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

Potential subjects must meet the following criteria to enter this study:

• men or women aged 18 years and older at baseline visit
• women of childbearing potential must be abstinent, or if sexually active,
• be practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], or male partner sterilization) before entry and throughout the study, or
• be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
• be postmenopausal (amenorrhea for at least 1 year)
• women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening)
• must have a history of chronic rhinosinusitis (CRS) 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
• endoscopic evidence of nasal mucosal disease, with edema, purulent discharge, or polyps in middle meatus, bilaterally, or presence of bilateral disease on a prior computed tomography (CT) scan performed within 14 days of Visit 1
• must have confirmatory evidence via a CT scan of bilateral sinus disease (have at least 1 sinus on each side of nose with a Lund-Mackay score of ≥1)
• baseline CT scan must show a combined ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus
• 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
• 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
• must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization
• Subjects with comorbid asthma or 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.
• 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.
• must be able to cease treatment with intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at the screening visit
• must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening)
• must be able to use the exhalation delivery system (EDS) correctly; all subjects will be required to demonstrate correct use with the practice EDS at Visit 1 (Screening).
• 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.

Potential subjects who meet any of the following criteria will be excluded from entering this study:

• women who are pregnant or lactating
• inability to have each nasal cavity examined for any reason, including nasal septum deviation
• inability to achieve bil