Rhinitis, Allergic, Perennial
Conditions
Keywords
Rhinitis, Allergic, Perennial, BDP-HFA, Hay fever, Allergic rhinitis
Brief summary
Subjects with perennial allergic rhinitis will be randomized to 320 mcg of beclomethasone dipropionate (BDP) using a hydrofluoroalkane (HFA) propellant or placebo as a nasal aerosol. The subjects will be followed for safety and efficacy for a period of 30 or 52 weeks. BDP HFA is a steroid which is currently FDA approved for the treatment of asthma. BDP-HFA should be safe and effective as a dry nasal aerosol which may be preferred by some patients.
Interventions
DRUGBeclomethasone dipropionate
Total daily dose of 320 micrograms per day of beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) applied as a nasal aerosol each morning for 30-weeks (or 52-weeks, depending upon investigator site).
Placebo nasal aerosol administered daily for 30-weeks (or 52-weeks, depending upon investigator site).
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, 12 years of age or older as of the Screening Visit (SV) * General good health, and free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the subject at increased risk during the study * A history of PAR to a relevant perennial allergen for a minimum of two years immediately preceding the study Screening Visit (SV). The PAR must have been of sufficient severity to have required treatment (either continuous or intermittent) in the past, and in the investigator's judgment is expected to require treatment throughout the entire study * A demonstrated sensitivity to at least one allergen known to induce PAR through a standard skin prick test. A positive test is defined as a wheal diameter at least 3 mm larger than the diluent control wheal for the skin prick test. Documentation of a positive result 12 months prior to Screening Visit (SV) is acceptable * Other criteria apply
Exclusion criteria
* History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations, recent nasal biopsy, nasal trauma, including nasal piercing, or surgery and atrophic rhinitis or rhinitis medicamentosa (all within the last 60 days prior to Screening Visit \[SV\]) * Participation in any investigational drug study within the 30 days preceding the Screening Visit (SV) or planned participation in another investigational drug study at any time during this study * History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, chronic sinusitis, or influenza within the 14 days preceding the Screening Visit (SV) or development of a respiratory infection during the Run-In Period * Active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of β-agonists and any controller drugs (e.g., theophylline, leukotriene antagonists). History of intermittent use (less than or equal to 3 uses per week) of inhaled short acting beta-agonists prior to the Screening Visit (SV) is acceptable. * Other criteria apply Randomization Criteria * Subject continues to be in general good health, meeting the selection criteria * Subject has a minimum subject-reported reflective TNSS of an average of 5 (out of a possible 12) on the last 7 days during the Run-In Period * The subject-reported scores for rhinorrhea or nasal congestion must be an average of 2 or greater during the last 7 days of the Run-In Period * Each subject must have adequately completed the electronic AR Assessment Diary (failure is defined as missing the diary entry on more than 2 calendar days during the last 7 days of the Run-In Period) * Other criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 30 Weeks | Baseline (Days -6 to 0), Day 1 to Week 30 | Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 24-hours (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 30 Weeks | Baseline (Days -6 to 0), Day 1 to Week 30 | Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 10 minutes (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement. |
| Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 52 Weeks | Baseline (Days -6 to 0), Day 1 to Week 52 | Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 24-hours (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement. |
| Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 52 Weeks | Baseline (Days -6 to 0), Day 1 to Week 52 | Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 10 minutes (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement. |
| Change From Baseline to Week 30 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline | Day 0 (Baseline) and Week 30 | The adult RQLQ has 28 questions in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional). Participants were asked to recall their experiences during the previous week and to give their responses on a 7-point scale (0 = Least severe to 6 = Extremely severe). The overall RQLQ score is the mean of all 28 responses, and ranges from 0 to 7. Week 30 scores were compared to baseline scores. A negative change score indicates improvement. |
| Change From Baseline to Week 52 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline | Day 0 (Baseline) and Week 52 | The adult RQLQ has 28 questions in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional). Participants were asked to recall their experiences during the previous week and to give their responses on a 7-point scale (0 = Least severe to 6 = Extremely severe). The overall RQLQ score is the mean of all 28 responses, and ranges from 0 to 7. Week 52 scores were compared to baseline scores. A negative change score indicates improvement. |
Countries
United States
Participant flow
Recruitment details
A total of 857 patients were screened and 775 patients were enrolled in the study and participated in the Run-in Period. Of the 775 enrolled patients, 529 were randomized to study treatment.
Pre-assignment details
During the 7 to 21 day Run-in Period, participants self-administered a single-blind placebo nasal aerosol once daily in the morning and assessed and recorded their daily seasonal rhinitis symptoms to determine eligibility for randomization.
Participants by arm
| Arm | Count |
|---|---|
| BDP HFA 320 µg/Day During the 30-week (or 52-week, depending upon investigator site) double-blind Treatment Period participants self-administered 4 actuations (two per nostril) of 80 µg beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) once daily each morning. | 414 |
| Placebo During the 30-week (or 52-week, depending upon investigator site) double-blind Treatment Period participants self-administered four actuations (two per nostril) of placebo HFA once daily each morning. | 110 |
| Total | 524 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 3 |
| Overall Study | Lost to Follow-up | 11 | 2 |
| Overall Study | Other | 3 | 0 |
| Overall Study | Pregnancy | 1 | 2 |
| Overall Study | Protocol Violation | 4 | 5 |
| Overall Study | Sponsor requested withdrawal | 3 | 1 |
| Overall Study | Withdrawal by Subject | 44 | 13 |
Baseline characteristics
| Characteristic | BDP HFA 320 µg/Day | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 13.6 | 35.7 years STANDARD_DEVIATION 12.9 | 37.1 years STANDARD_DEVIATION 13.4 |
| Body mass index | 28.8 kg/m^2 STANDARD_DEVIATION 6.7 | 28.4 kg/m^2 STANDARD_DEVIATION 6.7 | 28.7 kg/m^2 STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 12 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 369 Participants | 98 Participants | 467 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 7 participants | 2 participants | 9 participants |
| Race/Ethnicity, Customized Asian | 13 participants | 1 participants | 14 participants |
| Race/Ethnicity, Customized Black or African American | 63 participants | 14 participants | 77 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 341 participants | 97 participants | 438 participants |
| Sex: Female, Male Female | 286 Participants | 66 Participants | 352 Participants |
| Sex: Female, Male Male | 128 Participants | 44 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 216 / 415 | 37 / 111 |
| serious Total, serious adverse events | 8 / 415 | 3 / 111 |
Outcome results
Primary
Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 30 Weeks
Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 24-hours (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement.
Time frame: Baseline (Days -6 to 0), Day 1 to Week 30
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 320 µg/Day | Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 30 Weeks | -3.4 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 30 Weeks | -2.4 units on a scale | Standard Error 0.22 |
p-value: <0.00195% CI: [-1.5, -0.5]ANCOVA
Secondary
Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 30 Weeks
Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 10 minutes (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement.
Time frame: Baseline (Days -6 to 0), Day 1 to Week 30
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 320 µg/Day | Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 30 Weeks | -2.9 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 30 Weeks | -2.0 units on a scale | Standard Error 0.21 |
p-value: <0.00195% CI: [-1.4, -0.5]ANCOVA
Secondary
Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 52 Weeks
Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 10 minutes (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement.
Time frame: Baseline (Days -6 to 0), Day 1 to Week 52
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 320 µg/Day | Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 52 Weeks | -3.1 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Average Subject-Assessed 24-Hour Instantaneous Total Nasal Symptom Score (iTNSS) up to 52 Weeks | -2.0 units on a scale | Standard Error 0.22 |
p-value: <0.00195% CI: [-1.6, -0.6]ANCOVA
Secondary
Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 52 Weeks
Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) in the past 24-hours (prior to the assessment) daily using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (bothersome but tolerable); 3=severe (hard to tolerate, interfere with daily activities). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from baseline score indicates improvement.
Time frame: Baseline (Days -6 to 0), Day 1 to Week 52
Population: Intent to treat population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 320 µg/Day | Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 52 Weeks | -3.7 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline in Average Subject-Assessed 24-Hour Reflective Total Nasal Symptom Score (rTNSS) up to 52 Weeks | -2.6 units on a scale | Standard Error 0.23 |
p-value: <0.00195% CI: [-1.6, -0.6]ANCOVA
Secondary
Change From Baseline to Week 30 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline
The adult RQLQ has 28 questions in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional). Participants were asked to recall their experiences during the previous week and to give their responses on a 7-point scale (0 = Least severe to 6 = Extremely severe). The overall RQLQ score is the mean of all 28 responses, and ranges from 0 to 7. Week 30 scores were compared to baseline scores. A negative change score indicates improvement.
Time frame: Day 0 (Baseline) and Week 30
Population: The RQLQ population included only those participants over the age of 18 years with an impaired quality of life at Baseline as defined by a RQLQ score at Day 0 of 3.0 or greater.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 320 µg/Day | Change From Baseline to Week 30 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline | -2.2 units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline to Week 30 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline | -1.9 units on a scale | Standard Error 0.19 |
p-value: 0.14395% CI: [-0.7, 0.1]ANCOVA
Secondary
Change From Baseline to Week 52 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline
The adult RQLQ has 28 questions in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional). Participants were asked to recall their experiences during the previous week and to give their responses on a 7-point scale (0 = Least severe to 6 = Extremely severe). The overall RQLQ score is the mean of all 28 responses, and ranges from 0 to 7. Week 52 scores were compared to baseline scores. A negative change score indicates improvement.
Time frame: Day 0 (Baseline) and Week 52
Population: The RQLQ population included only those participants over the age of 18 years with an impaired quality of life at Baseline as defined by a RQLQ score at Day 0 of 3.0 or greater.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 320 µg/Day | Change From Baseline to Week 52 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline | -2.0 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline to Week 52 in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in Participants With Impaired Quality of Life at Baseline | -1.5 units on a scale | Standard Error 0.3 |
p-value: 0.1395% CI: [-1.1, 0.1]ANCOVA