OPN-375 Efficacy and Safety in Adolescents With Bilateral Nasal Polyps
Primary Purpose
Bilateral Nasal Polyposis
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
OPN-375
Sponsored by
About this trial
This is an interventional treatment trial for Bilateral Nasal Polyposis
Eligibility Criteria
Inclusion Criteria:
- Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening).
Female subjects, if sexually active, must:
- be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g., 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, tubal ligation, or otherwise be incapable of pregnancy), or
- or agree to abstinence.
- Ability to read and speak English
- All female subjects not documented to be infertile (e.g., infertility due to congenital abnormality or surgical sterilization) must have a negative serum or urine beta-human chorionic gonadotropin (β-hCG) at Visit 1 (Screening) and a negative urine pregnancy test at the Visit 2 (Day 1/Randomization/Baseline)
- Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal cavities as determined by a nasal polyp grading scale score measured by nasoendoscopy at Visit 1 (Screening)
- Must report at least mild symptoms of nasal congestion/obstruction as demonstrated by an average morning nasal congestion/obstruction score of at least 1.0 over the last 7 days of the run-in period (Subjects not meeting this inclusion criterion may be re-screened once after at least 4 weeks.)
- Subjects with comorbid asthma must be stable, defined as no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Subjects who received inhaled corticosteroids are required to be on no more than a moderate dosage regimen as defined by 2005 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening) and to be expected to remain on it throughout the study. Visit 1 (Screening)
- Must be able to cease treatment with intranasal medications including, but not limited to, intranasal oxymetazoline or any other decongestants, intranasal antihistamines, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium bromide, as well as inhaled corticosteroids (except permitted doses listed above for asthma) at Visit 1 (Screening). (Note: intranasal antibiotics and saline are permissible)
- If taking oral antihistamines, must be on a stable regimen for at least 2 weeks prior to the Visit 1 (Screening), and agree to not change the dose of these medications until after Visit 3 (Week 4) of the study.
- Subject (with assistance from parent or legal guardian if needed) must demonstrate the ability to correctly complete the daily diary during the run-in period to be eligible for randomization.
- Must demonstrate correct use of the demo exhalation delivery system (EDS).
- Must be capable, in the opinion of the investigator, of providing assent and the appropriate parent(s) or guardian must provide an informed consent to participate in the study.
Exclusion Criteria:
- Pregnancy or lactation
- Has a history of cystic fibrosis
- Have used XHANCE® (fluticasone propionate) nasal spray within the past 2 months
- Inability to achieve bilateral nasal airflow for any reason, including nasal septum deviation
- Inability to examine both nasal cavities for any reason, including severe nasal septum deviation
- Have history of nasal septum erosion, ulceration or perforation or evidence of such lesion on Visit 1 (Screening) nasal examination/nasoendoscopy
- Other significant nasal pathology or abnormal anatomy
- Has had any episode of epistaxis with frank bleeding in the 3 months before Visit 1 (Screening)
- History of more than 5 sinus or nasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime) Visit 1 (Screening)
- Have had any surgery on the nasal septum
- History of sinus or nasal surgery within 6 months before Visit 1 (Screening)
- History of any surgical procedure that prevents the ability to accurately to diagnose or grade polyps if the subject requires nasoendoscopy
- Current, ongoing rhinitis medicamentosa (rebound rhinitis)
- Have significant oral structural abnormalities (e.g., a cleft palate)
- History of Churg-Strauss syndrome or dyskinetic ciliary syndromes
- Purulent nasal infection (recent fever or symptoms of lethargy), acute sinusitis, or upper respiratory tract infection within 2 weeks before Visit 1 (Screening). Potential subjects presenting with one of these infections may be rescreened after 4 weeks
- Have an allergy, hypersensitivity, or contraindication to corticosteroids or steroids
- Have an allergy or hypersensitivity to any excipients in study drug
- Exposure to any glucocorticoid treatment with potential for systemic effects (e.g., oral or parenteral steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma
- Currently receiving Nucala (mepolizumab), Cinquair (reslizumab), Dupixent (dupilumab), or Omalizumab (Xolair®) (note patients should not be removed from their therapy for the sole purpose of study participation)
- Have nasal or oral candidiasis
- Have taken a potent CYP3A4-inhibitor within 14 days before Visit 1 (Screening)
- Any serious or unstable concurrent disease, psychiatric disorder, or any significant concomitant medical 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, or pose a specific risk to the subject due to study participation
- History or current diagnosis of glaucoma or ocular hypertension (intraocular pressure >21 mmHg)
- History of intraocular pressure elevation on any form of steroid therapy
- Current diagnosis of the presence (in either eye) of a cataract of Grade 1 or greater as defined on the Eye Examination Worksheet OR, less than a Grade 1 cataract with associated visual impairment
- A recent (within 1 year of Visit 1 (Screening) clinically significant history of drug or alcohol use, abuse, or dependence)
- Positive urine drug screen at Visit 1 (Screening) for stimulants, opioids, or cocaine
- Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
- Parents, guardian or caregivers of the subject who are 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
- Clinical Research Center of AlabamaRecruiting
- Arizona Allergy and Immunology ResearchRecruiting
- San Tan Allergy & AsthmaRecruiting
- Kern ResearchRecruiting
- Central California Clinical ResearchRecruiting
- Children's Hospital of Orange CountyRecruiting
- Allergy and Asthma ConsultantsRecruiting
- Sacramento ENTRecruiting
- Children's Hospital ColoradoRecruiting
- Yale School of Medicine, Section of OtolaryngologyRecruiting
- Nemours Children's Specialty CareRecruiting
- Children's Healthcare of AtlantaRecruiting
- Rush University Medical Center - Department of OtorhinolaryngologyRecruiting
- Chicago ENTRecruiting
- Kentuckiana ENTRecruiting
- Ochsner Medical Center, Otorhinolaryngology DepartmentRecruiting
- Children's MinnesotaRecruiting
- University of Missouri Medical CenterRecruiting
- University of RochesterRecruiting
- Allergy Asthma & Immunology Research InstituteRecruiting
- Allergy, Asthma & Clinical Research CenterRecruiting
- Vital Prospects Clinical Research Institute, P.C.Recruiting
- MUSC Department of Otolaryngology, Head and Neck SurgeryRecruiting
- Carolina ENTRecruiting
- STAAMP ResearchRecruiting
- University of UtahRecruiting
- Eastern Virginia Medical School - OtolaryngologyRecruiting
- Spokane ENTRecruiting
- West Virginia UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
OPN-375 186 μg BID
Placebo
Arm Description
Double-Blind Treatment Phase: OPN-375 186 μg BID x 16 weeks Open-Label Extension Phase: OPN-375 186 μg BID x 12 weeks
Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks
Outcomes
Primary Outcome Measures
Change in nasal congestion/obstruction symptoms (mild, moderate, severe) at the end of Week 4
Change in nasal congestion/obstruction symptoms at the end of Week 4 measured by the 7-day average instantaneous morning (AM) diary symptom scores (ADS7-IA). The nasal symptom scale is what is used to score the nasal congestion/obstruction score, which is recorded in the diary. Nasal symptom scale is graded on a scale of 0=no symptom, 1=mild symptom, 2=moderate symptom, 3=severe symptom.
Mean change from baseline at Week 16 in total polyp grade
Change in total polyp grade (sum of scores from both nasal cavities) at Week 16 as determined by a nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Secondary Outcome Measures
Change in bilateral polyp grade over time
nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Percentage of subjects with a ≥1 point improvement in polyp grade
nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Percentage of subject with a grade of 0 on at least one side of the nose
nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Change in diary symptom scores for the symptoms of nasal congestion/obstruction, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Change in diary symptom scores for the symptoms of rhinorrhea, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Change in diary symptom scores for the symptoms of facial pain or pressure, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Change in diary symptom scores for the sense of smell, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Sense of smell will be scored on a scale from 0 (normal) to 3 (absent, no sense of smell)
The proportions of subjects who have reductions in the AM and PM, instantaneous and reflective, average nasal congestion/obstruction symptom scores by 0.5 or more points from baseline to the end of the double-blind treatment phase
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Subjects will assess their global impression of change since starting the study drug using the PGIC scale
Subject global impression of change will be assessed using a subject-completed PGIC scale, with a single question rated from 1=very much improved to 7=very much worse
Subjects will assess their change in quality of life since starting the study drug using the quality of life questionnaire (SN-5).
Quality of life assessment using the SN-5 Questionnaire, a subject/parent-completed questionnaire that consists of 5 specific symptoms-related questions (answered on a 7-point Likert scale on the frequency of symptoms, 1=none of the time, 7=all of the time), and 1 general overall quality of life question (answered on a visual analog scale from 0 to 10, worst to best).
Proportion of subjects eligible for surgical intervention (independent of actual surgery performed)
The assessment criteria are as follows:
Subject has had moderate symptoms of congestion from nasal polyposis for at least 3 months.
Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for at least 6 weeks.
Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for at least 6 weeks.
Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score > 2 in at least 1 nostril). Also assess each subject's eligibility for surgery based on specific of criteria (see Section 12) independent of whether the subject actually undergoes surgery.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03747458
Brief Title
OPN-375 Efficacy and Safety in Adolescents With Bilateral Nasal Polyps
Official Title
16-Week Randomized Double-Blind Placebo Controlled Parallel-Group Multicenter Study Evaluating the Efficacy and Safety of OPN-375 186 μg Twice a Day in Adolescents With Bilateral Nasal Polyps Followed With 12-Week Open-Label Treatment Phase
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 31, 2018 (Actual)
Primary Completion Date
March 2026 (Anticipated)
Study Completion Date
March 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Optinose US Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a 16-Week Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of OPN-375 186 μg Twice a Day (BID) in Adolescents with Bilateral Nasal Polyps followed by a 12-Week Open-Label Treatment Phase. The total planned number of subjects is approximately 120 adolescents (12-17 years of age) who will be randomly assigned to receive 1 of 2 study treatments using a 2:1 ratio (OPN-375 186 μg: Placebo). For the PK sub-study, up to 14 subjects will be enrolled to obtain 10 completers.
Detailed Description
The primary objective of this study is to evaluate the efficacy of intranasal administration of OPN-375 186 μg Twice a Day (BID) versus placebo in adolescents with bilateral nasal polyposis and nasal congestion by analyzing the reduction of nasal congestion/obstruction symptoms at the end of Week 4 measured by the 7-day average instantaneous morning diary symptom scores and the reduction in total polyp grade at Week 16 as determined by a nasal polyp grading scale score measured using a 0 to 6 point severity grading scale.
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
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
OPN-375 186 μg BID
Arm Type
Active Comparator
Arm Description
Double-Blind Treatment Phase: OPN-375 186 μg BID x 16 weeks
Open-Label Extension Phase: OPN-375 186 μg BID x 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks
Intervention Type
Drug
Intervention Name(s)
OPN-375
Intervention Description
OPN-375, BID
Primary Outcome Measure Information:
Title
Change in nasal congestion/obstruction symptoms (mild, moderate, severe) at the end of Week 4
Description
Change in nasal congestion/obstruction symptoms at the end of Week 4 measured by the 7-day average instantaneous morning (AM) diary symptom scores (ADS7-IA). The nasal symptom scale is what is used to score the nasal congestion/obstruction score, which is recorded in the diary. Nasal symptom scale is graded on a scale of 0=no symptom, 1=mild symptom, 2=moderate symptom, 3=severe symptom.
Time Frame
4 Weeks
Title
Mean change from baseline at Week 16 in total polyp grade
Description
Change in total polyp grade (sum of scores from both nasal cavities) at Week 16 as determined by a nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Time Frame
16 Weeks
Secondary Outcome Measure Information:
Title
Change in bilateral polyp grade over time
Description
nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Time Frame
16 Weeks
Title
Percentage of subjects with a ≥1 point improvement in polyp grade
Description
nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Time Frame
16 Weeks
Title
Percentage of subject with a grade of 0 on at least one side of the nose
Description
nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Time Frame
16 Weeks
Title
Change in diary symptom scores for the symptoms of nasal congestion/obstruction, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Description
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Time Frame
16 Weeks
Title
Change in diary symptom scores for the symptoms of rhinorrhea, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Description
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Time Frame
16 Weeks
Title
Change in diary symptom scores for the symptoms of facial pain or pressure, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Description
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Time Frame
16 Weeks
Title
Change in diary symptom scores for the sense of smell, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Description
Sense of smell will be scored on a scale from 0 (normal) to 3 (absent, no sense of smell)
Time Frame
16 Weeks
Title
The proportions of subjects who have reductions in the AM and PM, instantaneous and reflective, average nasal congestion/obstruction symptom scores by 0.5 or more points from baseline to the end of the double-blind treatment phase
Description
The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Time Frame
16 Weeks
Title
Subjects will assess their global impression of change since starting the study drug using the PGIC scale
Description
Subject global impression of change will be assessed using a subject-completed PGIC scale, with a single question rated from 1=very much improved to 7=very much worse
Time Frame
16 Weeks
Title
Subjects will assess their change in quality of life since starting the study drug using the quality of life questionnaire (SN-5).
Description
Quality of life assessment using the SN-5 Questionnaire, a subject/parent-completed questionnaire that consists of 5 specific symptoms-related questions (answered on a 7-point Likert scale on the frequency of symptoms, 1=none of the time, 7=all of the time), and 1 general overall quality of life question (answered on a visual analog scale from 0 to 10, worst to best).
Time Frame
16 Weeks
Title
Proportion of subjects eligible for surgical intervention (independent of actual surgery performed)
Description
The assessment criteria are as follows:
Subject has had moderate symptoms of congestion from nasal polyposis for at least 3 months.
Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for at least 6 weeks.
Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for at least 6 weeks.
Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score > 2 in at least 1 nostril). Also assess each subject's eligibility for surgery based on specific of criteria (see Section 12) independent of whether the subject actually undergoes surgery.
Time Frame
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
Other Pre-specified Outcome Measures:
Title
Assessment of safety from physical examination-measuring weight
Description
Assessment of safety from physical examination-weight measured in kg or lb
Time Frame
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
Title
Assessment of safety from physical examination-measuring height
Description
Assessment of safety from physical examination-height measured in cm or in
Time Frame
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
Title
Assessment of safety by recording the severity of AEs
Description
Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe
Time Frame
16 Weeks
Title
Assessment of safety by nasal examination
Description
Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum. If present, the nostril location is also recorded, along with severity, and if there is any relation to an injury or trauma
Time Frame
16 Weeks
Title
Assessment of safety by ocular examination-visual acuity
Description
Assessment of safety by performing visual acuity test assessment using eye chart. Separate recording for each eye in the form of a fraction, 20/...
Time Frame
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
Title
Assessment of safety by ocular examination-Intraocular Pressure
Description
Assessment of safety by averaging intraocular pressure measurement of 2 or 3 measurements to determine if it is >21mmHg
Time Frame
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
Title
Assessment of safety by ocular examination-Cataract Evaluation
Description
Cataracts should be again assessed present or absent, If cataract is diagnosed, cataract type per localization should be specified and cataract should be graded 1=mild, 2=moderate, 3=pronounced, 4=severe
Time Frame
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
Title
Assessment of safety measuring vital signs (blood pressure)
Description
Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)
Time Frame
16 Weeks
Title
Assessment of safety measuring vital signs (pulse)
Description
measure pulse in beats per minute (bpm)
Time Frame
16 Weeks
Title
Assessment for safety from the collection of information for concomitant medications usage
Time Frame
16 Weeks
Title
Assessment of pharmacokinetics - AUC(0-t) (pg*hr/mL)
Description
PK Laboratory to determine the concentrations of fluticasone propionate [AUC(0-t) (pg*hr/mL) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose.
Time Frame
8 hours, 1 to 2 weeks before randomization
Title
Assessment of pharmacokinetics - AUC(0-∞) (pg*hr/mL)
Description
PK Laboratory to determine the concentrations of fluticasone propionate [AUC(0-∞) (pg*hr/mL) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose.
Time Frame
8 hours, 1 to 2 weeks before randomization
Title
Assessment of pharmacokinetics - AUCex (%)
Description
PK Laboratory to determine the concentrations of fluticasone propionate [AUCex (%) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose.
Time Frame
8 hours, 1 to 2 weeks before randomization
Title
Assessment of pharmacokinetics - Cmax (pg/mL)
Description
PK Laboratory to determine the concentrations of fluticasone propionate [Cmax (pg/mL) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose.
Time Frame
8 hours, 1 to 2 weeks before randomization
Title
Assessment of pharmacokinetics - tmax (h)
Description
PK Laboratory to determine the concentrations of fluticasone propionate [tmax (h) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose.
Time Frame
8 hours, 1 to 2 weeks before randomization
Title
Assessment of pharmacokinetics - t1/2 (h)
Description
PK Laboratory to determine the concentrations of fluticasone propionate [t1/2 (h) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose.
Time Frame
8 hours, 1 to 2 weeks before randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening).
Female subjects, if sexually active, must:
be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g., 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, tubal ligation, or otherwise be incapable of pregnancy), or
or agree to abstinence.
Ability to read and speak English
All female subjects not documented to be infertile (e.g., infertility due to congenital abnormality or surgical sterilization) must have a negative serum or urine beta-human chorionic gonadotropin (β-hCG) at Visit 1 (Screening) and a negative urine pregnancy test at the Visit 2 (Day 1/Randomization/Baseline)
Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal cavities as determined by a nasal polyp grading scale score measured by nasoendoscopy at Visit 1 (Screening)
Must report at least mild symptoms of nasal congestion/obstruction as demonstrated by an average morning nasal congestion/obstruction score of at least 1.0 over the last 7 days of the run-in period (Subjects not meeting this inclusion criterion may be re-screened once after at least 4 weeks.)
Subjects with comorbid asthma must be stable, defined as no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Subjects who received inhaled corticosteroids are required to be on no more than a moderate dosage regimen as defined by 2005 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening) and to be expected to remain on it throughout the study. Visit 1 (Screening)
Must be able to cease treatment with intranasal medications including, but not limited to, intranasal oxymetazoline or any other decongestants, intranasal antihistamines, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium bromide, as well as inhaled corticosteroids (except permitted doses listed above for asthma) at Visit 1 (Screening). (Note: intranasal antibiotics and saline are permissible)
If taking oral antihistamines, must be on a stable regimen for at least 2 weeks prior to the Visit 1 (Screening), and agree to not change the dose of these medications until after Visit 3 (Week 4) of the study.
Subject (with assistance from parent or legal guardian if needed) must demonstrate the ability to correctly complete the daily diary during the run-in period to be eligible for randomization.
Must demonstrate correct use of the demo exhalation delivery system (EDS).
Must be capable, in the opinion of the investigator, of providing assent and the appropriate parent(s) or guardian must provide an informed consent to participate in the study.
Exclusion Criteria:
Pregnancy or lactation
Has a history of cystic fibrosis
Have used XHANCE® (fluticasone propionate) nasal spray within the past 2 months
Inability to achieve bilateral nasal airflow for any reason, including nasal septum deviation
Inability to examine both nasal cavities for any reason, including severe nasal septum deviation
Have history of nasal septum erosion, ulceration or perforation or evidence of such lesion on Visit 1 (Screening) nasal examination/nasoendoscopy
Other significant nasal pathology or abnormal anatomy
Has had any episode of epistaxis with frank bleeding in the 3 months before Visit 1 (Screening)
History of more than 5 sinus or nasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime) Visit 1 (Screening)
Have had any surgery on the nasal septum
History of sinus or nasal surgery within 6 months before Visit 1 (Screening)
History of any surgical procedure that prevents the ability to accurately to diagnose or grade polyps if the subject requires nasoendoscopy
Current, ongoing rhinitis medicamentosa (rebound rhinitis)
Have significant oral structural abnormalities (e.g., a cleft palate)
History of Churg-Strauss syndrome or dyskinetic ciliary syndromes
Purulent nasal infection (recent fever or symptoms of lethargy), acute sinusitis, or upper respiratory tract infection within 2 weeks before Visit 1 (Screening). Potential subjects presenting with one of these infections may be rescreened after 4 weeks
Have an allergy, hypersensitivity, or contraindication to corticosteroids or steroids
Have an allergy or hypersensitivity to any excipients in study drug
Exposure to any glucocorticoid treatment with potential for systemic effects (e.g., oral or parenteral steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma
Currently receiving Nucala (mepolizumab), Cinquair (reslizumab), Dupixent (dupilumab), or Omalizumab (Xolair®) (note patients should not be removed from their therapy for the sole purpose of study participation)
Have nasal or oral candidiasis
Have taken a potent CYP3A4-inhibitor within 14 days before Visit 1 (Screening)
Any serious or unstable concurrent disease, psychiatric disorder, or any significant concomitant medical 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, or pose a specific risk to the subject due to study participation
History or current diagnosis of glaucoma or ocular hypertension (intraocular pressure >21 mmHg)
History of intraocular pressure elevation on any form of steroid therapy
Current diagnosis of the presence (in either eye) of a cataract of Grade 1 or greater as defined on the Eye Examination Worksheet OR, less than a Grade 1 cataract with associated visual impairment
A recent (within 1 year of Visit 1 (Screening) clinically significant history of drug or alcohol use, abuse, or dependence)
Positive urine drug screen at Visit 1 (Screening) for stimulants, opioids, or cocaine
Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
Parents, guardian or caregivers of the subject who are 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kim Koob
Phone
215-485-1465
Email
kim.koob@optinose.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kim Koob
Organizational Affiliation
Optinose US Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
John Messina
Organizational Affiliation
Optinose US Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Clinical Research Center of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beth Hagerty
Phone
205-209-4130
Email
bhagerty@alabamaallergy.com
Facility Name
Arizona Allergy and Immunology Research
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marguerite Abrahamson
Phone
480-626-6600
Email
mabrahamson@santanallergy.com
Facility Name
San Tan Allergy & Asthma
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marguerite Abrahamson
Phone
480-626-6600
Email
mabrahamson@santanallergy.com
Facility Name
Kern Research
City
Bakersfield
State/Province
California
ZIP/Postal Code
93301
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristy Walker
Phone
661-864-7710
Email
kern4reserach@aol.com
Facility Name
Central California Clinical Research
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Latisha Richardson
Phone
559-432-3303
Ext
229
Email
lrichardson@ccent.com
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Rodriguez
Phone
714-509-3344
Email
Eric.Rodriguez@choc.org
Facility Name
Allergy and Asthma Consultants
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sherry Lipson
Phone
650-216-6111
Email
Sherry.lipsonallergy@gmail.com
Facility Name
Sacramento ENT
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rose Khalatyan
Phone
916-786-3399
Ext
1101
Email
vkhalatyan@sacent.com
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jordyn Dinwiddie
Phone
702-777-5841
Email
jordyn.dinwiddie@childrenscolorado.org
Facility Name
Yale School of Medicine, Section of Otolaryngology
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sherrie Bitterman
Phone
203-584-8404
Email
sherrie.bitterman@yale.edu
Facility Name
Nemours Children's Specialty Care
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Linda Wheeler
Phone
904-697-3015
Email
linda.wheeler@nemours.org
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric hoar
Phone
404-785-1376
Email
eric.hoar@choa.org
Facility Name
Rush University Medical Center - Department of Otorhinolaryngology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mahendra Shah
Phone
312-942-9967
Email
mahendrakumar_shah@rush.edu
Facility Name
Chicago ENT
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Ninos
Phone
773-289-1823
Email
njoseph@chicagoent.com
Facility Name
Kentuckiana ENT
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tracie Bland
Phone
502-583-9425
Email
tbland@kentuckianaent.com
Facility Name
Ochsner Medical Center, Otorhinolaryngology Department
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nabami Malekera
Phone
504-842-6011
Email
carine.malekera@ochsner.org
Facility Name
Children's Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hanan Zavala
Phone
612-813-7131
Email
hanan.zavala@childrensmn.org
Facility Name
University of Missouri Medical Center
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Schneider
Phone
573-882-2549
Email
schneiderri@health.missouri.edu
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Allen
Phone
585-275-1186
Email
paul_allen@urmc.rochester.edu
Facility Name
Allergy Asthma & Immunology Research Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alison Mathews
Phone
704-910-1402
Ext
350
Email
alisonm@aairofcharlotte.com
Facility Name
Allergy, Asthma & Clinical Research Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73120
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anika Nahar
Phone
405-286-9431
Email
anika@mtarpay.com
Facility Name
Vital Prospects Clinical Research Institute, P.C.
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rylee Mendez
Phone
918-392-4550
Email
rylee.mendez@aaicenter.net
Facility Name
MUSC Department of Otolaryngology, Head and Neck Surgery
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shaun Nguyen
Phone
843-792-1356
Email
nguyensh@musc.edu
Facility Name
Carolina ENT
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simone Ansley
Phone
803-536-5511
Email
sansley700@gmail.com
Facility Name
STAAMP Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlos Rodriguez
Phone
210-451-9911
Email
crc@staampallergy.com
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Carricaburu
Phone
801-581-3363
Email
martin.carricaburu@hsc.utah.edu
Facility Name
Eastern Virginia Medical School - Otolaryngology
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Stone
Phone
757-388-6238
Email
stonelj@evms.edu
Facility Name
Spokane ENT
City
Spokane Valley
State/Province
Washington
ZIP/Postal Code
99216
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christi Witte
Phone
509-496-2782
Email
Christi@principleresearchsolutions.com
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aimie Jones
Phone
304-598-6135
Email
Jonesai@wvumedicine.org
12. IPD Sharing Statement
Learn more about this trial
OPN-375 Efficacy and Safety in Adolescents With Bilateral Nasal Polyps
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