scale score measured by nasoendoscopy.
Detailed description
This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to assess the efficacy and safety of intranasal administration of 3 doses of OPN-375 (100, 200, and 400 µg bid) in subjects with bilateral nasal polyposis and nasal congestion. This study consisted of 3 phases. After signing informed consent, subjects who met eligibility criteria at Visit 1 (screening) entered the study. 1. Pretreatment phase (single-blind, placebo, run-in): 7 to up to 14 days duration, to determine disease status eligibility and to ensure the subject was able to comply with study procedures prior to randomization and enrolment in the double-blind treatment phase. 2. Double-blind treatment phase: 16 weeks duration with 6 scheduled visits starting with Visit 2, Day 1 (baseline) when eligible subjects were randomized by balance allocation to 1 of 4 treatment groups and ending at Visit 7 (Week 16). 3. Open-label extension phase: 8 weeks duration with 1 scheduled visit (Visit 8 \[Week 24\]).
Interventions
DRUGFluticasone Propionate
Delivered via Optinose Exhalation Delivery System
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
* Men or women aged 18 years and older * Women must * 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 * be surgically sterile (have had a hysterectomy or bilateral oophorectomy, or tubal ligation at least 1 year before screening) or otherwise be incapable of pregnancy, or * be postmenopausal (spontaneous amenorrhea for at least 1 year). * Women of child-bearing potential must have a negative serum beta-human chorionic gonadotropin (B-hCG) or urine pregnancy test (depending on local regulations) at the screening visit * Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal cavities as determined by the Lildholdt scale score measured by nasoendoscopy at both screening and baseline visits * Must have at least moderate symptoms of nasal congestion/obstruction as reported by the subject for the 7 day period preceding the screening visit * At the baseline visit (Day 1), must have a morning score of at least 2 (moderate) on nasal congestion/obstruction recorded on the subject diary for at least 5 of the last 7 days of the 7 to up to 14 day run-in period * Must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization * Subjects with comorbid asthma or COPD must be stable with no exacerbations (eg, no emergency room visits, hospitalizations, or oral or parenteral steroid use) within the 3 months before the screening visit. 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 screening with plans to continue use throughout the study. * Must be able to cease treatment with intranasal medications including, but not limited to, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium bromide, inhaled corticosteroids (except permitted doses listed above for comorbid asthma and COPD) at the screening visit * Must be able to cease treatment with oral and nasal decongestants and antihistamines at the screening visit * Must be able to use the OptiNose device correctly; all subjects will be required to demonstrate correct use of the placebo device at screening, Visit 1. * 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
* Women who are pregnant or lactating * Have complete or near-complete obstruction of the nasal cavities * Inability to achieve bilateral nasal airflow for any reason including nasal septum deviation * Inability to have each nasal cavity examined for any reason including nasal septum deviation * Nasal septum perforation * Has had more than 1 episode of epistaxis with frank bleeding in the month before the screening visit * Have evidence of significant baseline mucosal injury, ulceration or erosion (eg, exposed cartilage, perforation) on baseline nasal examination/nasal endoscopy * History of more than 5 sinonasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime) * History of sinus or nasal surgery within 6 months before the screening visit * History of any surgical procedure that prevents the ability to accurately grade polyps * Have symptoms of seasonal allergic rhinitis at screening or baseline and/or, based on time of year, would anticipate onset of symptoms within 4 weeks of randomization * Current, ongoing rhinitis medicamentosa (rebound rhinitis) * Have significant oral structural abnormalities, eg, a cleft palate * Diagnosis of cystic fibrosis * History of Churg-Strauss syndrome or dyskinetic ciliary syndromes * Purulent nasal infection, acute sinusitis, or upper respiratory tract infection within 2 weeks before the screening visit. Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution Note: Subjects who are taking prophylactic antibiotics will be allowed to enter the study as long as they intend to continue the antibiotics for the duration of the study. * Planned sinonasal surgery during the period of the study * Allergy, hypersensitivity, or contraindication to corticosteroids or steroids * Allergy or hypersensitivity to any excipients in study drug * Exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral, intra-articular, or epidural steroids, high dose topical steroids) within 1 month before the screening visit; except as noted in inclusion criteria for subjects with comorbid asthma or COPD * Have nasal candidiasis * Have taken a potent CYP3A4 inhibitor within 14 days before the screening visit. * History or current diagnosis of any form of glaucoma or ocular hypertension (ie, \>21 mmHg) * History of intraocular pressure elevation on any form of steroid therapy * History or current diagnosis of the presence (in either eye) of a cataract * 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 * A recent (within 1 year of the screening visit) clinically significant history of drug or alcohol use, abuse, or dependence that, in the opinion of the investigator could interfere with the subject's participation or compliance in the study * Positive urine drug screen at screening visit for drugs of abuse, with the exception of prescribed medications for legitimate medical conditions * Have participated in an investigational drug clinical trial within 30 days of the screening visit * Employees 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, as well as family members of the employees or the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms | Baseline, Week 4 of the double-blind treatment phase | Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 4 Visit of the double-blind treatment phase |
| Change in Total Polyp Grade | Baseline, Week 16 of the double-blind treatment phase | Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. A summary of the changes from baseline to Week 16 in total polyp grade. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate Reduction in total polyp grade (sum of scores from both nasal cavities) at Week 16 of double-blind treatment phase; Included patients with nasal polyps at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Facial Pain or Pressure Score (7-day Instantaneous Morning) | Baseline, Week 16 of the double-blind treatment phase | Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase |
| Hyposmia Score (7-day Instantaneous Morning) | Baseline, Week 16 of the double-blind treatment phase | Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase |
| Sinonasal Outcome Test 22 (SNOT-22) Total Score | Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase | SNOT-22 is a subject-completed questionnaire that consists of 22 questions. The questions on the SNOT-22 efficacy evaluation were used to calculate a total score. 22 questions are divided among 4 subscales: Rhinologic (7 questions), Ear/Facial Symptoms (4 questions), Sleep Function (3 questions), and Psychological Issues (6 questions). Each item was rated on the 5-point scale. The total score can range from 0-110, 0 being the best and 110 being the worst. 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 |
| MOS Sleep-R Score | Baseline, Week 16 of the double-blind treatment phase | The MOS Sleep-R is a brief, self-administered, validated questionnaire designed to measure key aspects of sleep, such as disturbance, adequacy, somnolence, and quantity. The 12-item version with a 4-week recall was used in this study. The score range for the 12-item version is 0 to 100, lower scores indicating better sleep and higher scores indicating worse sleep. The scale yields a Sleep Problem Index and scores on the following 6 subscales: Sleep Disturbance, Snoring, Shortness of Breath or Headache, Sleep Adequacy, Sleep Somnolence, and Sleep Quantity. |
| Rhinosinusitis Disability Index (RSDI) Total Score | Baseline, Week 16 of the double-blind treatment phase | The RSDI is a subject-completed instrument that evaluates the self-perceived impact of disease specific head and neck disorders. The RSDI has 30 items in 3 domains: Physical (11 items), Functional (9 items), and Emotional (10 items). The RSDI scale ranges from 0-120, 0 being better quality of life and less impact of CRS on daily function and 120 being worse quality of life and more impact of CRS on daily function. |
| Congestion/Obstruction Scores (7-day Instantaneous Morning) | Baseline, Week 16 of the double-blind treatment phase | Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase |
| SF-36v2 - Physical Component | Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase | The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health perceptions. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability. |
| Patient Global Impression of Change (PGIC) Score | Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase | Subject responses to the question: Since starting the study drug, how would you rate the change in your symptoms? Percentage includes patients who scored either very much improved, much improved, or minimally improved. |
| Peak Nasal Inspiratory Flow (PNIF) | Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label treatment phase | The PNIF is an assessment of nasal passage obstruction and was measured using an In-Check portable nasal inspiratory flow meter. To measure PNIF, a mask was placed over the nose during inspiration and inspiratory flow was recorded. Each subject inhaled 3 times and each measurement was recorded. The PNIF value used was the greatest of the 3 results at each time point. |
| Polyp Grade of 0 in at Least One Nostril | Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase | Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. This outcome measured how many patients with a polyp grad of 0 in at least 1 nostril. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate |
| Nasal Polyp Surgery Eligilbilty | Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase | A subject was considered eligible for surgical intervention if the following conditions were met: * Subject has had moderate symptoms of congestion from nasal polyposis for ≥ 3 months. * Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for ≥ 6 weeks. * Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for ≥ 6 weeks. * Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score ≥ 2 in at least 1 nostril). |
| SF-36v2 - Mental Component | Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase | The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability. |
| Change in Rhinorrhea Score (7-day Instantaneous Morning) | Baseline, Week 16 of the double-blind treatment phase | Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks | 82 |
| OPN-375 100 μg BID OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks | 81 |
| OPN-375 200 μg BID OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks | 80 |
| OPN-375 400 μg BID OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks | 80 |
| Total | 323 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Treatment Phase (Wks 1-16) | Adverse Event | 4 | 2 | 3 | 1 |
| Double-Blind Treatment Phase (Wks 1-16) | Lack of Efficacy | 6 | 0 | 3 | 2 |
| Double-Blind Treatment Phase (Wks 1-16) | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Double-Blind Treatment Phase (Wks 1-16) | Protocol Violation | 0 | 2 | 0 | 1 |
| Double-Blind Treatment Phase (Wks 1-16) | Withdrawal by Subject | 2 | 2 | 2 | 0 |
| Open-Label Extension Phase (Wks 17-24) | Adverse Event | 0 | 2 | 1 | 0 |
| Open-Label Extension Phase (Wks 17-24) | Lack of Efficacy | 1 | 0 | 2 | 1 |
| Open-Label Extension Phase (Wks 17-24) | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | OPN-375 100 μg BID | OPN-375 200 μg BID | OPN-375 400 μg BID | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 12.7 | 44.9 years STANDARD_DEVIATION 12.7 | 46.4 years STANDARD_DEVIATION 12.7 | 43.9 years STANDARD_DEVIATION 12.6 | 45.3 years STANDARD_DEVIATION 13 |
| Facial Pain or Pressure Score (7-day instantaneous morning) | 1.57 units on a scale | 1.53 units on a scale | 1.48 units on a scale | 1.62 units on a scale | 1.65 units on a scale |
| Hyposomia Score (7-day instantaneous morning) | 2.41 units on a scale | 2.31 units on a scale | 2.49 units on a scale | 2.44 units on a scale | 2.42 units on a scale |
| Medical Outcomes Study Sleep Scale Revised (MOS Sleep-R) | 42.71 units on a scale | 37.8 units on a scale | 46.6 units on a scale | 43.7 units on a scale | 42.8 units on a scale |
| Nasal Congestion/Obstruction Score (7-Day Instantaneous Morning) | 2.27 units on a scale | 2.22 units on a scale | 2.24 units on a scale | 2.29 units on a scale | 2.31 units on a scale |
| Nasal Polyp Surgery Eligibility | 189 Participants | 45 Participants | 44 Participants | 47 Participants | 53 Participants |
| Peak Nasal Inspiratory Flow (PNIF) | 104.3 L/min | 111.6 L/min | 97.1 L/min | 103.2 L/min | 105.1 L/min |
| Previous polyp removal surgery via polypectomy only | 120 Participants | 27 Participants | 33 Participants | 27 Participants | 33 Participants |
| Previous sinus surgery for polyp removal or sinus surgery | 124 Participants | 34 Participants | 27 Participants | 30 Participants | 33 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 2 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Black/African American | 26 Participants | 3 Participants | 6 Participants | 9 Participants | 8 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 283 Participants | 74 Participants | 72 Participants | 69 Participants | 68 Participants |
| Region of Enrollment Canada | 18 Participants | 5 Participants | 5 Participants | 4 Participants | 4 Participants |
| Region of Enrollment Czechia | 56 Participants | 15 Participants | 14 Participants | 13 Participants | 14 Participants |
| Region of Enrollment South Africa | 30 Participants | 6 Participants | 8 Participants | 7 Participants | 9 Participants |
| Region of Enrollment Ukraine | 65 Participants | 17 Participants | 16 Participants | 16 Participants | 16 Participants |
| Region of Enrollment United Kingdom | 11 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 143 Participants | 36 Participants | 35 Participants | 36 Participants | 36 Participants |
| Rhinorrhea Score (7-day instantaneous morning) | 1.76 units on a scale | 1.67 units on a scale | 1.75 units on a scale | 1.83 units on a scale | 1.81 units on a scale |
| Rhinosinusitis Disability Index (RSDI) Total Score | 44.69 units on a scale | 39.8 units on a scale | 45.2 units on a scale | 45.4 units on a scale | 48.3 units on a scale |
| Sex: Female, Male Female | 161 Participants | 41 Participants | 32 Participants | 42 Participants | 46 Participants |
| Sex: Female, Male Male | 162 Participants | 40 Participants | 48 Participants | 38 Participants | 36 Participants |
| Short Form (36) Health Survey Version 2 (SF-36v2) - Mental Component | 47.6 units on a scale | 49.0 units on a scale | 46.0 units on a scale | 47.8 units on a scale | 47.6 units on a scale |
| Short Form (36) Health Survey Version 2 (SF-36v2) - Physical Component | 44 units on a scale | 44.7 units on a scale | 43.9 units on a scale | 43.9 units on a scale | 43.5 units on a scale |
| Sinonasal Outcome Test 22 (SNOT-22) Total Score | 51 units on a scale | 46.1 units on a scale | 51.8 units on a scale | 52.4 units on a scale | 53.7 units on a scale |
| Total Polyp Grading Score (sum of scores from both nasal cavities) | 3.75 Units on a Scale | 3.6 Units on a Scale | 3.9 Units on a Scale | 3.7 Units on a Scale | 3.8 Units on a Scale |
| Use of intranasal corticosteroid (ICS) treatment for polyps in past 10 years | 305 Participants | 77 Participants | 76 Participants | 75 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 81 | 0 / 80 | 0 / 79 | 0 / 282 |
| other Total, other adverse events | 42 / 82 | 40 / 81 | 45 / 80 | 50 / 79 | 38 / 282 |
| serious Total, serious adverse events | 0 / 82 | 1 / 81 | 0 / 80 | 1 / 79 | 2 / 282 |
Outcome results
Primary
Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 4 Visit of the double-blind treatment phase
Time frame: Baseline, Week 4 of the double-blind treatment phase
Population: Missing data were imputed using the multiple imputation method in the primary analyses for the co-primary efficacy variables. For other efficacy analyses, missing or invalid values were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms | -0.26 units on a scale | Standard Deviation 0.08 |
| OPN-375 100 μg BID | Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms | -0.53 units on a scale | Standard Deviation 0.08 |
| OPN-375 200 μg BID | Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms | -0.56 units on a scale | Standard Deviation 0.08 |
| OPN-375 400 μg BID | Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms | -0.67 units on a scale | Standard Deviation 0.08 |
Primary
Change in Total Polyp Grade
Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. A summary of the changes from baseline to Week 16 in total polyp grade. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate Reduction in total polyp grade (sum of scores from both nasal cavities) at Week 16 of double-blind treatment phase; Included patients with nasal polyps at baseline
Time frame: Baseline, Week 16 of the double-blind treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Total Polyp Grade | -0.57 units on a scale | Standard Deviation 0.14 |
| OPN-375 100 μg BID | Change in Total Polyp Grade | -1.04 units on a scale | Standard Deviation 0.14 |
| OPN-375 200 μg BID | Change in Total Polyp Grade | -1.14 units on a scale | Standard Deviation 0.14 |
| OPN-375 400 μg BID | Change in Total Polyp Grade | -1.14 units on a scale | Standard Deviation 0.14 |
Secondary
Change in Rhinorrhea Score (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase
Time frame: Baseline, Week 16 of the double-blind treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Rhinorrhea Score (7-day Instantaneous Morning) | -0.50 units on a scale | Standard Deviation 0.1 |
| OPN-375 100 μg BID | Change in Rhinorrhea Score (7-day Instantaneous Morning) | -0.80 units on a scale | Standard Deviation 0.1 |
| OPN-375 200 μg BID | Change in Rhinorrhea Score (7-day Instantaneous Morning) | -0.89 units on a scale | Standard Deviation 0.1 |
| OPN-375 400 μg BID | Change in Rhinorrhea Score (7-day Instantaneous Morning) | -0.92 units on a scale | Standard Deviation 0.1 |
Secondary
Congestion/Obstruction Scores (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase
Time frame: Baseline, Week 16 of the double-blind treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Congestion/Obstruction Scores (7-day Instantaneous Morning) | -0.53 units on a scale | Standard Deviation 0.11 |
| OPN-375 100 μg BID | Congestion/Obstruction Scores (7-day Instantaneous Morning) | -0.93 units on a scale | Standard Deviation 0.1 |
| OPN-375 200 μg BID | Congestion/Obstruction Scores (7-day Instantaneous Morning) | -0.99 units on a scale | Standard Deviation 0.1 |
| OPN-375 400 μg BID | Congestion/Obstruction Scores (7-day Instantaneous Morning) | -1.07 units on a scale | Standard Deviation 0.1 |
Secondary
Facial Pain or Pressure Score (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase
Time frame: Baseline, Week 16 of the double-blind treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Facial Pain or Pressure Score (7-day Instantaneous Morning) | -0.41 units on a scale | Standard Deviation 0.11 |
| OPN-375 100 μg BID | Facial Pain or Pressure Score (7-day Instantaneous Morning) | -0.65 units on a scale | Standard Deviation 0.1 |
| OPN-375 200 μg BID | Facial Pain or Pressure Score (7-day Instantaneous Morning) | -0.72 units on a scale | Standard Deviation 0.1 |
| OPN-375 400 μg BID | Facial Pain or Pressure Score (7-day Instantaneous Morning) | -0.68 units on a scale | Standard Deviation 0.1 |
Secondary
Hyposmia Score (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase
Time frame: Baseline, Week 16 of the double-blind treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Hyposmia Score (7-day Instantaneous Morning) | -0.23 units on a scale | Standard Deviation 0.12 |
| OPN-375 100 μg BID | Hyposmia Score (7-day Instantaneous Morning) | -0.45 units on a scale | Standard Deviation 0.11 |
| OPN-375 200 μg BID | Hyposmia Score (7-day Instantaneous Morning) | -0.53 units on a scale | Standard Deviation 0.11 |
| OPN-375 400 μg BID | Hyposmia Score (7-day Instantaneous Morning) | -0.60 units on a scale | Standard Deviation 0.11 |
Secondary
MOS Sleep-R Score
The MOS Sleep-R is a brief, self-administered, validated questionnaire designed to measure key aspects of sleep, such as disturbance, adequacy, somnolence, and quantity. The 12-item version with a 4-week recall was used in this study. The score range for the 12-item version is 0 to 100, lower scores indicating better sleep and higher scores indicating worse sleep. The scale yields a Sleep Problem Index and scores on the following 6 subscales: Sleep Disturbance, Snoring, Shortness of Breath or Headache, Sleep Adequacy, Sleep Somnolence, and Sleep Quantity.
Time frame: Baseline, Week 16 of the double-blind treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | MOS Sleep-R Score | -8.53 units on a scale | Standard Deviation 1.61 |
| OPN-375 100 μg BID | MOS Sleep-R Score | -10.96 units on a scale | Standard Deviation 1.59 |
| OPN-375 200 μg BID | MOS Sleep-R Score | -14.24 units on a scale | Standard Deviation 1.59 |
| OPN-375 400 μg BID | MOS Sleep-R Score | -10.66 units on a scale | Standard Deviation 1.55 |
Secondary
Nasal Polyp Surgery Eligilbilty
A subject was considered eligible for surgical intervention if the following conditions were met: * Subject has had moderate symptoms of congestion from nasal polyposis for ≥ 3 months. * Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for ≥ 6 weeks. * Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for ≥ 6 weeks. * Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score ≥ 2 in at least 1 nostril).
Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase
Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Nasal Polyp Surgery Eligilbilty | Week 16 | 27 Participants |
| Placebo | Nasal Polyp Surgery Eligilbilty | Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) | 15 Participants |
| OPN-375 100 μg BID | Nasal Polyp Surgery Eligilbilty | Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) | 14 Participants |
| OPN-375 100 μg BID | Nasal Polyp Surgery Eligilbilty | Week 16 | 17 Participants |
| OPN-375 200 μg BID | Nasal Polyp Surgery Eligilbilty | Week 16 | 21 Participants |
| OPN-375 200 μg BID | Nasal Polyp Surgery Eligilbilty | Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) | 17 Participants |
| OPN-375 400 μg BID | Nasal Polyp Surgery Eligilbilty | Week 16 | 19 Participants |
| OPN-375 400 μg BID | Nasal Polyp Surgery Eligilbilty | Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) | 16 Participants |
Secondary
Patient Global Impression of Change (PGIC) Score
Subject responses to the question: Since starting the study drug, how would you rate the change in your symptoms? Percentage includes patients who scored either very much improved, much improved, or minimally improved.
Time frame: Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Patient Global Impression of Change (PGIC) Score | Week 16 | 51 Participants |
| Placebo | Patient Global Impression of Change (PGIC) Score | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 59 Participants |
| OPN-375 100 μg BID | Patient Global Impression of Change (PGIC) Score | Week 16 | 56 Participants |
| OPN-375 100 μg BID | Patient Global Impression of Change (PGIC) Score | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 62 Participants |
| OPN-375 200 μg BID | Patient Global Impression of Change (PGIC) Score | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 62 Participants |
| OPN-375 200 μg BID | Patient Global Impression of Change (PGIC) Score | Week 16 | 62 Participants |
| OPN-375 400 μg BID | Patient Global Impression of Change (PGIC) Score | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 66 Participants |
| OPN-375 400 μg BID | Patient Global Impression of Change (PGIC) Score | Week 16 | 67 Participants |
Secondary
Peak Nasal Inspiratory Flow (PNIF)
The PNIF is an assessment of nasal passage obstruction and was measured using an In-Check portable nasal inspiratory flow meter. To measure PNIF, a mask was placed over the nose during inspiration and inspiratory flow was recorded. Each subject inhaled 3 times and each measurement was recorded. The PNIF value used was the greatest of the 3 results at each time point.
Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label treatment phase
Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Peak Nasal Inspiratory Flow (PNIF) | Week 16 | 17.26 L/min | Standard Deviation 6.15 |
| Placebo | Peak Nasal Inspiratory Flow (PNIF) | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 34.92 L/min | Standard Deviation 6.31 |
| OPN-375 100 μg BID | Peak Nasal Inspiratory Flow (PNIF) | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 41.61 L/min | Standard Deviation 6.21 |
| OPN-375 100 μg BID | Peak Nasal Inspiratory Flow (PNIF) | Week 16 | 36.57 L/min | Standard Deviation 6.06 |
| OPN-375 200 μg BID | Peak Nasal Inspiratory Flow (PNIF) | Week 16 | 35.94 L/min | Standard Deviation 6.08 |
| OPN-375 200 μg BID | Peak Nasal Inspiratory Flow (PNIF) | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 44.70 L/min | Standard Deviation 6.27 |
| OPN-375 400 μg BID | Peak Nasal Inspiratory Flow (PNIF) | Week 16 | 35.43 L/min | Standard Deviation 5.95 |
| OPN-375 400 μg BID | Peak Nasal Inspiratory Flow (PNIF) | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 35.64 L/min | Standard Deviation 6.09 |
Secondary
Polyp Grade of 0 in at Least One Nostril
Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. This outcome measured how many patients with a polyp grad of 0 in at least 1 nostril. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate
Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Polyp Grade of 0 in at Least One Nostril | Week 16 | 9 Participants |
| Placebo | Polyp Grade of 0 in at Least One Nostril | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 17 Participants |
| OPN-375 100 μg BID | Polyp Grade of 0 in at Least One Nostril | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 24 Participants |
| OPN-375 100 μg BID | Polyp Grade of 0 in at Least One Nostril | Week 16 | 19 Participants |
| OPN-375 200 μg BID | Polyp Grade of 0 in at Least One Nostril | Week 16 | 12 Participants |
| OPN-375 200 μg BID | Polyp Grade of 0 in at Least One Nostril | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 16 Participants |
| OPN-375 400 μg BID | Polyp Grade of 0 in at Least One Nostril | Week 16 | 14 Participants |
| OPN-375 400 μg BID | Polyp Grade of 0 in at Least One Nostril | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 19 Participants |
Secondary
Rhinosinusitis Disability Index (RSDI) Total Score
The RSDI is a subject-completed instrument that evaluates the self-perceived impact of disease specific head and neck disorders. The RSDI has 30 items in 3 domains: Physical (11 items), Functional (9 items), and Emotional (10 items). The RSDI scale ranges from 0-120, 0 being better quality of life and less impact of CRS on daily function and 120 being worse quality of life and more impact of CRS on daily function.
Time frame: Baseline, Week 16 of the double-blind treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rhinosinusitis Disability Index (RSDI) Total Score | -10.71 units on a scale | Standard Deviation 2.07 |
| OPN-375 100 μg BID | Rhinosinusitis Disability Index (RSDI) Total Score | -17.08 units on a scale | Standard Deviation 1.99 |
| OPN-375 200 μg BID | Rhinosinusitis Disability Index (RSDI) Total Score | -16.44 units on a scale | Standard Deviation 2.02 |
| OPN-375 400 μg BID | Rhinosinusitis Disability Index (RSDI) Total Score | -16.37 units on a scale | Standard Deviation 1.94 |
Secondary
SF-36v2 - Mental Component
The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | SF-36v2 - Mental Component | Week 16 | 0.70 units on a scale | Standard Deviation 0.87 |
| Placebo | SF-36v2 - Mental Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 4.44 units on a scale | Standard Deviation 0.83 |
| OPN-375 100 μg BID | SF-36v2 - Mental Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 3.37 units on a scale | Standard Deviation 0.8 |
| OPN-375 100 μg BID | SF-36v2 - Mental Component | Week 16 | 3.19 units on a scale | Standard Deviation 0.84 |
| OPN-375 200 μg BID | SF-36v2 - Mental Component | Week 16 | 4.03 units on a scale | Standard Deviation 0.85 |
| OPN-375 200 μg BID | SF-36v2 - Mental Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 5.82 units on a scale | Standard Deviation 0.84 |
| OPN-375 400 μg BID | SF-36v2 - Mental Component | Week 16 | 1.83 units on a scale | Standard Deviation 0.82 |
| OPN-375 400 μg BID | SF-36v2 - Mental Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 3.61 units on a scale | Standard Deviation 0.78 |
Secondary
SF-36v2 - Physical Component
The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health perceptions. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | SF-36v2 - Physical Component | Week 16 | 2.67 units on a scale | Standard Deviation 0.76 |
| Placebo | SF-36v2 - Physical Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 6.97 units on a scale | Standard Deviation 0.78 |
| OPN-375 100 μg BID | SF-36v2 - Physical Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 6.55 units on a scale | Standard Deviation 0.75 |
| OPN-375 100 μg BID | SF-36v2 - Physical Component | Week 16 | 4.12 units on a scale | Standard Deviation 0.74 |
| OPN-375 200 μg BID | SF-36v2 - Physical Component | Week 16 | 5.19 units on a scale | Standard Deviation 0.74 |
| OPN-375 200 μg BID | SF-36v2 - Physical Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 7.18 units on a scale | Standard Deviation 0.78 |
| OPN-375 400 μg BID | SF-36v2 - Physical Component | Week 16 | 3.58 units on a scale | Standard Deviation 0.72 |
| OPN-375 400 μg BID | SF-36v2 - Physical Component | Week 24 (all pts on 400 μg OPN-375 BID wks 17-24) | 4.90 units on a scale | Standard Deviation 0.73 |
Secondary
Sinonasal Outcome Test 22 (SNOT-22) Total Score
SNOT-22 is a subject-completed questionnaire that consists of 22 questions. The questions on the SNOT-22 efficacy evaluation were used to calculate a total score. 22 questions are divided among 4 subscales: Rhinologic (7 questions), Ear/Facial Symptoms (4 questions), Sleep Function (3 questions), and Psychological Issues (6 questions). Each item was rated on the 5-point scale. The total score can range from 0-110, 0 being the best and 110 being the worst. 0: No problem 1. Very mild problem 2. Mild or slight problem 3. Moderate problem 4. Severe problem 5. Problem as bad as it can be
Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 16 | -10.96 units on a scale | Standard Deviation 2.07 |
| Placebo | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 24 (all pts on 400 μg | -20.78 units on a scale | Standard Deviation 2.1 |
| OPN-375 100 μg BID | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 24 (all pts on 400 μg | -21.20 units on a scale | Standard Deviation 2.07 |
| OPN-375 100 μg BID | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 16 | -18.32 units on a scale | Standard Deviation 2.05 |
| OPN-375 200 μg BID | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 16 | -19.56 units on a scale | Standard Deviation 2.04 |
| OPN-375 200 μg BID | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 24 (all pts on 400 μg | -23.28 units on a scale | Standard Deviation 2.08 |
| OPN-375 400 μg BID | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 16 | -19.80 units on a scale | Standard Deviation 2.05 |
| OPN-375 400 μg BID | Sinonasal Outcome Test 22 (SNOT-22) Total Score | Change from baseline to Week 24 (all pts on 400 μg | -21.72 units on a scale | Standard Deviation 2.07 |