Rhinitis, Allergic, Seasonal
Conditions
Keywords
Rhinitis, Seasonal Allergic Rhinitis, Fluticasone furoate, Equivalence, Hay fever
Brief summary
This study compared the safety and efficacy of a generic fluticasone furoate (Lek Pharmaceuticals) nasal spray to the reference listed drug in the treatment of seasonal allergic rhinitis. Additionally both the test and the reference formulations were tested for superiority against a placebo nasal spray.
Detailed description
The study was designed as a double-blind, randomized, placebo-controlled, parallel group, multi-site to compare the clinical equivalence of the test formulation of fluticasone furoate, 27.5 mcg/actuation nasal spray (Lek Pharmaceuticals d.d.) with the reference formulation Veramyst® nasal spray (GlaxoSmithKline) in the relief of the signs and symptoms of seasonal allergic rhinitis. Participants who met the inclusion/exclusion criteria entered a 7-day placebo lead-in period. Following this placebo lead-in period, on Day 1 participants who continued to meet eligibility criteria were randomly assigned in a 2:2:1 ratio to one of three treatment groups (Test Product:Reference Product:Placebo) for 14 days of treatment. In all treatment groups, participants were instructed to administer the study drug once daily at approximately the same time each day. A single dose of 110 mcg was 4 actuations, each containing 27.5 mcg per actuation. Patients were instructed to administer the 4 actuations alternating between right and left nostril, such that 2 actuations were not administered back to back to the same nostril.
Interventions
DRUGFluticasone furoate 27.5 mcg/actuation nasal spray (Lek Pharmaceuticals)
Nasal spray administered once daily at a dose of 110 mcg (4 actuations) for 14 days.
DRUGFluticasone furoate (Veramyst®) 27.5 mcg/actuation nasal spray
Nasal spray administered once daily at a dose of 110 mcg (4 actuations) for 14 days.
DRUGPlacebo
Placebo nasal spray administered once daily (4 actuations) for 14 days.
Sponsors
Sandoz
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 non-pregnant, non-lactating female 12 years of age or older with a minimum of 2 years of previous history of seasonal allergic rhinitis to the pollen/allergen in season at the time the study is being conducted. * Signed informed consent (assent) form. * Documented positive allergic skin test to local pollen. * An average score of at least 6 on the reflective Total Nasal Symptom Score (rTNSS) with a minimum score of at least 2 for nasal congestion and at least 4 on the reflective Total Ocular Symptom Score (rTOSS).
Exclusion criteria
* History of asthma that required chronic therapy (with the exception of occasional acute or mild exercise induced asthma). * Some other past and concomitant medical conditions, prohibited medications. * Upper respiratory tract infection or any untreated infections. * Patient has started immunotherapy/changed the dose. * Any known allergy to any of the components of the study nasal spray.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Equivalence: Per-Protocol Population) | Baseline, 14 days | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTNSS patients were asked to look back or reflect on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTNSS - mean post-randomization rTNSS. A positive change from baseline in rTNSS is considered a favorable outcome. |
| PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | Baseline, 14 days | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTNSS patients were asked to look back or reflect on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTNSS - mean post-randomization rTNSS. A positive change from baseline in rTNSS is considered a favorable outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Equivalence: Per-Protocol Population) | Baseline, 14 days | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTOSS patients were asked to look back or reflect on their severity of ocular symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTOSS - mean post-randomization rTOSS. A positive change from baseline is considered a favorable outcome. |
| Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Superiority: Intent-to-Treat Population) | Baseline, 14 days | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTOSS patients were asked to look back or reflect on their severity of ocular symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTOSS - mean post-randomization rTOSS. A positive change from baseline is considered a favorable outcome. |
| Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population) | Baseline, 14 days | Participants were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS participants were asked to evaluate how I feel now regarding their severity of nasal symptoms. The first rating on each day was taken prior to dosing. Participants were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean iTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline iTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTNSS - mean post-randomization iTNSS. A positive change from baseline in iTNSS is considered a favorable outcome. |
| Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Superiority: Intent-to-Treat Population) | Baseline, 14 days | Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTOSS patients were asked to evaluate how I feel now regarding their severity of ocular symptoms. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTOSS - mean post-randomization iTOSS. A positive change from baseline in iTOSS is considered a favorable outcome. |
| Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Equivalence: Per-Protocol Population) | Baseline, 14 days | Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTOSS patients were asked to evaluate how I feel now regarding their severity of ocular symptoms. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTOSS - mean post-randomization iTOSS. A positive change from baseline in iTOSS is considered a favorable outcome. |
| Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population) | Baseline, 14 days | Participants were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS participants were asked to evaluate how I feel now regarding their severity of nasal symptoms. The first rating on each day was taken prior to dosing. Participants were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean iTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline iTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTNSS - mean post-randomization iTNSS. A positive change from baseline in iTNSS is considered a favorable outcome. |
Countries
United States
Participant flow
Recruitment details
Participants took part in 10 investigative sites in 1 country.
Pre-assignment details
Participants who met the inclusion/exclusion criteria entered a 7-day placebo lead-in period. Following this placebo lead-in period, on Day 1 participants who continued to meet eligibility criteria were randomly assigned in a 2:2:1 ratio to one of three treatment groups (Test Product:Reference Product:Placebo).
Participants by arm
| Arm | Count |
|---|---|
| Test Fluticasone furoate 27.5 mcg/actuation nasal spray (Lek Pharmaceuticals) administered once daily at a dose of 110 mcg (4 actuations) for 14 days. | 288 |
| Reference Fluticasone furoate (Veramyst®) 27.5 mcg/actuation nasal spray administered once daily at a dose of 110 mcg (4 actuations) for 14 days. | 292 |
| Placebo Placebo nasal spray administered once daily for 14 days. | 147 |
| Total | 727 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Insufficient therapeutic response | 0 | 0 | 1 |
| Overall Study | Other | 3 | 3 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 |
| Overall Study | Restricted medication for seasonal allergic rhinitis | 0 | 1 | 0 |
| Overall Study | Withdrew consent | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Test | Reference | Placebo | Total |
|---|---|---|---|---|
| Age, Customized < 18 | 17 Participants | 28 Participants | 17 Participants | 62 Participants |
| Age, Customized 18 - 40 | 133 Participants | 122 Participants | 65 Participants | 320 Participants |
| Age, Customized 41 - 64 | 122 Participants | 137 Participants | 59 Participants | 318 Participants |
| Age, Customized 65 - 75 | 15 Participants | 4 Participants | 6 Participants | 25 Participants |
| Age, Customized > 75 | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian / Alaska Native | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Black/African American | 50 Participants | 40 Participants | 19 Participants | 109 Participants |
| Race/Ethnicity, Customized Native Hawaiian / Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 233 Participants | 241 Participants | 126 Participants | 600 Participants |
| Sex: Female, Male Female | 174 Participants | 195 Participants | 91 Participants | 460 Participants |
| Sex: Female, Male Male | 114 Participants | 97 Participants | 56 Participants | 267 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 288 | 0 / 292 | 0 / 147 |
| other Total, other adverse events | 6 / 288 | 4 / 292 | 4 / 147 |
| serious Total, serious adverse events | 0 / 288 | 0 / 292 | 1 / 147 |
Outcome results
Primary
PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Equivalence: Per-Protocol Population)
Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTNSS patients were asked to look back or reflect on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTNSS - mean post-randomization rTNSS. A positive change from baseline in rTNSS is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Per-Protocol population was used in this analysis. To determine equivalence, only the test and reference treatment arms were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Equivalence: Per-Protocol Population) | 2.036 score on scale | Standard Deviation 2.415 |
| Reference | PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Equivalence: Per-Protocol Population) | 1.904 score on scale | Standard Deviation 2.409 |
90% CI: [87.421, 124.21]
Primary
PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population)
Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTNSS patients were asked to look back or reflect on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTNSS - mean post-randomization rTNSS. A positive change from baseline in rTNSS is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Intent-to-Treat Population including participants with valid measurements for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | 2.035 score on scale | Standard Deviation 2.362 |
| Reference | PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | 1.845 score on scale | Standard Deviation 2.378 |
| Placebo | PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | 0.952 score on scale | Standard Deviation 1.842 |
p-value: <0.0001ANCOVA
p-value: 0.0001ANCOVA
Secondary
Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population)
Participants were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS participants were asked to evaluate how I feel now regarding their severity of nasal symptoms. The first rating on each day was taken prior to dosing. Participants were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean iTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline iTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTNSS - mean post-randomization iTNSS. A positive change from baseline in iTNSS is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Per-Protocol population was used in this analysis. To determine equivalence, only the test and reference treatment arms were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population) | 2.017 score on scale | Standard Deviation 2.439 |
| Reference | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population) | 1.854 score on scale | Standard Deviation 2.411 |
90% CI: [89.256, 127.79]
Secondary
Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population)
Participants were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS participants were asked to evaluate how I feel now regarding their severity of nasal symptoms. The first rating on each day was taken prior to dosing. Participants were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean iTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline iTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTNSS - mean post-randomization iTNSS. A positive change from baseline in iTNSS is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Intent-to-Treat Population including participants with valid measurements for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population) | 1.994 score on scale | Standard Deviation 2.398 |
| Reference | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population) | 1.805 score on scale | Standard Deviation 2.398 |
| Placebo | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population) | 0.846 score on scale | Standard Deviation 1.981 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Equivalence: Per-Protocol Population)
Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTOSS patients were asked to evaluate how I feel now regarding their severity of ocular symptoms. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTOSS - mean post-randomization iTOSS. A positive change from baseline in iTOSS is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Per-Protocol population was used in this analysis. To determine equivalence, only the test and reference treatment arms were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Equivalence: Per-Protocol Population) | 1.389 score on scale | Standard Deviation 1.884 |
| Reference | Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Equivalence: Per-Protocol Population) | 1.135 score on scale | Standard Deviation 1.803 |
90% CI: [95.41, 146.583]
Secondary
Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Superiority: Intent-to-Treat Population)
Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTOSS patients were asked to evaluate how I feel now regarding their severity of ocular symptoms. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTOSS - mean post-randomization iTOSS. A positive change from baseline in iTOSS is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Intent-to-Treat Population including participants with valid measurements for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Superiority: Intent-to-Treat Population) | 1.362 score on scale | Standard Deviation 1.851 |
| Reference | Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Superiority: Intent-to-Treat Population) | 1.118 score on scale | Standard Deviation 1.784 |
| Placebo | Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Superiority: Intent-to-Treat Population) | 0.787 score on scale | Standard Deviation 1.563 |
p-value: 0.0018ANCOVA
p-value: 0.0451ANCOVA
Secondary
Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Equivalence: Per-Protocol Population)
Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTOSS patients were asked to look back or reflect on their severity of ocular symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTOSS - mean post-randomization rTOSS. A positive change from baseline is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Per-Protocol population was used in this analysis. To determine equivalence, only the test and reference treatment arms were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Equivalence: Per-Protocol Population) | 1.388 score on scale | Standard Deviation 1.831 |
| Reference | Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Equivalence: Per-Protocol Population) | 1.152 score on scale | Standard Deviation 1.79 |
90% CI: [94.129, 143.949]
Secondary
Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Superiority: Intent-to-Treat Population)
Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTOSS patients were asked to look back or reflect on their severity of ocular symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTOSS - mean post-randomization rTOSS. A positive change from baseline is considered a favorable outcome.
Time frame: Baseline, 14 days
Population: Intent-to-Treat Population including participants with valid measurements for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Superiority: Intent-to-Treat Population) | 1.373 score on scale | Standard Deviation 1.795 |
| Reference | Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Superiority: Intent-to-Treat Population) | 1.128 score on scale | Standard Deviation 1.762 |
| Placebo | Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Superiority: Intent-to-Treat Population) | 0.787 score on scale | Standard Deviation 1.527 |
p-value: 0.0018ANCOVA
p-value: 0.0441ANCOVA