Clinical trial NCT01624662: Efficacy and Safety Study of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Using a Novel Bi-directional Device
Official title: A 16-Week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bilateral Nasal Polyposis
Lead sponsor: Optinose US Inc.
Sponsor class: INDUSTRY
First posted: 2012-06-21
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to compare the efficacy of intranasal administration of 100, 200, and 400 μg twice daily (bid) of fluticasone propionate, delivered by the Optinose device, with matching placebo in subjects with bilateral nasal polyposis and nasal congestion.

Detailed description: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to assess the efficacy and safety of intranasal administration of 3 doses of fluticasone propionate (100, 200, and 400 μg bid), delivered by the Optinose device, in subjects with bilateral nasal polyposis and nasal congestion.

This study consisted of 3 phases. After signing informed consent, subjects who met eligibility criteria at Visit 1 (screening) visit entered the study.

1. Pretreatment phase (single-blind, placebo, run-in): 7 to 14 days duration, to determine disease status eligibility and to ensure the subject was able to comply with study procedures prior to randomization and enrolment in the double-blind treatment phase
2. Double-blind treatment phase: 16 weeks duration with 6 scheduled visits starting with Visit 2 (Day 1) when eligible subjects were randomized by balance allocation to 1 of 4 treatment groups and ending at Visit 7 (Week 16)
3. Open-label extension phase: 8 weeks duration with 1 scheduled visit (Visit 8 \[Week 24\]), during which all subjects received fluticasone propionate 400 mcg BID delivered by the Optinose device

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

Primary outcomes:
measure: Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms
timeFrame: Baseline, Week 4 of the double-blind treatment phase
measure: Change in Total Polyp Grade
timeFrame: Baseline, Week 16 of the double-blind treatment phase
Secondary outcomes:
measure: Nasal Congestion/Obstruction Score (7-day Instantaneous Morning)
timeFrame: Week 16 of the double-blind treatment phase
measure: Change in Rhinorrhea Score (7-day Instantaneous Morning)
timeFrame: Baseline, Week 16 of the double-blind treatment phase
measure: Facial Pain or Pressure Score (7-day Instantaneous Morning)
timeFrame: Week 16 of the double-blind treatment phase
measure: Hyposmia Score (7-day Instantaneous Morning)
timeFrame: Week 16 of the double-blind treatment phase
measure: Change in Total Nasal Polyp Score
timeFrame: Baseline, Week 24 of the open-label extension phase
measure: Polyp Grade of 0 in at Least One Nostril
timeFrame: Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase
measure: Sinonasal Outcome Test 22 (SNOT-22) Total Score
timeFrame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase
measure: MOS Sleep-R Score
timeFrame: Baseline, Week 16 of the double-blind treatment phase
measure: Rhinosinusitis Disability Index (RSDI) Total Score
timeFrame: Baseline, Week 16 of the double-blind treatment phase
measure: SF-36v2 - Mental Component
timeFrame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase
measure: SF-36v2 - Physical Component
timeFrame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase
measure: Number of Participants in Each Category of PGIC
timeFrame: Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase
measure: Number of Participants Eligible for Nasal Polyp Surgery
timeFrame: Week 16 of the double-blind treatment phase; Week 24 of the open-label extension phase
measure: Peak Nasal Inspiratory Flow (PNIF)
timeFrame: Week 16 of the double-blind treatment phase; Week 24 of the open-label extension phase
Other outcomes:
Locations:
city: Stockton
country: United States
facility: Bensch Clinical Research LLC
state: California
city: Centennial
country: United States
facility: Colorado Allergy & Asthma Centers, PC
state: Colorado
city: Louisville
country: United States
facility: Advanced ENT and Allergy
state: Kentucky
city: Wheaton
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
city: Ocean City
country: United States
facility: Atlantic Research Center, LLC
state: New Jersey
city: Eugene
country: United States
facility: Allergy and Asthma Research Group
state: Oregon
city: Lake Oswego
country: United States
facility: Baker Allergy, Asthma and Dermatology Research Center, LLC
state: Oregon
city: Bethlehem
country: United States
facility: Valley Clinical Research Center
state: Pennsylvania
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Bellingham
country: United States
facility: Bellingham Asthma, Allergy, and Immunology Clinic
state: Washington
Study officials:
References:
citation: Ow RA, McGinnis JP 2nd, Sacks HJ, Mehle ME. The Effect of EDS-FLU on Objective and Patient-Reported Subjective Outcomes for Patients with Chronic Rhinosinusitis with Nasal Polyps. Ear Nose Throat J. 2025 Feb;104(2):93-101. doi: 10.1177/01455613221088698. Epub 2022 Apr 18.
citation: Skoner DP, Meltzer EO, Skoner J, Sacks HJ, Lumry WR. Evaluation of the ocular safety associated with the exhalation delivery system with fluticasone. Allergy Asthma Proc. 2022 Jan 9;43(1):70-77. doi: 10.2500/aap.2022.43.210096. Epub 2021 Nov 9.
citation: Leopold DA, Elkayam D, Messina JC, Kosik-Gonzalez C, Djupesland PG, Mahmoud RA. NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis. J Allergy Clin Immunol. 2019 Jan;143(1):126-134.e5. doi: 10.1016/j.jaci.2018.06.010. Epub 2018 Jun 19.