Trial Outcomes & Findings for Efficacy and Safety Study of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Using a Novel Bi-directional Device (NCT NCT01624662)
NCT ID: NCT01624662
Last Updated: 2018-12-05
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 During the single-blind run-in phase and during the 16-week, double-blind treatment phase, an electronic diary was provided to each subject. Subjects reported both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptoms severity over the previous 12 hours) scores for nasal congestion/obstruction symptoms.
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
2018-12-05
Participant Flow
Participant milestones
| Measure |
Placebo
Matched placebo BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
OPN-375 100 mcg
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
OPN-375 200 mcg
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
OPN-375 400 mcg
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
|---|---|---|---|---|
|
Double-Blind Treatment Phase (Wks 1-16)
STARTED
|
80
|
81
|
80
|
82
|
|
Double-Blind Treatment Phase (Wks 1-16)
COMPLETED
|
70
|
78
|
76
|
82
|
|
Double-Blind Treatment Phase (Wks 1-16)
NOT COMPLETED
|
10
|
3
|
4
|
0
|
|
Open-Label Extension Phase (Wks 17-24)
STARTED
|
70
|
78
|
72
|
79
|
|
Open-Label Extension Phase (Wks 17-24)
COMPLETED
|
69
|
76
|
71
|
78
|
|
Open-Label Extension Phase (Wks 17-24)
NOT COMPLETED
|
1
|
2
|
1
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Matched placebo BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
OPN-375 100 mcg
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
OPN-375 200 mcg
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
OPN-375 400 mcg
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg BID (open-label) x 8 weeks
|
|---|---|---|---|---|
|
Double-Blind Treatment Phase (Wks 1-16)
Adverse Event
|
2
|
1
|
1
|
0
|
|
Double-Blind Treatment Phase (Wks 1-16)
Lack of Efficacy
|
5
|
1
|
0
|
0
|
|
Double-Blind Treatment Phase (Wks 1-16)
Protocol Violation
|
0
|
1
|
0
|
0
|
|
Double-Blind Treatment Phase (Wks 1-16)
Withdrawal by Subject
|
3
|
0
|
3
|
0
|
|
Open-Label Extension Phase (Wks 17-24)
Adverse Event
|
1
|
1
|
0
|
1
|
|
Open-Label Extension Phase (Wks 17-24)
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Open-Label Extension Phase (Wks 17-24)
Lack of Efficacy
|
0
|
0
|
1
|
0
|
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.
Baseline characteristics by cohort
| Measure |
Placebo
n=80 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg BID x 8 weeks
|
OPN-375 100 mcg
n=81 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg BID x 8 weeks
|
OPN-375 200 mcg
n=80 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg BID x 8 weeks
|
OPN-375 400 mcg
n=82 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg BID x 8 weeks
|
Total
n=323 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Rhinorrhea Score (7-day instantaneous morning)
|
1.8 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.
|
1.89 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.
|
1.86 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.
|
1.77 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.
|
1.83 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.
|
|
Facial Pain or Pressure Score (7-day instantaneous morning)
|
1.46 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.
|
1.46 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.
|
1.48 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.
|
1.35 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.
|
1.44 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.
|
|
Age, Continuous
|
46.7 years
STANDARD_DEVIATION 11.95 • n=80 Participants
|
46.7 years
STANDARD_DEVIATION 13.72 • n=81 Participants
|
44.8 years
STANDARD_DEVIATION 12.87 • n=80 Participants
|
45.0 years
STANDARD_DEVIATION 12.14 • n=82 Participants
|
45.8 years
STANDARD_DEVIATION 12.66 • n=323 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=80 Participants
|
39 Participants
n=81 Participants
|
34 Participants
n=80 Participants
|
26 Participants
n=82 Participants
|
137 Participants
n=323 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=80 Participants
|
42 Participants
n=81 Participants
|
46 Participants
n=80 Participants
|
56 Participants
n=82 Participants
|
186 Participants
n=323 Participants
|
|
Race/Ethnicity, Customized
White
|
76 Participants
n=80 Participants
|
76 Participants
n=81 Participants
|
76 Participants
n=80 Participants
|
76 Participants
n=82 Participants
|
304 Participants
n=323 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=80 Participants
|
3 Participants
n=81 Participants
|
3 Participants
n=80 Participants
|
4 Participants
n=82 Participants
|
13 Participants
n=323 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=80 Participants
|
0 Participants
n=81 Participants
|
0 Participants
n=80 Participants
|
0 Participants
n=82 Participants
|
0 Participants
n=323 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=80 Participants
|
2 Participants
n=81 Participants
|
1 Participants
n=80 Participants
|
2 Participants
n=82 Participants
|
6 Participants
n=323 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=80 Participants
|
10 participants
n=81 Participants
|
10 participants
n=80 Participants
|
9 participants
n=82 Participants
|
39 participants
n=323 Participants
|
|
Region of Enrollment
Poland
|
31 participants
n=80 Participants
|
34 participants
n=81 Participants
|
33 participants
n=80 Participants
|
33 participants
n=82 Participants
|
131 participants
n=323 Participants
|
|
Region of Enrollment
Romania
|
15 participants
n=80 Participants
|
13 participants
n=81 Participants
|
13 participants
n=80 Participants
|
14 participants
n=82 Participants
|
55 participants
n=323 Participants
|
|
Region of Enrollment
Ukraine
|
12 participants
n=80 Participants
|
14 participants
n=81 Participants
|
13 participants
n=80 Participants
|
15 participants
n=82 Participants
|
54 participants
n=323 Participants
|
|
Region of Enrollment
South Africa
|
12 participants
n=80 Participants
|
10 participants
n=81 Participants
|
11 participants
n=80 Participants
|
11 participants
n=82 Participants
|
44 participants
n=323 Participants
|
|
Total Polyp Grading Score (sum of scores from both nasal cavities)
|
3.8 units on a scale
STANDARD_DEVIATION 1.08 • 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.
|
3.8 units on a scale
STANDARD_DEVIATION 0.98 • 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.
|
3.9 units on a scale
STANDARD_DEVIATION 1.05 • 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.
|
3.9 units on a scale
STANDARD_DEVIATION 0.98 • 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.
|
3.8 units on a scale
STANDARD_DEVIATION 1.02 • 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.
|
|
Use of ICS treatment for polyps in past 10 years
|
73 Participants
n=80 Participants
|
67 Participants
n=81 Participants
|
70 Participants
n=80 Participants
|
70 Participants
n=82 Participants
|
280 Participants
n=323 Participants
|
|
Previous sinus surgery for polyp removal or sinus surgery
|
24 Participants
n=80 Participants
|
28 Participants
n=81 Participants
|
33 Participants
n=80 Participants
|
26 Participants
n=82 Participants
|
111 Participants
n=323 Participants
|
|
Previous polyp removal surgery via polypectomy only
|
30 Participants
n=80 Participants
|
33 Participants
n=81 Participants
|
25 Participants
n=80 Participants
|
27 Participants
n=82 Participants
|
115 Participants
n=323 Participants
|
|
Nasal Congestion/obstruction Score (7-day instantaneous morning)
|
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.
|
2.23 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.
|
2.20 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.
|
2.25 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.
|
2.24 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.
|
|
Hyposmia Score (7-day instantaneous morning)
|
2.47 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.
|
2.36 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.
|
2.54 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.
|
2.33 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.
|
2.43 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.
|
|
Sinonasal Outcome Test 22 (SNOT-22) Total Score
|
52.0 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.
|
48.5 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.
|
48.1 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.
|
47.1 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.
|
48.9 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.
|
|
Medical Outcomes Study Sleep Scale Revised (MOS Sleep-R)
|
41.7 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.
|
40.9 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.
|
43.0 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.
|
39.1 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.
|
41.2 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.
|
|
Rhinosinusitis Disability Index (RSDI) Total Score
|
44.9 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=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.
|
39.7 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.
|
41.5 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.
|
42.5 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) - Mental Component
|
43.1 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.
|
44.4 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.
|
45.9 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.
|
47.0 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.
|
45.1 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
|
45.8 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.
|
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.
|
46.5 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.
|
46.4 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.
|
46.2 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)
|
119.7 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.
|
123.4 L/min
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.
|
107.6 L/min
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.
|
122.7 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.
|
118.4 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
|
45 Participants
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.
|
40 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.
|
42 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.
|
45 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.
|
172 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 phasePopulation: The Full Analysis Set includes 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.
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 During the single-blind run-in phase and during the 16-week, double-blind treatment phase, an electronic diary was provided to each subject. Subjects reported both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptoms severity over the previous 12 hours) scores for nasal congestion/obstruction symptoms.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=80 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=80 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=82 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms
|
-0.24 units on a scale
Standard Error 0.07
|
-0.59 units on a scale
Standard Error 0.07
|
-0.68 units on a scale
Standard Error 0.07
|
-0.62 units on a scale
Standard Error 0.07
|
PRIMARY outcome
Timeframe: Baseline, Week 16 of the double-blind treatment phasePopulation: The Full Analysis Set includes 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.
Determined by a nasal polyp grading scale score (sum of scores from both nasal cavities) measured by nasoendoscopy
Outcome measures
| Measure |
Placebo
n=79 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=80 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=80 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=82 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Change in Total Polyp Grade
|
-0.61 units on a scale
Standard Error 0.11
|
-1.31 units on a scale
Standard Error 0.11
|
-1.22 units on a scale
Standard Error 0.11
|
-1.41 units on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Week 16 of the double-blind treatment phasePopulation: The Full Analysis Set includes 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.
Measured by the 7-day average instantaneous morning diary symptom scores
Outcome measures
| Measure |
Placebo
n=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=76 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=69 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=77 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Nasal Congestion/Obstruction Score (7-day Instantaneous Morning)
|
-0.48 units on a scale
Standard Error 0.09
|
-0.99 units on a scale
Standard Error 0.09
|
-0.93 units on a scale
Standard Error 0.09
|
-0.97 units on a scale
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Baseline, Week 16 of the double-blind treatment phasePopulation: 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.
Change from baseline in rhinorrhea symptoms, as measured by AM and PM diary symptom scores
Outcome measures
| Measure |
Placebo
n=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=76 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=69 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=77 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Change in Rhinorrhea Score (7-day Instantaneous Morning)
|
-0.42 units on a scale
Standard Error 0.09
|
-1.00 units on a scale
Standard Error 0.09
|
-0.84 units on a scale
Standard Error 0.09
|
-0.84 units on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Week 16 of the double-blind treatment phaseChange from baseline in facial pain/pressure symptoms, as measured by AM and PM diary symptom scores
Outcome measures
| Measure |
Placebo
n=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=76 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=69 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=77 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Facial Pain or Pressure Score (7-day Instantaneous Morning)
|
-0.48 units on a scale
Standard Error 0.09
|
-0.85 units on a scale
Standard Error 0.09
|
-0.81 units on a scale
Standard Error 0.09
|
-0.75 units on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Week 16 of the double-blind treatment phaseChange from baseline in hyposmia symptoms, as measured by AM and PM diary symptom scores
Outcome measures
| Measure |
Placebo
n=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=76 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=69 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=77 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Hyposmia Score (7-day Instantaneous Morning)
|
-0.24 units on a scale
Standard Error 0.10
|
-0.54 units on a scale
Standard Error 0.09
|
-0.47 units on a scale
Standard Error 0.10
|
-0.63 units on a scale
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Baseline, Week 24 of the open-label extension phasePopulation: The Full Analysis Set includes 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.
Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 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 Determined by a nasal polyp grading scale score (sum of scores from both nasal cavities measured by nasoendoscopy)
Outcome measures
| Measure |
Placebo
n=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=76 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=69 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=78 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Change in Total Nasal Polyp Score
|
-1.06 units on a scale
Standard Error 0.12
|
-1.60 units on a scale
Standard Error 0.11
|
-1.48 units on a scale
Standard Error 0.12
|
-1.75 units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phasePopulation: 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.
Subjects with a Polyp Grade of 0 (None) 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
Outcome measures
| Measure |
Placebo
n=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=79 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=73 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Polyp Grade of 0 in at Least One Nostril
Week 24 (all pts on OPN-375 400 μg BID wks 17-24)
|
6 Participants
|
19 Participants
|
17 Participants
|
22 Participants
|
|
Polyp Grade of 0 in at Least One Nostril
Week 16
|
3 Participants
|
10 Participants
|
6 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phasePopulation: 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=68 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=79 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=74 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Sinonasal Outcome Test 22 (SNOT-22) Total Score
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24)
|
-19.45 units on a scale
Standard Error 1.85
|
-22.89 units on a scale
Standard Error 1.75
|
-22.92 units on a scale
Standard Error 1.80
|
-23.21 units on a scale
Standard Error 1.72
|
|
Sinonasal Outcome Test 22 (SNOT-22) Total Score
Week 16
|
-11.70 units on a scale
Standard Error 1.81
|
-21.14 units on a scale
Standard Error 1.71
|
-21.43 units on a scale
Standard Error 1.75
|
-21.05 units on a scale
Standard Error 1.68
|
SECONDARY outcome
Timeframe: Baseline, Week 16 of the double-blind treatment phaseThe 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=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=79 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=74 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
MOS Sleep-R Score
|
-10.03 units on a scale
Standard Error 1.52
|
-14.26 units on a scale
Standard Error 1.46
|
-15.78 units on a scale
Standard Error 1.50
|
-14.30 units on a scale
Standard Error 1.44
|
SECONDARY outcome
Timeframe: Baseline, Week 16 of the double-blind treatment phaseThe 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=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=76 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=74 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Rhinosinusitis Disability Index (RSDI) Total Score
|
-7.80 units on a scale
Standard Error 1.97
|
-15.54 units on a scale
Standard Error 1.86
|
-15.37 units on a scale
Standard Error 1.89
|
-16.69 units on a scale
Standard Error 1.80
|
SECONDARY outcome
Timeframe: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phasePopulation: 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=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=77 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=74 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
SF-36v2 - Mental Component
Week 16
|
1.69 units on a scale
Standard Error 0.86
|
4.37 units on a scale
Standard Error 0.81
|
3.88 units on a scale
Standard Error 0.83
|
3.98 units on a scale
Standard Error 0.80
|
|
SF-36v2 - Mental Component
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24)
|
4.90 units on a scale
Standard Error 0.93
|
4.07 units on a scale
Standard Error 0.89
|
4.41 units on a scale
Standard Error 0.92
|
5.86 units on a scale
Standard Error 0.87
|
SECONDARY outcome
Timeframe: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phasePopulation: 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=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=77 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=74 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
SF-36v2 - Physical Component
Week 16
|
2.78 units on a scale
Standard Error 0.70
|
4.27 units on a scale
Standard Error 0.66
|
4.57 units on a scale
Standard Error 0.67
|
5.07 units on a scale
Standard Error 0.64
|
|
SF-36v2 - Physical Component
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24)
|
5.50 units on a scale
Standard Error 0.67
|
5.23 units on a scale
Standard Error 0.64
|
5.85 units on a scale
Standard Error 0.67
|
6.06 units on a scale
Standard Error 0.63
|
SECONDARY outcome
Timeframe: Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phasePopulation: 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.
Patient Global Impression of Change; 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=70 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=78 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=75 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Number of Participants in Each Category of PGIC
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) · Minimally worse
|
3 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants in Each Category of PGIC
Week 16 · Very much improved
|
6 Participants
|
19 Participants
|
17 Participants
|
24 Participants
|
|
Number of Participants in Each Category of PGIC
Week 16 · Much improved
|
16 Participants
|
34 Participants
|
34 Participants
|
31 Participants
|
|
Number of Participants in Each Category of PGIC
Week 16 · Minimally improved
|
22 Participants
|
15 Participants
|
16 Participants
|
19 Participants
|
|
Number of Participants in Each Category of PGIC
Week 16 · No change
|
18 Participants
|
7 Participants
|
7 Participants
|
7 Participants
|
|
Number of Participants in Each Category of PGIC
Week 16 · Minimally worse
|
5 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants in Each Category of PGIC
Week 16 · Much worse
|
2 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants in Each Category of PGIC
Week 16 · Very much worse
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants in Each Category of PGIC
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) · Very much improved
|
17 Participants
|
21 Participants
|
23 Participants
|
25 Participants
|
|
Number of Participants in Each Category of PGIC
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) · Much improved
|
26 Participants
|
37 Participants
|
24 Participants
|
40 Participants
|
|
Number of Participants in Each Category of PGIC
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) · Minimally improved
|
19 Participants
|
13 Participants
|
15 Participants
|
6 Participants
|
|
Number of Participants in Each Category of PGIC
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) · No change
|
3 Participants
|
3 Participants
|
4 Participants
|
6 Participants
|
|
Number of Participants in Each Category of PGIC
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) · Much worse
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants in Each Category of PGIC
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24) · Very much worse
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Week 16 of the double-blind treatment phase; Week 24 of the open-label extension phasePopulation: 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=69 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=78 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=73 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Number of Participants Eligible for Nasal Polyp Surgery
Week 16
|
23 Participants
|
13 Participants
|
13 Participants
|
17 Participants
|
|
Number of Participants Eligible for Nasal Polyp Surgery
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24)
|
13 Participants
|
9 Participants
|
12 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Week 16 of the double-blind treatment phase; Week 24 of the open-label extension phasePopulation: 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. Change from baseline in Peak Nasal Inspiratory Flow (PNIF)
Outcome measures
| Measure |
Placebo
n=67 Participants
Matched placebo BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 100 mcg
n=79 Participants
OPN-375 100 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 200 mcg
n=74 Participants
OPN-375 200 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
OPN-375 400 mcg
n=81 Participants
OPN-375 400 mcg BID x 16 weeks, then OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|
|
Peak Nasal Inspiratory Flow (PNIF)
Week 16
|
0.54 L/min
Standard Error 5.37
|
26.50 L/min
Standard Error 5.12
|
24.92 L/min
Standard Error 5.25
|
28.64 L/min
Standard Error 5.04
|
|
Peak Nasal Inspiratory Flow (PNIF)
Week 24 (all pts on OPN-375 400 mcg BID wks 17-24)
|
15.34 L/min
Standard Error 5.42
|
32.06 L/min
Standard Error 5.20
|
31.87 L/min
Standard Error 5.36
|
33.08 L/min
Standard Error 5.13
|
Adverse Events
Placebo (Double-blind Phase)
Serious events: 1 serious events
Other events: 38 other events
Deaths: 0 deaths
OPN-375 100 mcg (Double-blind Phase)
Serious events: 0 serious events
Other events: 39 other events
Deaths: 0 deaths
OPN-375 200 mcg (Double-blind Phase)
Serious events: 0 serious events
Other events: 39 other events
Deaths: 0 deaths
OPN-375 400 mcg (Double-blind Phase)
Serious events: 1 serious events
Other events: 46 other events
Deaths: 0 deaths
OPN-375 400 mcg (Open-label Phase)
Serious events: 0 serious events
Other events: 60 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo (Double-blind Phase)
n=79 participants at risk
Matched placebo BID x 16 weeks
|
OPN-375 100 mcg (Double-blind Phase)
n=80 participants at risk
OPN-375 100 mcg BID x 16 weeks
|
OPN-375 200 mcg (Double-blind Phase)
n=80 participants at risk
OPN-375 200 mcg BID x 16 weeks
|
OPN-375 400 mcg (Double-blind Phase)
n=82 participants at risk
OPN-375 400 mcg BID x 16 weeks
|
OPN-375 400 mcg (Open-label Phase)
n=299 participants at risk
OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|---|
|
Infections and infestations
Meningitis and Sinusitis
|
1.3%
1/79
|
0.00%
0/80
|
0.00%
0/80
|
0.00%
0/82
|
0.00%
0/299
|
|
Nervous system disorders
Positional vertigo
|
0.00%
0/79
|
0.00%
0/80
|
0.00%
0/80
|
1.2%
1/82
|
0.00%
0/299
|
Other adverse events
| Measure |
Placebo (Double-blind Phase)
n=79 participants at risk
Matched placebo BID x 16 weeks
|
OPN-375 100 mcg (Double-blind Phase)
n=80 participants at risk
OPN-375 100 mcg BID x 16 weeks
|
OPN-375 200 mcg (Double-blind Phase)
n=80 participants at risk
OPN-375 200 mcg BID x 16 weeks
|
OPN-375 400 mcg (Double-blind Phase)
n=82 participants at risk
OPN-375 400 mcg BID x 16 weeks
|
OPN-375 400 mcg (Open-label Phase)
n=299 participants at risk
OPN-375 400 mcg (open-label) BID x 8 weeks
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis (identified by investigator on routine nasal endoscopy)
|
3.8%
3/79
|
12.5%
10/80
|
8.8%
7/80
|
9.8%
8/82
|
5.7%
17/299
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis (spontaneously reported by subject)
|
1.3%
1/79
|
5.0%
4/80
|
15.0%
12/80
|
12.2%
10/82
|
3.0%
9/299
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.5%
2/79
|
2.5%
2/80
|
6.2%
5/80
|
3.7%
3/82
|
0.67%
2/299
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
3.8%
3/79
|
1.2%
1/80
|
1.2%
1/80
|
1.2%
1/82
|
0.00%
0/299
|
|
Gastrointestinal disorders
Toothache
|
1.3%
1/79
|
0.00%
0/80
|
0.00%
0/80
|
2.4%
2/82
|
0.00%
0/299
|
|
Infections and infestations
Acute sinusitis
|
2.5%
2/79
|
0.00%
0/80
|
1.2%
1/80
|
0.00%
0/82
|
1.0%
3/299
|
|
Infections and infestations
Bronchitis
|
2.5%
2/79
|
2.5%
2/80
|
2.5%
2/80
|
1.2%
1/82
|
1.0%
3/299
|
|
Infections and infestations
Influenza
|
2.5%
2/79
|
1.2%
1/80
|
2.5%
2/80
|
2.4%
2/82
|
0.00%
0/299
|
|
Infections and infestations
Nasopharyngitis
|
5.1%
4/79
|
2.5%
2/80
|
1.2%
1/80
|
9.8%
8/82
|
1.0%
3/299
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/79
|
2.5%
2/80
|
1.2%
1/80
|
2.4%
2/82
|
0.00%
0/299
|
|
Infections and infestations
URTI
|
12.7%
10/79
|
5.0%
4/80
|
7.5%
6/80
|
4.9%
4/82
|
1.0%
3/299
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/79
|
2.5%
2/80
|
1.2%
1/80
|
0.00%
0/82
|
0.00%
0/299
|
|
Investigations
Intraocular pressure increased
|
0.00%
0/79
|
1.2%
1/80
|
3.8%
3/80
|
1.2%
1/82
|
1.3%
4/299
|
|
Nervous system disorders
Headache
|
3.8%
3/79
|
6.2%
5/80
|
7.5%
6/80
|
7.3%
6/82
|
0.33%
1/299
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/79
|
0.00%
0/80
|
1.2%
1/80
|
3.7%
3/82
|
0.33%
1/299
|
|
Respiratory, thoracic and mediastinal disorders
Nasal mucosal disorder
|
2.5%
2/79
|
7.5%
6/80
|
10.0%
8/80
|
6.1%
5/82
|
2.0%
6/299
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum disorder
|
2.5%
2/79
|
6.2%
5/80
|
5.0%
4/80
|
4.9%
4/82
|
1.3%
4/299
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum ulceration
|
3.8%
3/79
|
3.8%
3/80
|
7.5%
6/80
|
9.8%
8/82
|
3.0%
9/299
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/79
|
2.5%
2/80
|
0.00%
0/80
|
0.00%
0/82
|
0.00%
0/299
|
Additional Information
Vice President Global Clinical Operations & Outsourcing
OptiNose
Phone: 267-364-3508
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place