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

NCT01622569 | Completed Phase 3 Results

• 1 other identifier: OPN-FLU-NP-3101
• Study Type: interventional
• Target: 323
• Locations: 2 countries
• Sites: 33

Brief 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.

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 The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 4 Visit of the double-blind treatment phase

  Baseline, Week 4 of the double-blind treatment phase

• Change in Total Polyp Grade

  Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. A summary of the changes from baseline to Week 16 in total polyp grade. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate Reduction in total polyp grade (sum of scores from both nasal cavities) at Week 16 of double-blind treatment phase; Included patients with nasal polyps at baseline

  Baseline, Week 16 of the double-blind treatment phase

Secondary Outcomes (13)

• Congestion/Obstruction Scores (7-day Instantaneous Morning)

  Baseline, 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)

  Baseline, Week 16 of the double-blind treatment phase

• Hyposmia Score (7-day Instantaneous Morning)

  Baseline, Week 16 of the double-blind treatment phase

• Sinonasal Outcome Test 22 (SNOT-22) Total Score

  Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase

Study Arms (4)

OPN-375 100 μg BID

ACTIVE COMPARATOR

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

Drug: Fluticasone Propionate

Placebo

PLACEBO COMPARATOR

Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks

Drug: Fluticasone Propionate

OPN-375 200 μg BID

ACTIVE COMPARATOR

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

Drug: Fluticasone Propionate

OPN-375 400 μg BID

ACTIVE COMPARATOR

Double-Blind Treatment Phase: OPN-375 400 μg BID x 16 weeks Open-Label Extension Phase: OPN-375 400 μg 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 μg BID; OPN-375 200 μg BID; OPN-375 400 μg BID; 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 (33)

SC Clinical Research, Inc.

Tucson, Arizona, 85704, United States

Location

Kern Allergy and Medical Research, Inc.

Bakersfield, California, 93301, United States

Location

Central California Clinical Research

Fresno, California, 93720, United States

Location

Allergy & Asthma Specialists Medical Group

Huntington Beach, California, 92647, United States

Location

California Allergy & Asthma Medical Group, Inc.

Los Angeles, California, 90025, United States

Location

Choc PSF, AMC, Division of AA & I

Orange, California, 92868, United States

Location

California Allergy and Asthma Palmdale

Palmdale, California, 93551, United States

Location

Peninsula Research Associates, Inc.

Rolling Hills Estates, California, 90274, United States

Location

California Medical Clinic for Headache

Santa Monica, California, 90404, United States

Location

Asthma & Allergy Associates, P.C.

Colorado Springs, Colorado, 80907, United States

Location

Colorado ENT & Allergy

Colorado Springs, Colorado, 80909, United States

Location

Colorado Allergy and Asthma Centers, P.C.

Denver, Colorado, 80230, United States

Location

University of South Florida Asthma, Allergy & Immunology

Tampa, Florida, 33613, United States

Location

NU Feinberg School of Medicine Depart. of Otolaryngology-Head & Neck Surgery

Chicago, Illinois, 60611, United States

Location

Chicago ENT

Chicago, Illinois, 60657, United States

Location

Northeast Medical Research Associates, Inc

North Dartmouth, Massachusetts, 02747, United States

Location

The Center for Pharmaceutical Research, P.C.

Kansas City, Missouri, 64114, United States

Location

Clinical Research Group of Montana, PLLC

Bozeman, Montana, 59718, United States

Location

Coastal Ear, Nose and Throat, LLC

Neptune City, New Jersey, 07753, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Optimed Research

Columbus, Ohio, 43235, United States

Location

Allergy, Asthma & Clinical Research Center

Oklahoma City, Oklahoma, 73120, United States

Location

Vital Prospects Clinical Research Institute

Tulsa, Oklahoma, 74136, United States

Location

National Allergy, Asthma & Urticaria Centers of Charleston, P.A.

North Charleston, South Carolina, 29420, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

Ear Nose and Throat Associates of Texas

Frisco, Texas, 43235, United States

Location

ENTTEX

Plano, Texas, 75093, United States

Location

EVMS Depart. Of Otolaryngology

Norfolk, Virginia, 23507, United States

Location

Allergy, Asthma & Sinus Center, S.C.

Greenfield, Wisconsin, 53228, United States

Location

Ottawa Allergy Research Corporation

Ottawa, Ontario, K1Y 4G2, Canada

Location

CHUM Hôtel-Dieu

Montreal, Quebec, H2W 1T8, Canada

Location

Dr. Jaime Del Carpio

Montreal, Quebec, H3G 1L5, Canada

Location

Related Publications (2)

• 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

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
• Restriction Type: OTHER
• 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 19, 2012
• Study Start: November 19, 2013
• Primary Completion: August 6, 2015
• Study Completion: October 1, 2015
• Last Updated: December 26, 2018
• Results First Posted: December 5, 2018

Record last verified: 2017-11

Locations

CA (3); US (30)