Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Rhinosinusitis Without the Presence of Nasal Polyps

Chronic Rhinosinusitis Clinical Trial

Official title:

A 24-Week Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 186 and 372 μg of OPN-375 Twice a Day (BID) in Subjects With Chronic Rhinosinusitis Without the Presence of Nasal Polyps

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03960580
• Other study ID #: OPN-FLU-CS-3206
• Status: Completed
• Phase: Phase 3
• Start date: June 6, 2019
• Est. completion date: May 4, 2022

Study information

• Verified date: December 2023
• Source: Optinose US Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 24-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of intranasal administration of 186 and 372 μg twice daily (BID) of OPN-375 in subjects with chronic Rhinosinusitis (CRS) without nasal polyps

Description:

The primary objective of this study is to compare the efficacy of intranasal administration of twice-daily doses of 186 and 372 µg of OPN-375 (fluticasone propionate) with placebo in subjects with chronic rhinosinusitis using the following co-primary endpoints:

1. A change from baseline in symptoms as measured by the average morning composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4.

2. A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: May 4, 2022
• Est. primary completion date: May 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. men or women aged 18 years and older at baseline visit

2. women of child bearing potential must be abstinent, or if sexually active,

1. be practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], or male partner sterilization) before entry and throughout the study, or

2. be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or

3. be postmenopausal (amenorrhea for at least 1 year)

3. women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening)

4. must have a history of chronic sinusitis and be currently experiencing 2 or more of the following symptoms, 1 of which has to be either nasal congestion or nasal discharge (anterior and/or posterior nasal discharge) for equal to or greater than 12 weeks:

• nasal congestion

• nasal discharge (anterior and/or posterior nasal discharge)

• facial pain or pressure

• reduction or loss of smell

5. endoscopic evidence of nasal mucosal disease, with edema or purulent discharge; or polyps/polypoid tissue <Grade 1 in middle meatus, bilaterally

6. must have confirmatory evidence via a computed tomography(CT) scan of bilateral sinus disease (have at least 1 sinus on each side of nose with a Lund-Mackay score of =1)

7. baseline CT scan must show a combined =25% opacification of the ethmoid sinuses and =25% opacification of at least 1 maxillary sinus

8. must have at least moderate symptoms (as defined in protocol) of nasal congestion as reported by the subject, on average, for the 7-day period preceding Visit 1 (Screening) run-in

9. must have an average morning score of at least 1.5 for congestion on the Nasal Symptom Scale (as defined in protocol) recorded on the subject diary over a 7-day period during the first 14 days of the single-blind run-in period

10. must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization

11. Subjects with comorbid asthma or chronic obstructive pulmonary disorder (COPD) must be stable with no exacerbations (eg, no emergency room visits, hospitalizations, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Inhaled corticosteroid use must be limited to stable doses of no more than 1,000 µg/day of beclomethasone (or equivalent) for at least 3 months before Visit 1 (Screening) with plans to continue use throughout the study.

12. Subjects with aspirin-exacerbated respiratory disease, who have undergone aspirin desensitization and are receiving daily aspirin therapy, must be receiving therapy for at least 6 months prior to Visit 1.

13. must be able to cease treatment with intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at the screening visit.

14. must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening)

15. must be able to use the exhalation delivery system correctly; all subjects will be required to demonstrate correct use with the practice exhalation delivery system (EDS) at Visit 1 (Screening).

16. must be capable, in the opinion of the investigator, of providing informed consent to participate in the study. Subjects must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

1. women who are pregnant or lactating

2. inability to have each nasal cavity examined for any reason, including nasal septum deviation

3. inability to achieve bilateral nasal airflow

4. is currently taking XHANCE®

5. have previously used XHANCE® for more than 1 month and did not achieve an adequate symptomatic response

6. the nasal/sinus anatomy prevents the accurate assessment of sinus volume via CT scan

7. history of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery

8. have current evidence of odontogenic sinusitis, sinus mucocele (the affected sinus is completely opacified and either the margins are expanded and/or thinned OR there are areas of complete bone resorption resulting in bony defect and extension of the "mass" into adjacent tissues), evidence of allergic fungal sinusitis, or evidence of complicated sinus disease (including, but not limited to, extension of inflammation outside of the sinuses and nasal cavity)

9. have a paranasal sinus or nasal tumor

10. have polyp grade =1 (polyp that is free on 5 sides and has a stalk) on either side of the nose as determined by the nasoendoscopy at screening

11. have a nasal septum perforation

12. have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening)

13. have evidence of significant mucosal injury, ulceration (eg, exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy

14. have current, ongoing rhinitis medicamentosa (rebound rhinitis)

15. have significant oral structural abnormalities (eg, a cleft palate)

16. have a diagnosis of cystic fibrosis

17. history of Churg-Strauss syndrome or dyskinetic ciliary syndromes

18. symptom resolution or last dose of antibiotics for purulent nasal infection, acute sinusitis, or upper respiratory tract infection has not occurred before Visit 1 or was less than 4 weeks before the CT scan. Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution.

19. planned sinonasal surgery during the period of the study

20. allergy, hypersensitivity, or contraindication to corticosteroids or steroids

21. has used oral steroids in the past for treatment of chronic sinusitis and did not experience any relief of symptoms

22. has a steroid eluting sinus stent still in place within 30 days of Visit 1

23. allergy or hypersensitivity to any excipients in study drug

24. exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral, intraarticular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD

25. have nasal candidiasis

26. history or current diagnosis of any form of glaucoma or ocular hypertension

27. history of intraocular pressure elevation on any form of steroid therapy

28. history or current diagnosis of the presence (in either eye) of a subcapsular cataract

29. history of immunodeficiency

30. any serious or unstable concurrent disease, psychiatric disorder, or any significant condition that, in the opinion of the investigator could confound the results of the study or could interfere with the subject's participation or compliance in the study

31. have a positive drug screen or a recent (within 1 year of Visit 1 [Screening]) history of drug or alcohol abuse, or dependence that, in the opinion of the investigator could interfere with the subject's participation or compliance in the study

32. have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)

33. have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1 (Screening)

34. is using strong cytochrome P450 3A4 (CYP3A4) inhibitors (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole)

35. is an employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or is a family member of the employee or the investigator.

36. patients who report unexplained worsening of vision within the past 3 months (e.g. difficulty reading or seeing traffic signs from a distance). A diagnosis of presbyopia established by an eye care professional is not exclusionary.

Related Conditions & MeSH terms

• Chronic Rhinosinusitis
• Nasal Polyps
• Sinusitis

Intervention

Drug:
• OPN-375
OPN-375, BID

Locations

Country	Name	City	State
Australia	Otopure Pty Ltd	Bella Vista	New South Wales
Australia	Casey Superclinic	Berwick	Victoria
Australia	Vale Medical Practice	Brookvale	New South Wales
Australia	Browns Plains Family Practice	Browns Plains	Queensland
Australia	Camberwell Road Medical Practice	Hawthorn East	Victoria
Australia	Australian Clinical Research Network	Maroubra	New South Wales
Australia	Mirrabooka Medical Centre	Mirrabooka	Western Australia
Australia	Latitude Clinical Research	Spearwood	Western Australia
Bulgaria	UMHAT Kaspela EOOD	Plovdiv
Bulgaria	DCC Convex EOOD	Sofia
Bulgaria	MC N.I. Pirogov EOOD	Sofia
Bulgaria	Medical Center Iskar EOOD	Sofia
Bulgaria	MHAT - Central Clinical Base Sofia Medical Institute Ministry of Interior	Sofia
Bulgaria	MHAT Serdika EOOD	Sofia
Bulgaria	MMA MHAT - Sofia	Sofia
Bulgaria	MHAT Trakiya EOOD	Stara Zagora
Bulgaria	DCC "Mladost - M Varna" OOD	Varna
Czechia	Nemocnice Rudolfa a Stefanie Benesov, a.s., ORL oddeleni	Benesov
Czechia	FN Hradec Kralove, Klinika ORL	Hradec Králové
Czechia	Pro-audio s.r.o.	Mladá Boleslav
Czechia	MUDr. Pavel Navratil, ORL ambulance	Olomouc
Czechia	Nemocnice Pardubického kraje - Pardubická nemocnice	Pardubice
Czechia	AXON Clinical s.r.o.	Prague
Czechia	VFN v Praze, oddeleni ORL	Praha
Georgia	JSC Curatio	Tbilisi
Georgia	Ltd Acad. Fridon Todua Medical Center- Research	Tbilisi
Georgia	Ltd Aversi Clinic	Tbilisi
Georgia	Ltd Israel-Georgian Medical Research Clinic - Helsicore	Tbilisi
Georgia	Ltd New Hospitals	Tbilisi
Georgia	Ltd Simon Khechinashvili University Hospital	Tbilisi
Georgia	Ltd Tbilisi Heart Center	Tbilisi
New Zealand	Optimal Clinical Trials	Auckland
New Zealand	Clinical Trials New Zealand	Hamilton
New Zealand	P3 Research Tauranga Ltd.	Tauranga	Bay Of Plenty
New Zealand	P3 Research Wellington Ltd.	Wellington
Poland	Centrum Medyczne MedSen Sp. z o.o.	Bialystok
Poland	ReumaClinic Gabinet Reumatologiczny	Bialystok
Poland	Centrum Medyczne Kwiatowa	Bydgoszcz
Poland	Synexus Polska Sp. Z o. o., Oddzial w Gdyni ul. Luzycka 3c	Gdynia
Poland	Przychodnia "Narutowicza"	Inowroclaw	Kujawsko-Pomorskie
Poland	Centrum Medyczne Angelius Provita	Katowice
Poland	Indywidualna Specjalistyczna Praktyka Lekarska J. Slifirski	Kety	Malopolskie
Poland	Centrum Medyczne All-Med	Kraków	Malopolskie
Poland	Mini-Clinic Pawel Bialoglowski	Lancut
Poland	Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna	Lublin
Poland	Centrum Medyczne Lucyna Andrzej Dymek S.C.	Strzelce Opolskie
Poland	NZOZ "Ignis" dr med. Alicja Lobinska	Swidnik
Poland	NZOZ Przychodnia Medycyny Rodzinnej	Swietochlowice
Poland	NZOZ Centrum Medyczne LiMED	Tarnowskie Góry
Poland	Synexus Polska Sp. z.o.o. Oddzial w Warszawie	Warszawa
Poland	Synexus Polska Sp.zo.o. Oddzial we Wroclawiu	Wroclaw
Romania	S.C. Centrul Medical Unirea S.R.L. Brasov	Brasov
Romania	S.C. Euroclinic Hospital S.A.	Bucharest
Romania	SC Centrul Medical Unirea srl, Policlinica Primaverii	Bucharest
Romania	Centrul Medical Cardiomed Cluj, Cabinet ORL	Cluj-Napoca
Romania	Spitalul Clinic Universitar CF Cluj-Napoca	Cluj-Napoca
Romania	S.C. Centrul Medical Unirea S.R.L - IASI, Campus Medical Iasi - Cabinet ORL	Iasi
Spain	Centro Médico Teknon	Barcelona
Spain	Hospital Universitari Clinic de Barcelona	Barcelona
Spain	Hospital Universitario de Fuenlabrada Servicio de Otorrinolaringología	Fuenlabrada	Madrid
Spain	Hospital Universitario de Jerez de la Frontera	Jerez De La Frontera	Cadiz
Spain	Hospital Universitari de Bellvitge, Servicio de Otorrinolaringología	L'Hospitalet De Llobregat
Spain	Consulta 164 Servicio ORL Hospital Clinico Universitario de Santiago de Compostela	Santiago De Compostela
Spain	Hospital Universitario Virgen Macarena	Seville
Spain	Hospital Universitario de Torrejon	Torrejon de Ardoz	Madrid
Spain	Hospital Universitario i Politecnic la Fe	Valencia
United Kingdom	King's Mill Hospital	Sutton-in-Ashfield	Nottinghamshire
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Treasure Valley Medical Research	Boise	Idaho
United States	Asthma and Allergy Associates	Colorado Springs	Colorado
United States	University of Missouri, Dept of Otorlaryngology	Columbia	Missouri
United States	Sacramento Ear, Nose & Throat Surgical and Medical Group Inc	Folsom	California
United States	Allergy, Asthma & Sinus Center, SC	Greenfield	Wisconsin
United States	Pasha Snoring & Sinus Center	Houston	Texas
United States	BioSolutions Clinical Research Center	La Mesa	California
United States	Sher Allergy Specialists	Largo	Florida
United States	Veterans Administration Greater Los Angeles Healthcare System	Los Angeles	California
United States	Charlotte Eye Ear Nose and Throat Assoc., PA	Matthews	North Carolina
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Best Clinical Trials	New Orleans	Louisiana
United States	Mount Sinai Downtown Union Square	New York	New York
United States	Northwell Health at ENT and Allergy Associates	New York	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Sacramento Ear, Nose & Throat Surgical and Medical Group	Roseville	California
United States	University of Utah	Salt Lake City	Utah
United States	ENT & Allergy Partners, LLC	Summerville	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Optinose US Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Czechia,  Georgia,  New Zealand,  Poland,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of Safety by Recording the Severity of Adverse Events (AEs)	Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe	24 Weeks
Other	Evaluation of Safety-Nasal Examination	Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum.	24 Weeks
Other	Evaluation of Safety Measuring Vital Signs- Blood Pressure	Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)	24 Weeks
Other	Evaluation of Safety Measuring Vital Signs- Pulse	Measure pulse in beats per minute (bpm)	24 Weeks
Other	Evaluation of Safety Measuring Vital Signs- Weight	Assessment of safety from physical examination-weight measured in kg or lb	24 Weeks
Other	Evaluation of Safety - Monitoring Concomitant Medication Usage	Assessment for safety from the collection of information for concomitant medications usage. Top 5 reported con-meds by therapeutic class are listed for this outcome.	24 Weeks
Primary	Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4	Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.	4 Weeks
Primary	Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses.	Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent volume opacified can range from 0% to 100%. Outcome measure is the percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.	Baseline, Week 24
Secondary	Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous).	The 4 individual CRS symptoms are: congestion, facial pain or pressure sensation, nasal discharge (anterior and/or posterior), and sense of smell. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. The scores at baseline and week 4 are calculated by averaging the score reported for the individual symptom over 7 days prior to the timepoint. The value provided in the results is calculated by subtracting the score at Week 4 from the score at Baseline; therefore, scores reported here can range from -3 to 3.	Baseline, Week 4
Secondary	Time to First Acute Exacerbation of Chronic Sinusitis	Comparing the distribution of time to first acute exacerbation of chronic sinusitis across treatment groups. An exacerbation of chronic sinusitis is defined as a worsening of symptoms that requires escalation of treatment.	24 Weeks
Secondary	Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains	The SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional consequences of their nasal disorder across several domains including: rhinologic, extra-nasal rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. The score range for each domain are as follows: Rhinologic: 0-30; Extra-nasal rhinologic: 0-15; Ear/facial: 0-25; Psychological dysfunction: 0-35; Sleep dysfunction: 0-25. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be, and total scores are calculated by adding scores together. The values reported here are calculated by subtracting the score reported at baseline from the score reported at Week 24 and, therefore, can range from the negative maximum score value to the positive maximum score value.	24 Weeks
Secondary	Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery.	Change from baseline in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Range of scores for each symptom is 0=none, 1=mild, 2=moderate, 3=severe. The composite score is the sum of the 3 symptom scores and will range from 0-9. Scores reported at each timepoint are the averaged total instantaneous AM scores over the last 7 days before the given timepoint. The values presented here are calculated by subtracting the score at Baseline from Week 8 and Week 12, respectively.	8 weeks, 12 weeks.
Secondary	Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores	Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.	8 Weeks; 12 Weeks
Secondary	Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores	Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) scores. The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living	Baseline, Week 8, Week 12
Secondary	Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores	Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.	Baseline, Week 8, Week 12
Secondary	Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores	Subjects will report instantaneous (evaluation of symptom severity immediately preceding the time of scoring) symptoms. The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent.	Baseline, Week 8, Week 12
Secondary	Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery	Change from Baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT for subgroups in patients without and without previous sinus surgery. Percent volume opacified of the combined ethmoid and maxillary sinuses can range from 0% to 100%. Outcome measure is percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score	Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for each of the left and right ostiomeatal complex (OMC). The total LM score for a CT scan ranges from 0-24.	Baseline, Week 24
Secondary	Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair	Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification).; Each sinus pair (left and right side) listed below can achieve a total score of 0-4 (sum of 0-2 for each side). The values reported below are calculated by subtracting the total score at baseline from the total score at Visit 6 (week 24).	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment.	Percent volume opacified of the worst maxillary sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst maxillary sinus at baseline to the percent opacification of the same maxillary sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%.	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment.	Percent volume opacified of the worst ethmoid sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst ethmoid sinus at baseline to the percent opacification of the same ethmoid sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%.	24 weeks
Secondary	Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment.	Percent volume opacified of the worst sinus can range from 0% to 100%. The outcome measure is the percentage change from percent opacification of the worst sinus at baseline to the percent opacification of the same sinus at Week 24; therefore, change in opacification volume can range from -100% to 100%.	24 weeks
Secondary	Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined	Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for each of the left and right ostiomeatal complex (OMC).; The values reported for this outcome are the change in total opacification of the left an dright maxillary and ethmoid sinuses (Visit 6 [Wk 24] score minus Baseline score). Each visit score can range from a total of 0-12 (sum of 0-2 score assigned for each of left and right maxillary, left and right anterior ethmoid, and left and right posterior ethmoid).	24 Weeks
Secondary	Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score	Zinreich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% for each each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal). Total score ranges from 0 to 50.	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs.	Zinreich Modification of the Lund-Mackay Staging System: Zinreich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100%. Each of the following sinus pairs can achieve a total score of 0-10 (sum of score on each left and right side): anterior ethmoids, posterior ethmoids, maxillary sinuses, frontal sinuses, sphenoid sinuses.; The values reported for this outcome are calculated by subtracting the score at baseline from the score at Visit 6 (Wk 24).	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined	Zinreich Modification of the Lund-Mackay Staging System: Zinreich modified the LM system by creating subdivisions with "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0=0%, 1=1%-25%, 2=26%-50%, 3=51%-75%, 4=76%-99%, and 5=100%. The total score for the combined ethmoids and maxillary sinuses can range from 0-30 (0-5 for each left and right of the anterior ethmoid, posterior ethmoid, and maxillary sinuses). The outcome values presented in the results were determined by subtracting the total score at Baseline from the total score at Week 24.	24 weeks
Secondary	Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations	Zinreich Modification of the Lund-Mackay Staging System: Zinreich modified the LM system by creating subdivisions with "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0=0%, 1=1%-25%, 2=26%-50%, 3=51%-75%, 4=76%-99%, and 5=100%.; Data provided for full population and with and without prior sinus surgery subgroups. Number of participants analyzed in the subgroups will be less than the total overall, as these are only portions of the total population.	24 Weeks
Secondary	Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)	The PSQI is a validated, self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate 7 "component" scores (each ranging between 0 and 3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging between 0 and 21. Higher values represent a worse outcome.	12 Weeks, 24 Weeks
Secondary	Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC)	Global impression of change will be assessed using a subject-completed PGIC scale range: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse. Values provided for this outcome measure are the percentage of subjects reporting a score of 1 - Very much improved, 2 - Much improved, or 3 - Minimally improved at each timepoint.	Week 4, Week 24
Secondary	Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)	The SF-36v2 is a multipurpose, 36-item subject-completed validated questionnaire that measures 8 domains of health: physical functioning, role limitations due to physical health (RP), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The SF-36v2 survey with a 4-week recall will be used. It yields scale scores for each of these 8 health domains , each of which is scored from 0 to 100. Higher scores indicate a better health status, with 100 representing the highest level of functioning possible.	24 Weeks
Secondary	Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS).	Change from baseline to Week 24/ET on the MCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability. Result values are calculated by subtracting the score reported at Week 24 from the score reported at Baseline.	24 Weeks
Secondary	Change in the SF-36v2 Physical Component Score (PCS)	Change from baseline to Week 24/ET on the PCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability. Result values are calculated by subtracting the score reported at Week 24 from the score reported at Baseline.	24 Weeks
Secondary	Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS)	The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, where higher scores indicate a worse outcome.	24 Weeks
Secondary	Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)	The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, where higher scores indicate a worse outcome. Results reported for this outcome measure are the	24 Weeks
Secondary	Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™	The SIT is a test comprised of 4 booklets each containing 10 microencapsulated (scratch and sniff) odors. Forced choice response alternatives accompany each test item. Each correct response is assigned a score of 1 and incorrect responses are assigned a score of 0. The total score is calculated by summing the scores of each individual odor for a total possible score ranging from 0-40. The higher the score, the better the individual's sense of smell. The test provides an absolute indication of smell loss (anosmia; mild, moderate or sever hyposmia) as well as an index to detect malingering.	24 Weeks
Secondary	Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument	The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The outcome measured for this study was the EQ VAS, which records the subject's self-rated health on a vertical visual analogue scale, where the endpoints are labelled "The best health you can imagine" and "The worst health you can imagine". The VAS can be used as a quantitative measure of health outcome that reflects the subject's own judgement. VAS scores range from 0 (worst health you can imagine) to 100 (best health you can imagine).	24 Weeks
Secondary	Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument	The SF-6D is a single health state index derived from the 11 items from the SF-36v2. SF-6D scores range from 0 (worst health state) to 1 (best health state). The values provided in the outcome data are calculated by subtracting the score reported at baseline from the score reported at Visit 6 (Week 24).	24 Weeks
Secondary	Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24	Percentage of subjects indicating that they are willing to consider Sinus Surgery. This is a comparison of health economic measures and data was obtained by direct questioning of the subjects during study visits.	Baseline, Week 24
Secondary	Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24.	Percentage of subjects who meet the minimal objective criteria for surgical intervention based on completion of a surgical intervention assessment questionnaire for the investigator.	Baseline, Week 24
Secondary	Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery	Outcome value presented here is the percent of subjects who are approved for surgery but no longer elect to undergo a surgery. Number of participants analyzed indicates the total number of participants for whom this analysis was completed.	Week 24