Hayfever, Seasonal Allergic Rhinitis
Conditions
Keywords
Seasonal Allergic Rhinitis, Hayfever
Brief summary
This is a phase 2, randomized, double-blind, placebo-controlled, parallel-group, 2-week, multi-center, dose-range-finding study in male or female patients (12 years and older) with SAR.
Interventions
DRUGBeclomethasone dipropionate HFA Nasal Aerosol
Beclomethasone dipropionate (BDP) Hydrofluoroalkane (HFA) Nasal Aerosol
DRUGPlacebo
HFA Vehicle Aerosol
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
Key Inclusion Criteria: * Male or female patients 12 years of age and 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 patient at increased risk during the study. * A history of SAR to relevant seasonal allergen (tree/grass pollen) for a minimum of two years immediately preceding the study Screening Visit (SV). The SAR 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 be exposed to the allergen and require treatment throughout the entire study period. * A demonstrated sensitivity to relevant tree/grass pollen known to produce SAR through a standard skin prick test. A positive test is defined as a wheal diameter at least 3 mm larger than the control wheal for the skin prick test. Documentation of a positive result within 12 months prior to Screening Visit (SV) is acceptable. * Other criteria apply Key
Exclusion criteria
* 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 physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations, recent nasal biopsy, nasal trauma or surgery, atrophic rhinitis, or rhinitis medicamentosa (all within the last 60 days prior to the SV). * History of a respiratory infection or disorder \[including, but not limited to bronchitis, pneumonia, chronic sinusitis, influenza, severe acute respiratory syndrome (SARS)\] within the 14 days preceding the Screening Visit (SV), or development of a respiratory infection during the Run-in Period. * Use of any prohibited concomitant medications within the prescribed (per protocol) time since the last dosing period prior to the Screening Visit (SV) and/or plans for use during the entire treatment duration. * Other criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period | Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period) | Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the past 12 hours twice daily (AM & PM) using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (sign/symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period | Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period) | Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the 10 minutes prior to the assessment, twice daily (AM & PM) using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of symptom, bothersome but tolerable); 3=severe (symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement. |
| Change From Baseline in Morning Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two-week Treatment Period | Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period) | Change from Baseline in the morning patient-reported instantaneous TNSS. Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the past 10 minutes (prior to the assessment) in the morning on a scale from 0 (mild symptoms) to 3 (severe symptoms). The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement. |
| Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | Baseline and Week 2 | 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. A negative change from Baseline score indicates symptom improvement. |
| Change From Baseline in Morning 24-hour Reflective Ocular Symptom Score Over the Two-week Treatment Period | Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period) | Participants recorded the severity of their symptoms (itching/burning eyes, tearing/watering eyes and redness of eyes) for the past 24 hours each morning using the following scale: 0=absent (no sign/symptoms); 1=mild (sign/symptom present, minimal awareness, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (sign/symptom hard to tolerate, interfere with daily activities or sleeping). The total ocular symptom score (sum of 3 symptom scores) ranges from 0 to 9 (worst symptoms). A negative change from Baseline score indicates symptom improvement. |
| Change From Baseline in Morning 24-hour Reflective Non-nasal Symptom Score Over the Two-week Treatment Period | Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period) | Participants recorded the severity of their symptoms (itching/burning eyes, tearing/watering eyes, redness of eyes and itching of ears or palate) for the past 24 hours each morning using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (symptoms hard to tolerate, interfere with daily activities or sleeping). Total non-nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement. |
Countries
United States
Participant flow
Recruitment details
A total of 685 patients were screened and 635 were enrolled in the study and participated in the Run-in Period. Of the 635 enrolled patients, 487 were randomized to treatment. The study was performed in the spring during tree and grass pollen seasons.
Pre-assignment details
During the 7 - 21 day Run-in Period, patients self-administered a single-blind placebo nasal aerosol once daily in the morning and assessed and recorded their twice daily allergic rhinitis symptoms to determine eligibility for randomization.
Participants by arm
| Arm | Count |
|---|---|
| BDP HFA 80 µg/Day During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily. | 118 |
| BDP HFA 160 µg/Day During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily. | 123 |
| BDP HFA 320 µg/Day During the 2-week double-blind Treatment Period participants self-administered 4 actuations (two per nostril) of 80 µg BDP HFA once daily. | 122 |
| Placebo During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of placebo HFA once daily. | 123 |
| Total | 486 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 6 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 3 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | BDP HFA 80 µg/Day | BDP HFA 160 µg/Day | BDP HFA 320 µg/Day | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 37.6 years STANDARD_DEVIATION 13.86 | 39.8 years STANDARD_DEVIATION 15.26 | 38.5 years STANDARD_DEVIATION 14.74 | 38.2 years STANDARD_DEVIATION 13.95 | 38.5 years STANDARD_DEVIATION 14.45 |
| Race/Ethnicity, Customized Asian | 2 Participants | 5 Participants | 0 Participants | 6 Participants | 13 Participants |
| Race/Ethnicity, Customized Black | 23 Participants | 18 Participants | 22 Participants | 19 Participants | 82 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 14 participants | 10 participants | 17 participants | 15 participants | 56 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 104 participants | 113 participants | 105 participants | 108 participants | 430 participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 92 Participants | 99 Participants | 98 Participants | 97 Participants | 386 Participants |
| Region of Enrollment United States | 118 participants | 123 participants | 122 participants | 123 participants | 486 participants |
| Sex: Female, Male Female | 76 Participants | 86 Participants | 81 Participants | 73 Participants | 316 Participants |
| Sex: Female, Male Male | 42 Participants | 37 Participants | 41 Participants | 50 Participants | 170 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 118 | 3 / 123 | 3 / 122 | 1 / 123 |
| serious Total, serious adverse events | 0 / 118 | 2 / 123 | 0 / 122 | 0 / 123 |
Outcome results
Primary
Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period
Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the past 12 hours twice daily (AM & PM) using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (sign/symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.
Time frame: Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)
Population: The Intent-to-treat population included all randomized patients who received at least one dose of randomized study medication and had at least one post-baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 µg/Day | Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period | -1.88 units on a scale | Standard Error 0.18 |
| BDP HFA 160 µg/Day | Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period | -1.87 units on a scale | Standard Error 0.18 |
| BDP HFA 320 µg/Day | Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period | -2.22 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period | -1.59 units on a scale | Standard Error 0.18 |
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.25595% CI: [-0.8, 0.21]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.25795% CI: [-0.78, 0.21]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.01395% CI: [-1.13, -0.13]Repeated measures ANCOVA
Secondary
Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period
Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the 10 minutes prior to the assessment, twice daily (AM & PM) using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of symptom, bothersome but tolerable); 3=severe (symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.
Time frame: Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)
Population: Intent to treat population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 µg/Day | Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period | -1.77 units on a scale | Standard Error 0.18 |
| BDP HFA 160 µg/Day | Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period | -1.71 units on a scale | Standard Error 0.18 |
| BDP HFA 320 µg/Day | Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period | -2.10 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period | -1.50 units on a scale | Standard Error 0.18 |
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.27895% CI: [-0.77, 0.22]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.38595% CI: [-0.7, 0.27]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.01695% CI: [-1.09, -0.11]Repeated Measures ANCOVA
Secondary
Change From Baseline in Morning 24-hour Reflective Non-nasal Symptom Score Over the Two-week Treatment Period
Participants recorded the severity of their symptoms (itching/burning eyes, tearing/watering eyes, redness of eyes and itching of ears or palate) for the past 24 hours each morning using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (symptoms hard to tolerate, interfere with daily activities or sleeping). Total non-nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.
Time frame: Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)
Population: The non-nasal population included only those participants with adequate non-nasal symptoms during the Run-in Period as defined by a mean daily 24-hour reflective score of 6 or greater for the 24-hour reflective non-nasal symptom score, over the last 7 days of the Run-in Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 µg/Day | Change From Baseline in Morning 24-hour Reflective Non-nasal Symptom Score Over the Two-week Treatment Period | -1.55 units on a scale | Standard Error 0.22 |
| BDP HFA 160 µg/Day | Change From Baseline in Morning 24-hour Reflective Non-nasal Symptom Score Over the Two-week Treatment Period | -1.49 units on a scale | Standard Error 0.22 |
| BDP HFA 320 µg/Day | Change From Baseline in Morning 24-hour Reflective Non-nasal Symptom Score Over the Two-week Treatment Period | -1.91 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in Morning 24-hour Reflective Non-nasal Symptom Score Over the Two-week Treatment Period | -1.51 units on a scale | Standard Error 0.22 |
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.90395% CI: [-0.64, 0.57]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.95295% CI: [-0.58, 0.62]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.18795% CI: [-0.99, 0.19]Repeated measures ANCOVA
Secondary
Change From Baseline in Morning 24-hour Reflective Ocular Symptom Score Over the Two-week Treatment Period
Participants recorded the severity of their symptoms (itching/burning eyes, tearing/watering eyes and redness of eyes) for the past 24 hours each morning using the following scale: 0=absent (no sign/symptoms); 1=mild (sign/symptom present, minimal awareness, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (sign/symptom hard to tolerate, interfere with daily activities or sleeping). The total ocular symptom score (sum of 3 symptom scores) ranges from 0 to 9 (worst symptoms). A negative change from Baseline score indicates symptom improvement.
Time frame: Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)
Population: The ocular population included only those participants with adequate ocular symptoms during the Run-in Period as defined by a mean daily 24-hour reflective score of 4 or greater for the 24-hour reflective ocular symptom score, over the last 7 days of the Run-in Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 µg/Day | Change From Baseline in Morning 24-hour Reflective Ocular Symptom Score Over the Two-week Treatment Period | -1.16 units on a scale | Standard Error 0.16 |
| BDP HFA 160 µg/Day | Change From Baseline in Morning 24-hour Reflective Ocular Symptom Score Over the Two-week Treatment Period | -1.11 units on a scale | Standard Error 0.16 |
| BDP HFA 320 µg/Day | Change From Baseline in Morning 24-hour Reflective Ocular Symptom Score Over the Two-week Treatment Period | -1.46 units on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in Morning 24-hour Reflective Ocular Symptom Score Over the Two-week Treatment Period | -1.17 units on a scale | Standard Error 0.16 |
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.98995% CI: [-0.45, 0.46]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.80895% CI: [-0.39, 0.5]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.19595% CI: [-0.74, 0.15]Repeated measures ANCOVA
Secondary
Change From Baseline in Morning Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two-week Treatment Period
Change from Baseline in the morning patient-reported instantaneous TNSS. Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the past 10 minutes (prior to the assessment) in the morning on a scale from 0 (mild symptoms) to 3 (severe symptoms). The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.
Time frame: Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)
Population: Intent to treat population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 µg/Day | Change From Baseline in Morning Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two-week Treatment Period | -1.76 units on a scale | Standard Error 0.18 |
| BDP HFA 160 µg/Day | Change From Baseline in Morning Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two-week Treatment Period | -1.71 units on a scale | Standard Error 0.18 |
| BDP HFA 320 µg/Day | Change From Baseline in Morning Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two-week Treatment Period | -2.14 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in Morning Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two-week Treatment Period | -1.31 units on a scale | Standard Error 0.18 |
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.08295% CI: [-0.95, 0.06]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.11495% CI: [-0.9, 0.1]Repeated measures ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.00195% CI: [-1.33, -0.33]Repeated measures ANCOVA
Secondary
Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
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. A negative change from Baseline score indicates symptom improvement.
Time frame: Baseline and Week 2
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 the Randomization Visit of 3.0 or greater.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 µg/Day | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.30 units on a scale | Standard Error 0.17 |
| BDP HFA 160 µg/Day | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.33 units on a scale | Standard Error 0.15 |
| BDP HFA 320 µg/Day | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.62 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.22 units on a scale | Standard Error 0.16 |
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.74795% CI: [-0.52, 0.37]ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.60595% CI: [-0.53, 0.31]ANCOVA
Comparison: A priori threshold for statistical significance is p\<0.05.p-value: 0.08395% CI: [-0.84, 0.05]ANCOVA