Efficacy and Safety Study of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Using a Novel Bi-directional Device

NCT01624662 | Completed Phase 3 Results

• 1 other identifier: OPN-FLU-NP-3102
• Study Type: interventional
• Target: 323
• Locations: 1 country
• Sites: 10

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.

Conditions

Bilateral Nasal Polyposis

Outcome Measures

Primary Outcomes (2)

• Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms

  Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 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 During the single-blind run-in phase and during the 16-week, double-blind treatment phase, an electronic diary was provided to each subject. Subjects reported both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptoms severity over the previous 12 hours) scores for nasal congestion/obstruction symptoms.

  Baseline, Week 4 of the double-blind treatment phase

• Change in Total Polyp Grade

  Determined by a nasal polyp grading scale score (sum of scores from both nasal cavities) measured by nasoendoscopy

  Baseline, Week 16 of the double-blind treatment phase

Secondary Outcomes (14)

• Nasal Congestion/Obstruction Score (7-day Instantaneous Morning)

  Week 16 of the double-blind treatment phase

• Change in Rhinorrhea Score (7-day Instantaneous Morning)

  Baseline, Week 16 of the double-blind treatment phase

• Facial Pain or Pressure Score (7-day Instantaneous Morning)

  Week 16 of the double-blind treatment phase

• Hyposmia Score (7-day Instantaneous Morning)

  Week 16 of the double-blind treatment phase

• Change in Total Nasal Polyp Score

  Baseline, Week 24 of the open-label extension phase

Study Arms (4)

OPN-375 100 mcg

ACTIVE COMPARATOR

Double-Blind Treatment Phase: OPN-375 100 mcg BID x 16 weeks; Open-Label Extension Phase: OPN-375 400 mcg BID x 8 weeks

Drug: Fluticasone propionate

OPN-375 200 mcg

ACTIVE COMPARATOR

Double-Blind Treatment Phase: OPN-375 200 mcg BID x 16 weeks; Open-Label Extension Phase: OPN-375 400 mcg BID x 8 weeks

Drug: Fluticasone propionate

OPN-375 400 mcg

ACTIVE COMPARATOR

Double-Blind Treatment Phase: OPN-375 400 mcg BID x 16 weeks; Open-Label Extension Phase: OPN-375 400 mcg BID x 8 weeks

Drug: Fluticasone propionate

Placebo

PLACEBO COMPARATOR

Double-Blind Treatment Phase: Matched Placebo BID x 16 weeks; Open-Label Extension Phase: OPN-375 400 mcg BID x 8 weeks

Drug: Fluticasone propionate

Interventions

Fluticasone propionate DRUG

Delivered via Optinose Exhalation Delivery System

Also known as: OPN-375

OPN-375 100 mcg; OPN-375 200 mcg; OPN-375 400 mcg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Optinose US Inc.: lead

Study Sites (10)

Bensch Clinical Research LLC

Stockton, California, 95207, United States

Location

Colorado Allergy & Asthma Centers, PC

Centennial, Colorado, 80112, United States

Location

Advanced ENT and Allergy

Louisville, Kentucky, 40207, United States

Location

Institute for Asthma and Allergy

Wheaton, Maryland, 20902, United States

Location

Atlantic Research Center, LLC

Ocean City, New Jersey, 07712, United States

Location

Allergy and Asthma Research Group

Eugene, Oregon, 97401, United States

Location

Baker Allergy, Asthma and Dermatology Research Center, LLC

Lake Oswego, Oregon, 98225, United States

Location

Valley Clinical Research Center

Bethlehem, Pennsylvania, 18020, United States

Location

University of Vermont

Burlington, Vermont, 05405, United States

Location

Bellingham Asthma, Allergy, and Immunology Clinic

Bellingham, Washington, 98225, United States

Location

Related Publications (3)

• 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.

  PMID: 35437059 DERIVED

• 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.

  PMID: 34753535 DERIVED

• 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.

  PMID: 29928924 DERIVED

MeSH Terms

Interventions

Fluticasone

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Vice President Global Clinical Operations & Outsourcing
• Organization: OptiNose

jennifer.carothers@optinose.com

267-364-3508

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2012
• First Posted: June 21, 2012
• Study Start: October 30, 2013
• Primary Completion: May 11, 2015
• Study Completion: July 3, 2015
• Last Updated: December 5, 2018
• Results First Posted: December 5, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

US (10)