Back to resultsStudy 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
Primary Purpose
Bilateral Nasal Polyposis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Fluticasone Propionate
Sponsored by
About this trial
This is an interventional treatment trial for Bilateral Nasal Polyposis
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
Sites / Locations
- SC Clinical Research, Inc.
- Kern Allergy and Medical Research, Inc.
- Central California Clinical Research
- Allergy & Asthma Specialists Medical Group
- California Allergy & Asthma Medical Group, Inc.
- Choc PSF, AMC, Division of AA & I
- California Allergy and Asthma Palmdale
- Peninsula Research Associates, Inc.
- California Medical Clinic for Headache
- Asthma & Allergy Associates, P.C.
- Colorado ENT & Allergy
- Colorado Allergy and Asthma Centers, P.C.
- University of South Florida Asthma, Allergy & Immunology
- NU Feinberg School of Medicine Depart. of Otolaryngology-Head & Neck Surgery
- Chicago ENT
- Northeast Medical Research Associates, Inc
- The Center for Pharmaceutical Research, P.C.
- Clinical Research Group of Montana, PLLC
- Coastal Ear, Nose and Throat, LLC
- Montefiore Medical Center
- Cleveland Clinic
- Optimed Research
- Allergy, Asthma & Clinical Research Center
- Vital Prospects Clinical Research Institute
- National Allergy, Asthma & Urticaria Centers of Charleston, P.A.
- AARA Research Center
- Ear Nose and Throat Associates of Texas
- ENTTEX
- EVMS Depart. Of Otolaryngology
- Allergy, Asthma & Sinus Center, S.C.
- Ottawa Allergy Research Corporation
- CHUM Hôtel-Dieu
- Dr. Jaime Del Carpio
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Placebo Comparator
Active Comparator
Active Comparator
Arm Label
OPN-375 100 μg BID
Placebo
OPN-375 200 μg BID
OPN-375 400 μg BID
Arm Description
Double-Blind Treatment Phase: OPN-375 100 μg BID x 16 weeks Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Double-Blind Treatment Phase: OPN-375 200 μg BID x 16 weeks Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Double-Blind Treatment Phase: OPN-375 400 μg BID x 16 weeks Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Outcomes
Primary Outcome Measures
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
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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
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
Mild polyposis: polyps not reaching below the inferior border of the middle turbinate
Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate
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
Secondary Outcome Measures
Congestion/Obstruction Scores (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Change in Rhinorrhea Score (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Facial Pain or Pressure Score (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Hyposmia Score (7-day Instantaneous Morning)
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Sinonasal Outcome Test 22 (SNOT-22) Total Score
SNOT-22 is a subject-completed questionnaire that consists of 22 questions. The questions on the SNOT-22 efficacy evaluation were used to calculate a total score. 22 questions are divided among 4 subscales: Rhinologic (7 questions), Ear/Facial Symptoms (4 questions), Sleep Function (3 questions), and Psychological Issues (6 questions). Each item was rated on the 5-point scale. The total score can range from 0-110, 0 being the best and 110 being the worst.
0: No problem
Very mild problem
Mild or slight problem
Moderate problem
Severe problem
Problem as bad as it can be
MOS Sleep-R Score
The MOS Sleep-R is a brief, self-administered, validated questionnaire designed to measure key aspects of sleep, such as disturbance, adequacy, somnolence, and quantity. The 12-item version with a 4-week recall was used in this study. The score range for the 12-item version is 0 to 100, lower scores indicating better sleep and higher scores indicating worse sleep. The scale yields a Sleep Problem Index and scores on the following 6 subscales: Sleep Disturbance, Snoring, Shortness of Breath or Headache, Sleep Adequacy, Sleep Somnolence, and Sleep Quantity.
Rhinosinusitis Disability Index (RSDI) Total Score
The RSDI is a subject-completed instrument that evaluates the self-perceived impact of disease specific head and neck disorders. The RSDI has 30 items in 3 domains: Physical (11 items), Functional (9 items), and Emotional (10 items). The RSDI scale ranges from 0-120, 0 being better quality of life and less impact of CRS on daily function and 120 being worse quality of life and more impact of CRS on daily function.
SF-36v2 - Mental Component
The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.
SF-36v2 - Physical Component
The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health perceptions. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Patient Global Impression of Change (PGIC) Score
Subject responses to the question: "Since starting the study drug, how would you rate the change in your symptoms?" Percentage includes patients who scored either "very much improved," "much improved," or "minimally improved."
Peak Nasal Inspiratory Flow (PNIF)
The PNIF is an assessment of nasal passage obstruction and was measured using an In-Check portable nasal inspiratory flow meter. To measure PNIF, a mask was placed over the nose during inspiration and inspiratory flow was recorded. Each subject inhaled 3 times and each measurement was recorded. The PNIF value used was the greatest of the 3 results at each time point.
Polyp Grade of 0 in at Least One Nostril
Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. This outcome measured how many patients with a polyp grad of 0 in at least 1 nostril.
0: No polyps
Mild polyposis: polyps not reaching below the inferior border of the middle turbinate
Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate
Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate
Nasal Polyp Surgery Eligilbilty
A subject was considered eligible for surgical intervention if the following conditions were met:
Subject has had moderate symptoms of congestion from nasal polyposis for ≥ 3 months.
Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for ≥ 6 weeks.
Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for ≥ 6 weeks.
Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score ≥ 2 in at least 1 nostril).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01622569
Brief Title
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
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
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
November 19, 2013 (Actual)
Primary Completion Date
August 6, 2015 (Actual)
Study Completion Date
October 1, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Optinose US Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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 OPN-375 (100, 200, and 400 µg bid) 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) entered the study.
Pretreatment phase (single-blind, placebo, run-in): 7 to up 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.
Double-blind treatment phase: 16 weeks duration with 6 scheduled visits starting with Visit 2, Day 1 (baseline) when eligible subjects were randomized by balance allocation to 1 of 4 treatment groups and ending at Visit 7 (Week 16).
Open-label extension phase: 8 weeks duration with 1 scheduled visit (Visit 8 [Week 24]).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bilateral Nasal Polyposis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
323 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OPN-375 100 μg BID
Arm Type
Active Comparator
Arm Description
Double-Blind Treatment Phase: OPN-375 100 μg BID x 16 weeks
Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks
Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Arm Title
OPN-375 200 μg BID
Arm Type
Active Comparator
Arm Description
Double-Blind Treatment Phase: OPN-375 200 μg BID x 16 weeks
Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Arm Title
OPN-375 400 μg BID
Arm Type
Active Comparator
Arm Description
Double-Blind Treatment Phase: OPN-375 400 μg BID x 16 weeks
Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks
Intervention Type
Drug
Intervention Name(s)
Fluticasone Propionate
Other Intervention Name(s)
OPN-375
Intervention Description
Delivered via Optinose Exhalation Delivery System
Primary Outcome Measure Information:
Title
Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms
Description
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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
Time Frame
Baseline, Week 4 of the double-blind treatment phase
Title
Change in Total Polyp Grade
Description
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
Mild polyposis: polyps not reaching below the inferior border of the middle turbinate
Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate
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
Time Frame
Baseline, Week 16 of the double-blind treatment phase
Secondary Outcome Measure Information:
Title
Congestion/Obstruction Scores (7-day Instantaneous Morning)
Description
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Time Frame
Baseline, Week 16 of the double-blind treatment phase
Title
Change in Rhinorrhea Score (7-day Instantaneous Morning)
Description
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Time Frame
Baseline, Week 16 of the double-blind treatment phase
Title
Facial Pain or Pressure Score (7-day Instantaneous Morning)
Description
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Time Frame
Baseline, Week 16 of the double-blind treatment phase
Title
Hyposmia Score (7-day Instantaneous Morning)
Description
Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.
0: None
Mild, symptoms clearly present, but minimal awareness, and easily tolerated
Moderate, definite awareness of symptoms that is bothersome but tolerable
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 16 Visit of the double-blind treatment phase
Time Frame
Baseline, Week 16 of the double-blind treatment phase
Title
Sinonasal Outcome Test 22 (SNOT-22) Total Score
Description
SNOT-22 is a subject-completed questionnaire that consists of 22 questions. The questions on the SNOT-22 efficacy evaluation were used to calculate a total score. 22 questions are divided among 4 subscales: Rhinologic (7 questions), Ear/Facial Symptoms (4 questions), Sleep Function (3 questions), and Psychological Issues (6 questions). Each item was rated on the 5-point scale. The total score can range from 0-110, 0 being the best and 110 being the worst.
0: No problem
Very mild problem
Mild or slight problem
Moderate problem
Severe problem
Problem as bad as it can be
Time Frame
Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Title
MOS Sleep-R Score
Description
The MOS Sleep-R is a brief, self-administered, validated questionnaire designed to measure key aspects of sleep, such as disturbance, adequacy, somnolence, and quantity. The 12-item version with a 4-week recall was used in this study. The score range for the 12-item version is 0 to 100, lower scores indicating better sleep and higher scores indicating worse sleep. The scale yields a Sleep Problem Index and scores on the following 6 subscales: Sleep Disturbance, Snoring, Shortness of Breath or Headache, Sleep Adequacy, Sleep Somnolence, and Sleep Quantity.
Time Frame
Baseline, Week 16 of the double-blind treatment phase
Title
Rhinosinusitis Disability Index (RSDI) Total Score
Description
The RSDI is a subject-completed instrument that evaluates the self-perceived impact of disease specific head and neck disorders. The RSDI has 30 items in 3 domains: Physical (11 items), Functional (9 items), and Emotional (10 items). The RSDI scale ranges from 0-120, 0 being better quality of life and less impact of CRS on daily function and 120 being worse quality of life and more impact of CRS on daily function.
Time Frame
Baseline, Week 16 of the double-blind treatment phase
Title
SF-36v2 - Mental Component
Description
The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Time Frame
Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Title
SF-36v2 - Physical Component
Description
The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health perceptions. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Time Frame
Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Title
Patient Global Impression of Change (PGIC) Score
Description
Subject responses to the question: "Since starting the study drug, how would you rate the change in your symptoms?" Percentage includes patients who scored either "very much improved," "much improved," or "minimally improved."
Time Frame
Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Title
Peak Nasal Inspiratory Flow (PNIF)
Description
The PNIF is an assessment of nasal passage obstruction and was measured using an In-Check portable nasal inspiratory flow meter. To measure PNIF, a mask was placed over the nose during inspiration and inspiratory flow was recorded. Each subject inhaled 3 times and each measurement was recorded. The PNIF value used was the greatest of the 3 results at each time point.
Time Frame
Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label treatment phase
Title
Polyp Grade of 0 in at Least One Nostril
Description
Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. This outcome measured how many patients with a polyp grad of 0 in at least 1 nostril.
0: No polyps
Mild polyposis: polyps not reaching below the inferior border of the middle turbinate
Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate
Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate
Time Frame
Baseline, Week 16 of the double-blind treatment phase, Week 24 of the end of open-label treatment phase
Title
Nasal Polyp Surgery Eligilbilty
Description
A subject was considered eligible for surgical intervention if the following conditions were met:
Subject has had moderate symptoms of congestion from nasal polyposis for ≥ 3 months.
Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for ≥ 6 weeks.
Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for ≥ 6 weeks.
Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score ≥ 2 in at least 1 nostril).
Time Frame
Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
SC Clinical Research, Inc.
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Kern Allergy and Medical Research, Inc.
City
Bakersfield
State/Province
California
ZIP/Postal Code
93301
Country
United States
Facility Name
Central California Clinical Research
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
Allergy & Asthma Specialists Medical Group
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
California Allergy & Asthma Medical Group, Inc.
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Choc PSF, AMC, Division of AA & I
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
California Allergy and Asthma Palmdale
City
Palmdale
State/Province
California
ZIP/Postal Code
93551
Country
United States
Facility Name
Peninsula Research Associates, Inc.
City
Rolling Hills Estates
State/Province
California
ZIP/Postal Code
90274
Country
United States
Facility Name
California Medical Clinic for Headache
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Asthma & Allergy Associates, P.C.
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Colorado ENT & Allergy
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Facility Name
Colorado Allergy and Asthma Centers, P.C.
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
University of South Florida Asthma, Allergy & Immunology
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
NU Feinberg School of Medicine Depart. of Otolaryngology-Head & Neck Surgery
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Chicago ENT
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Facility Name
Northeast Medical Research Associates, Inc
City
North Dartmouth
State/Province
Massachusetts
ZIP/Postal Code
02747
Country
United States
Facility Name
The Center for Pharmaceutical Research, P.C.
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64114
Country
United States
Facility Name
Clinical Research Group of Montana, PLLC
City
Bozeman
State/Province
Montana
ZIP/Postal Code
59718
Country
United States
Facility Name
Coastal Ear, Nose and Throat, LLC
City
Neptune
State/Province
New Jersey
ZIP/Postal Code
07753
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Optimed Research
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Allergy, Asthma & Clinical Research Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73120
Country
United States
Facility Name
Vital Prospects Clinical Research Institute
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
National Allergy, Asthma & Urticaria Centers of Charleston, P.A.
City
North Charleston
State/Province
South Carolina
ZIP/Postal Code
29420
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Ear Nose and Throat Associates of Texas
City
Frisco
State/Province
Texas
ZIP/Postal Code
43235
Country
United States
Facility Name
ENTTEX
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
EVMS Depart. Of Otolaryngology
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Allergy, Asthma & Sinus Center, S.C.
City
Greenfield
State/Province
Wisconsin
ZIP/Postal Code
53228
Country
United States
Facility Name
Ottawa Allergy Research Corporation
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4G2
Country
Canada
Facility Name
CHUM Hôtel-Dieu
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1T8
Country
Canada
Facility Name
Dr. Jaime Del Carpio
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1L5
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
35437059
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. 2022 Apr 18:1455613221088698. doi: 10.1177/01455613221088698. Online ahead of print.
Results Reference
derived
PubMed Identifier
34753535
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.
Results Reference
derived
Learn more about this trial
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
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