Rhinitis, Allergic, Seasonal
Conditions
Keywords
Rhinitis, Seasonal Allergic Rhinitis, Mometasone Furoate, Equivalence, Hay fever
Brief summary
This study compared the efficacy and safety of a generic mometasone 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 mometasone furoate monohydrate, 50 mcg/actuation nasal spray (Lek Pharmaceuticals d.d.) with the reference formulation Nasonex® nasal spray (Schering) 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 200 mcg was 4 actuations, each containing 50 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
DRUGMometasone furoate 50 mcg/actuation nasal spray (Lek Pharmaceuticals)
Mometasone nasal spray administered once daily at a dose of 200 mcg (4 actuations) for 14 days.
DRUGMometasone furoate (Nasonex®) 50 mcg/actuation nasal spray
Mometasone nasal spray administered once daily at a dose of 200 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 form. For patients under the age of majority the parent or legal guardian should sign the consent form and the child will be required to sign a patient assent form. * Documented positive allergic skin test to local pollen, performed within the past 12 months. * A 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 a minimum score of at least 2 for one of the remaining 3 symptoms.
Exclusion criteria
* Females who are pregnant, lactating or likely to become pregnant during the study. * History of asthma over the previous two years that required chronic therapy (with the exception of occasional acute or mild exercise induced asthma). * Patients with some nasal conditions, or with clinically significant nasal deformity or any recent nasal surgery or trauma that has not completely healed. * Upper respiratory tract infection or any untreated infections within the previous 30 days. * Patient has started immunotherapy/changed the dose within 30 days of starting the study or has desensitization therapy to the seasonal allergen that is causing the allergic rhinitis within the previous 6 months. * Patients with a history of tuberculosis, or with the presence of glaucoma, cataracts, ocular herpes simplex, conjunctivitis or other eye infection not related to the diagnosis of seasonal allergic rhinitis within 14 days of enrollment. * The patient has had recent exposure (30 days) or was at risk of being exposed to chicken pox or measles. * Any known hypersensitivity to mometasone, other steroids or any of the components of the study nasal spray. * Planned travel outside of the local area for more than 2 consecutive days or 3 days in total. * The patient has a history of alcohol or drug abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population) | Baseline, 14 days | Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS patients 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. 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 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 Nasal Symptom Score (iTNSS) (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 iTNSS patients 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. 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 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. |
| Clinical Global Improvement Based on the Investigator's Assessment | Day 15 | A global evaluation of efficacy relative to baseline was assessed separately by the investigator and the patient on Day 15. Both the investigator and the patient were asked to rate clinical improvement since baseline on a 5-category scale ranging from No Relief to Complete Relief of signs and symptoms of seasonal allergic rhinitis. This record shows the clinical global improvement based on the investigator's assessment. |
| Clinical Global Improvement Based on the Patient's Assessment | Day 15 | A global evaluation of efficacy relative to baseline was assessed separately by the investigator and the patient on Day 15. Both the investigator and the patient were asked to rate clinical improvement since baseline on a 5-category scale ranging from No Relief to Complete Relief of signs and symptoms of seasonal allergic rhinitis. This record shows the clinical global improvement based on the patient's assessment. |
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 Mometasone furoate 50 mcg/actuation nasal spray (Lek Pharmaceuticals) administered once daily at a dose of 200 mcg (4 actuations) for 14 days. | 317 |
| Reference Mometasone furoate (Nasonex®) 50 mcg/actuation nasal spray administered once daily at a dose of 200 mcg (4 actuations) for 14 days. | 320 |
| Placebo Placebo nasal spray administered once daily for 14 days. | 158 |
| Total | 795 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 |
| Overall Study | Enrolled in error | 0 | 1 | 1 |
| Overall Study | Lost to follow up | 1 | 1 | 0 |
| Overall Study | Other | 0 | 2 | 0 |
| Overall Study | Restricted medication for seasonal allergic rhinitis | 0 | 0 | 1 |
| Overall Study | Withdrew consent | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Test | Reference | Placebo | Total |
|---|---|---|---|---|
| Age, Customized < 18 | 28 Participants | 39 Participants | 12 Participants | 79 Participants |
| Age, Customized 18 - 40 | 147 Participants | 139 Participants | 77 Participants | 363 Participants |
| Age, Customized 41 - 64 | 130 Participants | 125 Participants | 63 Participants | 318 Participants |
| Age, Customized 65 - 75 | 9 Participants | 16 Participants | 5 Participants | 30 Participants |
| Age, Customized > 75 | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Black/African American | 39 Participants | 35 Participants | 15 Participants | 89 Participants |
| Race/Ethnicity, Customized Native Hawaiian / Other Pacific Islander | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 5 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 271 Participants | 277 Participants | 140 Participants | 688 Participants |
| Sex: Female, Male Female | 205 Participants | 207 Participants | 109 Participants | 521 Participants |
| Sex: Female, Male Male | 112 Participants | 113 Participants | 49 Participants | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 317 | 0 / 320 | 0 / 158 |
| other Total, other adverse events | 5 / 317 | 5 / 320 | 5 / 158 |
| serious Total, serious adverse events | 0 / 317 | 0 / 320 | 0 / 158 |
Outcome results
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 | Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Equivalence: Per-Protocol Population) | 1.981 score on scale | Standard Deviation 2.335 |
| Reference | Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Equivalence: Per-Protocol Population) | 1.817 score on scale | Standard Deviation 2.258 |
90% CI: [91.86, 123.997]
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 | Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | 2.008 score on scale | Standard Deviation 2.356 |
| Reference | Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | 1.794 score on scale | Standard Deviation 2.257 |
| Placebo | Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | 1.034 score on scale | Standard Deviation 1.894 |
p-value: <0.0001ANCOVA
p-value: 0.0001ANCOVA
Secondary
Clinical Global Improvement Based on the Investigator's Assessment
A global evaluation of efficacy relative to baseline was assessed separately by the investigator and the patient on Day 15. Both the investigator and the patient were asked to rate clinical improvement since baseline on a 5-category scale ranging from No Relief to Complete Relief of signs and symptoms of seasonal allergic rhinitis. This record shows the clinical global improvement based on the investigator's assessment.
Time frame: Day 15
Population: Intent-to-Treat Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test | Clinical Global Improvement Based on the Investigator's Assessment | Marked Relief | 68 Participants |
| Test | Clinical Global Improvement Based on the Investigator's Assessment | Moderate Relief | 125 Participants |
| Test | Clinical Global Improvement Based on the Investigator's Assessment | No Relief | 34 Participants |
| Test | Clinical Global Improvement Based on the Investigator's Assessment | Slight Relief | 83 Participants |
| Test | Clinical Global Improvement Based on the Investigator's Assessment | Complete Relief | 4 Participants |
| Reference | Clinical Global Improvement Based on the Investigator's Assessment | Moderate Relief | 119 Participants |
| Reference | Clinical Global Improvement Based on the Investigator's Assessment | No Relief | 53 Participants |
| Reference | Clinical Global Improvement Based on the Investigator's Assessment | Slight Relief | 72 Participants |
| Reference | Clinical Global Improvement Based on the Investigator's Assessment | Marked Relief | 67 Participants |
| Reference | Clinical Global Improvement Based on the Investigator's Assessment | Complete Relief | 3 Participants |
| Placebo | Clinical Global Improvement Based on the Investigator's Assessment | Complete Relief | 0 Participants |
| Placebo | Clinical Global Improvement Based on the Investigator's Assessment | Marked Relief | 23 Participants |
| Placebo | Clinical Global Improvement Based on the Investigator's Assessment | No Relief | 39 Participants |
| Placebo | Clinical Global Improvement Based on the Investigator's Assessment | Moderate Relief | 56 Participants |
| Placebo | Clinical Global Improvement Based on the Investigator's Assessment | Slight Relief | 38 Participants |
p-value: 0.2655Cochran-Mantel-Haenszel
p-value: 0.0009Cochran-Mantel-Haenszel
p-value: 0.1093Cochran-Mantel-Haenszel
Secondary
Clinical Global Improvement Based on the Patient's Assessment
A global evaluation of efficacy relative to baseline was assessed separately by the investigator and the patient on Day 15. Both the investigator and the patient were asked to rate clinical improvement since baseline on a 5-category scale ranging from No Relief to Complete Relief of signs and symptoms of seasonal allergic rhinitis. This record shows the clinical global improvement based on the patient's assessment.
Time frame: Day 15
Population: Intent-to-Treat Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test | Clinical Global Improvement Based on the Patient's Assessment | Marked Relief | 71 Participants |
| Test | Clinical Global Improvement Based on the Patient's Assessment | Moderate Relief | 115 Participants |
| Test | Clinical Global Improvement Based on the Patient's Assessment | No Relief | 33 Participants |
| Test | Clinical Global Improvement Based on the Patient's Assessment | Slight Relief | 83 Participants |
| Test | Clinical Global Improvement Based on the Patient's Assessment | Complete Relief | 12 Participants |
| Reference | Clinical Global Improvement Based on the Patient's Assessment | Moderate Relief | 111 Participants |
| Reference | Clinical Global Improvement Based on the Patient's Assessment | No Relief | 36 Participants |
| Reference | Clinical Global Improvement Based on the Patient's Assessment | Slight Relief | 83 Participants |
| Reference | Clinical Global Improvement Based on the Patient's Assessment | Marked Relief | 73 Participants |
| Reference | Clinical Global Improvement Based on the Patient's Assessment | Complete Relief | 11 Participants |
| Placebo | Clinical Global Improvement Based on the Patient's Assessment | Complete Relief | 1 Participants |
| Placebo | Clinical Global Improvement Based on the Patient's Assessment | Marked Relief | 24 Participants |
| Placebo | Clinical Global Improvement Based on the Patient's Assessment | No Relief | 27 Participants |
| Placebo | Clinical Global Improvement Based on the Patient's Assessment | Moderate Relief | 58 Participants |
| Placebo | Clinical Global Improvement Based on the Patient's Assessment | Slight Relief | 46 Participants |
p-value: 0.9915Cochran-Mantel-Haenszel
p-value: 0.0312Cochran-Mantel-Haenszel
p-value: 0.0487Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population)
Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS patients 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. 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 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) | 1.900 score on scale | Standard Deviation 2.408 |
| Reference | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population) | 1.656 score on scale | Standard Deviation 2.207 |
90% CI: [93.316, 129.159]
Secondary
Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population)
Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS patients 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. 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 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) | 1.932 score on scale | Standard Deviation 2.419 |
| Reference | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population) | 1.630 score on scale | Standard Deviation 2.214 |
| Placebo | Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population) | 0.905 score on scale | Standard Deviation 1.914 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA