Study Evaluating the Efficacy and Safety of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Twice a Day (BID) Using a Novel Bi Directional Device in Subjects With Bilateral Nasal Polyposis Followed by an 8-Week Open-Label Extension Phase to Assess Safety
Condition: Bilateral Nasal Polyposis
MeSH terms: Colorectal Neoplasms; Nasopharyngeal Neoplasms; Nasal Polyps
Intervention: Fluticasone Propionate
Intervention description: Delivered via Optinose Exhalation Delivery System
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 323.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to compare the efficacy of intranasal administration
      of 100, 200, and 400 μg of fluticasone propionate twice a day delivered by the OptiNose
      device with placebo in subjects with bilateral nasal polyposis. Two co-primary endpoints will
      be used in the study: reduction of nasal congestion/obstruction symptoms at the end of Week 4
      of the double-blind treatment phase measured by the 7 day average instantaneous AM diary
      symptom scores, and reduction in total polyp grade (sum of scores from both nasal cavities)
      over the 16 weeks of the double-blind treatment phase as determined by the Lildholdt scale
      score measured by nasoendoscopy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men or women aged 18 years and older

          -  Women must

               -  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, or
                  tubal ligation at least 1 year before screening) or otherwise be incapable of
                  pregnancy, or

               -  be postmenopausal (spontaneous amenorrhea for at least 1 year).

          -  Women of child-bearing potential must have a negative serum beta-human chorionic
             gonadotropin (B-hCG) or urine pregnancy test (depending on local regulations) at the
             screening visit

          -  Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal
             cavities as determined by the Lildholdt scale score measured by nasoendoscopy at both
             screening and baseline visits

          -  Must have at least moderate symptoms of nasal congestion/obstruction as reported by
             the subject for the 7 day period preceding the screening visit

          -  At the baseline visit (Day 1), must have a morning score of at least 2 (moderate) on
             nasal congestion/obstruction recorded on the subject diary for at least 5 of the last
             7 days of the 7 to up to 14 day 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 COPD must be stable with no exacerbations (eg, no
             emergency room visits, hospitalizations, or oral or parenteral steroid use) within the
             3 months before the screening visit. 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 screening with plans to continue use throughout the study.

          -  Must be able to cease treatment with intranasal medications including, but not limited
             to, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium
             bromide, inhaled corticosteroids (except permitted doses listed above for comorbid
             asthma and COPD) at the screening visit

          -  Must be able to cease treatment with oral and nasal decongestants and antihistamines
             at the screening visit

          -  Must be able to use the OptiNose device correctly; all subjects will be required to
             demonstrate correct use of the placebo device at screening, Visit 1.

          -  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:

          -  Women who are pregnant or lactating

          -  Have complete or near-complete obstruction of the nasal cavities

          -  Inability to achieve bilateral nasal airflow for any reason including nasal septum
             deviation

          -  Inability to have each nasal cavity examined for any reason including nasal septum
             deviation

          -  Nasal septum perforation

          -  Has had more than 1 episode of epistaxis with frank bleeding in the month before the
             screening visit

          -  Have evidence of significant baseline mucosal injury, ulceration or erosion (eg,
             exposed cartilage, perforation) on baseline nasal examination/nasal endoscopy

          -  History of more than 5 sinonasal surgeries for either nasal polyps or nasal/sinus
             inflammation (lifetime)

          -  History of sinus or nasal surgery within 6 months before the screening visit

          -  History of any surgical procedure that prevents the ability to accurately grade polyps

          -  Have symptoms of seasonal allergic rhinitis at screening or baseline and/or, based on
             time of year, would anticipate onset of symptoms within 4 weeks of randomization

          -  Current, ongoing rhinitis medicamentosa (rebound rhinitis)

          -  Have significant oral structural abnormalities, eg, a cleft palate

          -  Diagnosis of cystic fibrosis

          -  History of Churg-Strauss syndrome or dyskinetic ciliary syndromes

          -  Purulent nasal infection, acute sinusitis, or upper respiratory tract infection within
             2 weeks before the screening visit. Potential subjects presenting with any of these
             infections may be rescreened 4 weeks after symptom resolution Note: Subjects who are
             taking prophylactic antibiotics will be allowed to enter the study as long as they
             intend to continue the antibiotics for the duration of the study.

          -  Planned sinonasal surgery during the period of the study

          -  Allergy, hypersensitivity, or contraindication to corticosteroids or steroids

          -  Allergy or hypersensitivity to any excipients in study drug

          -  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 the screening visit; except as noted in inclusion criteria for
             subjects with comorbid asthma or COPD

          -  Have nasal candidiasis

          -  Have taken a potent CYP3A4 inhibitor within 14 days before the screening visit.

          -  History or current diagnosis of any form of glaucoma or ocular hypertension (ie, >21
             mmHg)

          -  History of intraocular pressure elevation on any form of steroid therapy

          -  History or current diagnosis of the presence (in either eye) of a cataract

          -  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

          -  A recent (within 1 year of the screening visit) clinically significant history of drug
             or alcohol use, abuse, or dependence that, in the opinion of the investigator could
             interfere with the subject's participation or compliance in the study

          -  Positive urine drug screen at screening visit for drugs of abuse, with the exception
             of prescribed medications for legitimate medical conditions

          -  Have participated in an investigational drug clinical trial within 30 days of the
             screening visit

          -  Employees 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, as
             well as family members of the employees or the investigator