Trial Outcomes & Findings for Study Evaluating the Efficacy and Safety of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Twice a Day (BID) Using a Novel Bi Directional Device in Subjects With Bilateral Nasal Polyposis Followed by an 8-Week Open-Label Extension Phase to Assess Safety (NCT NCT01622569)

NCT ID: NCT01622569

Last Updated: 2018-12-26

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 323 participants
• Primary outcome timeframe: Baseline, Week 4 of the double-blind treatment phase
• Results posted on: 2018-12-26

Participant Flow

Participant milestones

Measure	Placebo Matching placebo BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks	100 μg OPN-375 OPN-375 100 μg BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks	200 μg OPN-375 OPN-375 200 μg BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks	400 μg EDS-FLU OPN-375 400 μg BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks
Double-Blind Treatment Phase (Wks 1-16) STARTED	82	81	80	80
Double-Blind Treatment Phase (Wks 1-16) COMPLETED	70	75	71	76
Double-Blind Treatment Phase (Wks 1-16) NOT COMPLETED	12	6	9	4
Open-Label Extension Phase (Wks 17-24) STARTED	68	72	67	75
Open-Label Extension Phase (Wks 17-24) COMPLETED	67	70	64	73
Open-Label Extension Phase (Wks 17-24) NOT COMPLETED	1	2	3	2

Reasons for withdrawal

Measure	Placebo Matching placebo BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks	100 μg OPN-375 OPN-375 100 μg BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks	200 μg OPN-375 OPN-375 200 μg BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks	400 μg EDS-FLU OPN-375 400 μg BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks
Double-Blind Treatment Phase (Wks 1-16) Adverse Event	4	2	3	1
Double-Blind Treatment Phase (Wks 1-16) Lost to Follow-up	0	0	1	0
Double-Blind Treatment Phase (Wks 1-16) Lack of Efficacy	6	0	3	2
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

These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms. Included patients with nasal polyps at baseline

Baseline characteristics by cohort

Measure	Placebo n=82 Participants Matching Placebo BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=81 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=80 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=80 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	Total n=323 Participants Total of all reporting groups
Age, Continuous	45.3 years STANDARD_DEVIATION 13.0 • n=82 Participants	44.9 years STANDARD_DEVIATION 12.7 • n=81 Participants	46.4 years STANDARD_DEVIATION 12.7 • n=80 Participants	43.9 years STANDARD_DEVIATION 12.6 • n=80 Participants	45.1 years STANDARD_DEVIATION 12.7 • n=323 Participants
Sex: Female, Male Female	46 Participants n=82 Participants	41 Participants n=81 Participants	32 Participants n=80 Participants	42 Participants n=80 Participants	161 Participants n=323 Participants
Sex: Female, Male Male	36 Participants n=82 Participants	40 Participants n=81 Participants	48 Participants n=80 Participants	38 Participants n=80 Participants	162 Participants n=323 Participants
Race/Ethnicity, Customized White	68 Participants n=82 Participants	74 Participants n=81 Participants	72 Participants n=80 Participants	69 Participants n=80 Participants	283 Participants n=323 Participants
Race/Ethnicity, Customized Black/African American	8 Participants n=82 Participants	3 Participants n=81 Participants	6 Participants n=80 Participants	9 Participants n=80 Participants	26 Participants n=323 Participants
Race/Ethnicity, Customized Asian	5 Participants n=82 Participants	2 Participants n=81 Participants	2 Participants n=80 Participants	0 Participants n=80 Participants	9 Participants n=323 Participants
Race/Ethnicity, Customized Other	1 Participants n=82 Participants	2 Participants n=81 Participants	0 Participants n=80 Participants	2 Participants n=80 Participants	5 Participants n=323 Participants
Region of Enrollment Canada	4 Participants n=82 Participants	5 Participants n=81 Participants	5 Participants n=80 Participants	4 Participants n=80 Participants	18 Participants n=323 Participants
Region of Enrollment Czechia	14 Participants n=82 Participants	15 Participants n=81 Participants	14 Participants n=80 Participants	13 Participants n=80 Participants	56 Participants n=323 Participants
Region of Enrollment United Kingdom	3 Participants n=82 Participants	2 Participants n=81 Participants	2 Participants n=80 Participants	4 Participants n=80 Participants	11 Participants n=323 Participants
Region of Enrollment Ukraine	16 Participants n=82 Participants	17 Participants n=81 Participants	16 Participants n=80 Participants	16 Participants n=80 Participants	65 Participants n=323 Participants
Region of Enrollment United States	36 Participants n=82 Participants	36 Participants n=81 Participants	35 Participants n=80 Participants	36 Participants n=80 Participants	143 Participants n=323 Participants
Region of Enrollment South Africa	9 Participants n=82 Participants	6 Participants n=81 Participants	8 Participants n=80 Participants	7 Participants n=80 Participants	30 Participants n=323 Participants
Total Polyp Grading Score (sum of scores from both nasal cavities)	3.8 Units on a Scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms. Included patients with nasal polyps at baseline	3.6 Units on a Scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms. Included patients with nasal polyps at baseline	3.9 Units on a Scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms. Included patients with nasal polyps at baseline	3.7 Units on a Scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms. Included patients with nasal polyps at baseline	3.75 Units on a Scale n=322 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms. Included patients with nasal polyps at baseline
Use of intranasal corticosteroid (ICS) treatment for polyps in past 10 years	77 Participants n=82 Participants	77 Participants n=81 Participants	76 Participants n=80 Participants	75 Participants n=80 Participants	305 Participants n=323 Participants
Previous sinus surgery for polyp removal or sinus surgery	33 Participants n=82 Participants	34 Participants n=81 Participants	27 Participants n=80 Participants	30 Participants n=80 Participants	124 Participants n=323 Participants
Previous polyp removal surgery via polypectomy only	33 Participants n=82 Participants	27 Participants n=81 Participants	33 Participants n=80 Participants	27 Participants n=80 Participants	120 Participants n=323 Participants
Nasal Congestion/Obstruction Score (7-Day Instantaneous Morning)	2.31 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.22 units on a scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.24 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.29 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.27 units on a scale n=322 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Rhinorrhea Score (7-day instantaneous morning)	1.81 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.67 units on a scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.75 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.83 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.76 units on a scale n=322 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Facial Pain or Pressure Score (7-day instantaneous morning)	1.65 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.53 units on a scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.48 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.62 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	1.57 units on a scale n=322 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Hyposomia Score (7-day instantaneous morning)	2.42 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, an who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.31 units on a scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, an who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.49 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, an who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.44 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, an who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	2.41 units on a scale n=322 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, an who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Sinonasal Outcome Test 22 (SNOT-22) Total Score	53.7 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	46.1 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	51.8 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	52.4 units on a scale n=77 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	51 units on a scale n=319 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Medical Outcomes Study Sleep Scale Revised (MOS Sleep-R)	42.8 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	37.8 units on a scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	46.6 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	43.7 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	42.71 units on a scale n=322 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Rhinosinusitis Disability Index (RSDI) Total Score	48.3 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	39.8 units on a scale n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	45.2 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	45.4 units on a scale n=78 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	44.69 units on a scale n=319 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Short Form (36) Health Survey Version 2 (SF-36v2) - Mental Component	47.6 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	49.0 units on a scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	46.0 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	47.8 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	47.6 units on a scale n=321 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Short Form (36) Health Survey Version 2 (SF-36v2) - Physical Component	43.5 units on a scale n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	44.7 units on a scale n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	43.9 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	43.9 units on a scale n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	44 units on a scale n=321 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Peak Nasal Inspiratory Flow (PNIF)	105.1 L/min n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	111.6 L/min n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	97.1 L/min n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	103.2 L/min n=79 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	104.3 L/min n=321 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.
Nasal Polyp Surgery Eligibility	53 Participants n=82 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	45 Participants n=81 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	44 Participants n=80 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	47 Participants n=78 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.	189 Participants n=321 Participants • These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=77 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=78 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=79 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=78 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms	-0.26 units on a scale Standard Deviation 0.08	-0.53 units on a scale Standard Deviation 0.08	-0.56 units on a scale Standard Deviation 0.08	-0.67 units on a scale Standard Deviation 0.08

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Placebo n=68 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=75 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=68 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=75 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Change in Total Polyp Grade	-0.57 units on a scale Standard Deviation 0.14	-1.04 units on a scale Standard Deviation 0.14	-1.14 units on a scale Standard Deviation 0.14	-1.14 units on a scale Standard Deviation 0.14

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Placebo n=82 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=81 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=80 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=79 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Congestion/Obstruction Scores (7-day Instantaneous Morning)	-0.53 units on a scale Standard Deviation 0.11	-0.93 units on a scale Standard Deviation 0.10	-0.99 units on a scale Standard Deviation 0.10	-1.07 units on a scale Standard Deviation 0.10

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Placebo n=82 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=81 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=80 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=79 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Change in Rhinorrhea Score (7-day Instantaneous Morning)	-0.50 units on a scale Standard Deviation 0.10	-0.80 units on a scale Standard Deviation 0.10	-0.89 units on a scale Standard Deviation 0.10	-0.92 units on a scale Standard Deviation 0.10

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Placebo n=82 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=81 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=80 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=79 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Facial Pain or Pressure Score (7-day Instantaneous Morning)	-0.41 units on a scale Standard Deviation 0.11	-0.65 units on a scale Standard Deviation 0.10	-0.72 units on a scale Standard Deviation 0.10	-0.68 units on a scale Standard Deviation 0.10

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Placebo n=82 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=81 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=80 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=79 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Hyposmia Score (7-day Instantaneous Morning)	-0.23 units on a scale Standard Deviation 0.12	-0.45 units on a scale Standard Deviation 0.11	-0.53 units on a scale Standard Deviation 0.11	-0.60 units on a scale Standard Deviation 0.11

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=82 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=80 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=80 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=77 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Sinonasal Outcome Test 22 (SNOT-22) Total Score Change from baseline to Week 16	-10.96 units on a scale Standard Deviation 2.07	-18.32 units on a scale Standard Deviation 2.05	-19.56 units on a scale Standard Deviation 2.04	-19.80 units on a scale Standard Deviation 2.05
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 2.10	-21.20 units on a scale Standard Deviation 2.07	-23.28 units on a scale Standard Deviation 2.08	-21.72 units on a scale Standard Deviation 2.07

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=82 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=81 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=80 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=79 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
MOS Sleep-R Score	-8.53 units on a scale Standard Deviation 1.61	-10.96 units on a scale Standard Deviation 1.59	-14.24 units on a scale Standard Deviation 1.59	-10.66 units on a scale Standard Deviation 1.55

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=67 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=71 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=69 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=73 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Rhinosinusitis Disability Index (RSDI) Total Score	-10.71 units on a scale Standard Deviation 2.07	-17.08 units on a scale Standard Deviation 1.99	-16.44 units on a scale Standard Deviation 2.02	-16.37 units on a scale Standard Deviation 1.94

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=68 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=74 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=70 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=75 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
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	3.37 units on a scale Standard Deviation 0.80	5.82 units on a scale Standard Deviation 0.84	3.61 units on a scale Standard Deviation 0.78
SF-36v2 - Mental Component Week 16	0.70 units on a scale Standard Deviation 0.87	3.19 units on a scale Standard Deviation 0.84	4.03 units on a scale Standard Deviation 0.85	1.83 units on a scale Standard Deviation 0.82

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=68 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=74 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=70 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=75 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
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	6.55 units on a scale Standard Deviation 0.75	7.18 units on a scale Standard Deviation 0.78	4.90 units on a scale Standard Deviation 0.73
SF-36v2 - Physical Component Week 16	2.67 units on a scale Standard Deviation 0.76	4.12 units on a scale Standard Deviation 0.74	5.19 units on a scale Standard Deviation 0.74	3.58 units on a scale Standard Deviation 0.72

SECONDARY outcome

Timeframe: 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."

Outcome measures

Measure	Placebo n=68 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=73 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=70 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=75 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Patient Global Impression of Change (PGIC) Score Week 16	51 Participants	56 Participants	62 Participants	67 Participants
Patient Global Impression of Change (PGIC) Score Week 24 (all pts on 400 μg OPN-375 BID wks 17-24)	59 Participants	62 Participants	62 Participants	66 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=68 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=75 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=70 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=74 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Peak Nasal Inspiratory Flow (PNIF) Week 16	17.26 L/min Standard Deviation 6.15	36.57 L/min Standard Deviation 6.06	35.94 L/min Standard Deviation 6.08	35.43 L/min Standard Deviation 5.95
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	41.61 L/min Standard Deviation 6.21	44.70 L/min Standard Deviation 6.27	35.64 L/min Standard Deviation 6.09

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=68 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=75 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=68 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=75 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Polyp Grade of 0 in at Least One Nostril Week 16	9 Participants	19 Participants	12 Participants	14 Participants
Polyp Grade of 0 in at Least One Nostril Week 24 (all pts on 400 μg OPN-375 BID wks 17-24)	17 Participants	24 Participants	16 Participants	19 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Placebo n=68 Participants Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 100 μg BID n=74 Participants OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 200 μg BID n=69 Participants OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks	OPN-375 400 μg BID n=75 Participants OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks
Nasal Polyp Surgery Eligilbilty Week 16	27 Participants	17 Participants	21 Participants	19 Participants
Nasal Polyp Surgery Eligilbilty Week 24 (all pts on OPN-375 400 mcg BID wks 17-24)	15 Participants	14 Participants	17 Participants	16 Participants

Adverse Events

Placebo (Double-Blind Phase)

Serious events: 0 serious events

Other events: 42 other events

Deaths: 0 deaths

OPN-375 100 μg BID (Double-Blind Phase)

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

OPN-375 200 μg BID (Double-Blind Phase)

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

OPN-375 400 μg BID (Double-Blind Phase)

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

OPN-375 400 μg (Open-Label Phase)

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo (Double-Blind Phase) n=82 participants at risk 100 μg BID or 200 μg BID or 400 μg Matching Placebo BID x 16 weeks	OPN-375 100 μg BID (Double-Blind Phase) n=81 participants at risk OPN-375 100 μg BID x 16 weeks	OPN-375 200 μg BID (Double-Blind Phase) n=80 participants at risk OPN-375 200 μg BID x 16 weeks	OPN-375 400 μg BID (Double-Blind Phase) n=79 participants at risk OPN-375 400 μg BID x 16 weeks	OPN-375 400 μg (Open-Label Phase) n=282 participants at risk OPN-375 400 μg BID x 8 weeks
Respiratory, thoracic and mediastinal disorders Nasal Polyps	0.00% 0/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.2% 1/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Reproductive system and breast disorders Menorrhagia	0.00% 0/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.3% 1/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Pneumonia	0.00% 0/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.

Other adverse events

Measure	Placebo (Double-Blind Phase) n=82 participants at risk 100 μg BID or 200 μg BID or 400 μg Matching Placebo BID x 16 weeks	OPN-375 100 μg BID (Double-Blind Phase) n=81 participants at risk OPN-375 100 μg BID x 16 weeks	OPN-375 200 μg BID (Double-Blind Phase) n=80 participants at risk OPN-375 200 μg BID x 16 weeks	OPN-375 400 μg BID (Double-Blind Phase) n=79 participants at risk OPN-375 400 μg BID x 16 weeks	OPN-375 400 μg (Open-Label Phase) n=282 participants at risk OPN-375 400 μg BID x 8 weeks
Ear and labyrinth disorders Ear Pain	1.2% 1/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Eye disorders Cataract Nuclear	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.2% 1/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Gastrointestinal disorders Vomiting	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Acute Sinusitis	4.9% 4/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	6.2% 5/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	7.5% 6/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	10.1% 8/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.1% 3/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Upper Respiratory Tract Infection	8.5% 7/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.2% 1/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	5.0% 4/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	6.3% 5/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.71% 2/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Nasopharyngitis	4.9% 4/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.7% 3/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	5.1% 4/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.1% 3/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Bronchitis	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.8% 3/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Influenza	3.7% 3/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Pharyngitis	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.2% 1/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.8% 3/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Otitis Media	1.2% 1/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.3% 1/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Infections and infestations Urinary Tract Infection	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Investigations Weight Increased	0.00% 0/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Investigations Intraocular Pressure Increased	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.2% 1/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Nervous system disorders Headache	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.71% 2/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Epistaxis (Spontaneously Reported by Subject)	3.7% 3/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.7% 3/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	8.8% 7/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	7.6% 6/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	4.3% 12/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Nasal Mucosal Disorder	6.1% 5/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	13.6% 11/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	7.5% 6/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	7.6% 6/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Nasal Septal Ulceration	1.2% 1/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	6.2% 5/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	6.2% 5/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	5.1% 4/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.8% 5/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	4.9% 4/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.7% 3/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	7.6% 6/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Nasal Septum Disorder	1.2% 1/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.7% 3/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.8% 3/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Asthma	6.1% 5/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.2% 1/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	3.8% 3/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.35% 1/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	2.4% 2/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	2.5% 2/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	3.7% 3/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	0.00% 0/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Epistaxis (Found on Nasoendoscopy)	3.7% 3/82 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	9.9% 8/81 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	11.2% 9/80 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	16.5% 13/79 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.	1.4% 4/282 The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.

Additional Information

Vice President Global Clinical Operations & Outsourcing

OptiNose

Phone: 267-364-3508

Email: jennifer.carothers@optinose.com

Results disclosure agreements

• Principal investigator is a sponsor employee Disclosure agreement is described in CTA between sponsor and PI
• Publication restrictions are in place

Restriction type: OTHER