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 Sinusitis With or Without the Presence of Nasal Polyps
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 sinusitis (CS) with or without nasal polyps.
1. A change from baseline in symptoms as measured by a 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.
18 Years and up
Accepting Healthy Volunteers?
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 before entry and throughout the study, or
2. be surgically sterile, 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, purulent discharge, or polyps 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 (as defined in protocol) recorded on the subject diary for a 7 days period of the single-blind run-in
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. must be able to cease treatment with oral steroids, intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at the baseline visit
13. must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening)
14. must be able to use the exhalation delivery system correctly; all subjects will be required to demonstrate correct use of the practice exhalation delivery system (EDS) at Visit 1 (Screening).
15. 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.
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 sinus mucocele or evidence of allergic fungal sinusitis
9. have a polyp extending outside the ostiomeatal complex/middle turbinate (anterior or inferior) that is below the inferior turbinate attachment as determined by the nasoendoscopy at screening
10. have a nasal septum perforation
11. have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening)
12. have evidence of significant mucosal injury, ulceration (eg exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy
13. have current, ongoing rhinitis medicamentosa (rebound rhinitis)
14. have significant oral structural abnormalities (eg, a cleft palate)
15. have a diagnosis of cystic fibrosis
16. history of Churg-Strauss syndrome or dyskinetic ciliary syndromes
17. symptom resolution or last dose of antibiotics for purulent nasal infection, acute sinusitis, or upper respiratory tract infection was less than 4 weeks prior to Visit 1 (Screening). Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution.
18. planned sinonasal surgery during the period of the study
19. allergy, hypersensitivity, or contraindication to corticosteroids or steroids
20. has used oral steroids in the past for treatment of chronic sinusitis and did not experience any relief of symptoms
21. has a steroid eluting sinus stent still in place within 30 days of Visit 1
22. allergy or hypersensitivity to any excipients in study drug
23. exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral, intra-articular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD
24. have nasal candidiasis
25. history or current diagnosis of any form of glaucoma or ocular hypertension (intraocular pressure at screening of >21)
26. history of intraocular pressure elevation on any form of steroid therapy
27. history or current diagnosis of the presence (in either eye) of a sub-capsular cataract
28. history of immunodeficiency
29. 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
30. 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
31. have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
32. have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1 (Screening)
33. is using strong cytochrome P450 3A4 (CYP3A4) inhibitor (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole)
34. 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