Seasonal Allergic Rhinitis
Conditions
Brief summary
Study to evaluate the two different strengths and dose regimen of GSP 301 to be effective in treatment of seasonal allergic rhinitis.
Interventions
DRUGGSP 301-1 NS (QD)
GSP 301-1 NS (665 μg olopatadine hydrochloride/50 μg mometasone furoate) administered as 2 sprays/nostril
DRUGGSP 301-2 NS (BID)
GSP 301-2 NS (665 μg olopatadine hydrochloride/25 μg mometasone furoate) administered as 2 sprays/nostril
GSP 301 placebo NS administered as 2 sprays/nostril
DRUGOlopatadine HCl-1 NS (QD)
Olopatadine HCl-1 NS (665 μg) administered as 2 sprays/nostril
DRUGOlopatadine HCl-2 NS (BID)
Olopatadine HCl-2 NS (665 μg) administered as 2 sprays/nostril
DRUGMometasone Furoate-1 NS (QD)
Mometasone furoate -1 NS (50 μg) administered as 2 sprays/nostril
DRUGMometasone Furoate-2 NS (BID)
Mometasone furoate-2 NS (25 μg) administered as 2 sprays/nostril
Sponsors
Glenmark Pharmaceuticals Ltd. India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Aged ≥12 years and older inclusive of either sex. 2. Documented clinical history of SAR (for at least 2 years preceding the Screening Visit \[Visit 1\]) with exacerbations (clinical evidence of active symptoms) during the study season for the mountain cedar pollen 3. A 12-hour reflective TNSS ≥ 8 out of a possible 12 and a congestion score of ≥ 2 for the AM assessment at the Screening Visit (Visit 1). Key
Exclusion criteria
1. Pregnant or lactating women. 2. Plans to travel outside the known pollen area for the investigative site for \> 24 hours during the last 7 days of run in period. 3. History of nasal polyps of other clinically significant respiratory tract malformations, recent nasal biopsy, nasal trauma (such as nasal piercing) or surgery, atopic dermatitis or rhinitis medicamentosa. 4. History of anaphylaxis and/or other severe local reaction(s) to skin testing. 5. History of positive test for HIV, Hepatitis B or Hepatitis C infection. 6. Documented evidence of acute or significant chronic sinusitis or chronic purulent postnasal drip. 7. Subjects with an active pulmonary disorder or infection. 8. Subjects with posterior subcapsular cataracts or glaucoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in rTNSS From Baseline to End of Treatment | 14 days | Subjects were asked to assess rTNSS (reflective Total Nasal Symptom Score), ie, an evaluation of symptom severity over the past 12 hours prior to the recording of the score. The TNSS was defined as the sum of the subject-reported symptom severity scores for the following four nasal symptoms, recorded by each subject in the diary: rhinorrhea, sneezing, nasal congestion, nasal itching. The total rTNSS scores for all four symptoms (i.e, the lowest possible score (0) and the highest possible score (12).) Higher score means a worse outcome. The severity scale for each symptom evaluation was defined as follows: * 0 = absent (no sign/symptom evident) * 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) * 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) * 3 = severe (sign/symptom that is hard to tolerate \[i.e., causes interference with activities of daily living and/or sleeping\]) |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at 10 sites in the US.
Participants by arm
| Arm | Count |
|---|---|
| GSP 301 Placebo NS GSP 301 placebo NS administered as 2 sprays/nostril | 159 |
| GSP 301-1 NS (QD) GSP 301-1 NS administered as 2 sprays/nostril | 158 |
| Mometasone Furoate-1 NS (QD) Mometasone furoate-1 NS administered as 2 sprays/nostril | 160 |
| Olopatadine HCl-1 NS (QD) Olopatadine HCl-1 NS administered as 2 sprays/nostril | 158 |
| GSP 301-2 NS (BID) GSP 301-2 NS administered as 2 sprays/nostril | 157 |
| Mometasone Furoate-2 NS (BID) Mometasone furoate-2 NS administered as 2 sprays/nostril | 159 |
| Olopatadine HCl-2 NS (BID) Olopatadine HCl-2 NS administered as 2 sprays/nostril | 160 |
| Total | 1,111 |
Baseline characteristics
| Characteristic | GSP 301 Placebo NS | GSP 301-1 NS (QD) | Mometasone Furoate-1 NS (QD) | Olopatadine HCl-1 NS (QD) | GSP 301-2 NS (BID) | Mometasone Furoate-2 NS (BID) | Olopatadine HCl-2 NS (BID) | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.35 years STANDARD_DEVIATION 14.951 | 43.83 years STANDARD_DEVIATION 13.609 | 44.40 years STANDARD_DEVIATION 14.312 | 41.90 years STANDARD_DEVIATION 12.478 | 43.44 years STANDARD_DEVIATION 14.128 | 44.58 years STANDARD_DEVIATION 13.698 | 43.49 years STANDARD_DEVIATION 13.868 | 43.86 years STANDARD_DEVIATION 13.882 |
| Sex: Female, Male Female | 112 Participants | 100 Participants | 115 Participants | 105 Participants | 111 Participants | 96 Participants | 101 Participants | 740 Participants |
| Sex: Female, Male Male | 47 Participants | 58 Participants | 45 Participants | 53 Participants | 46 Participants | 63 Participants | 59 Participants | 371 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 159 | 0 / 158 | 0 / 160 | 0 / 158 | 0 / 157 | 0 / 159 | 0 / 160 |
| serious Total, serious adverse events | 0 / 159 | 1 / 158 | 0 / 160 | 0 / 158 | 0 / 157 | 0 / 159 | 0 / 160 |
Outcome results
Primary
Change in rTNSS From Baseline to End of Treatment
Subjects were asked to assess rTNSS (reflective Total Nasal Symptom Score), ie, an evaluation of symptom severity over the past 12 hours prior to the recording of the score. The TNSS was defined as the sum of the subject-reported symptom severity scores for the following four nasal symptoms, recorded by each subject in the diary: rhinorrhea, sneezing, nasal congestion, nasal itching. The total rTNSS scores for all four symptoms (i.e, the lowest possible score (0) and the highest possible score (12).) Higher score means a worse outcome. The severity scale for each symptom evaluation was defined as follows: * 0 = absent (no sign/symptom evident) * 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) * 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) * 3 = severe (sign/symptom that is hard to tolerate \[i.e., causes interference with activities of daily living and/or sleeping\])
Time frame: 14 days
Population: The full analysis set (FAS) included all randomized subjects who received at least one dose of randomized study medication and had at least one post-baseline primary efficacy assessment. This was the primary analysis set for efficacy analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSP 301 Placebo | Change in rTNSS From Baseline to End of Treatment | Change from Baseline to Visit 4 | -1.4 units on a scale | Standard Deviation 2 |
| GSP 301 Placebo | Change in rTNSS From Baseline to End of Treatment | Baseline | 10.3 units on a scale | Standard Deviation 1.18 |
| GSP 301-1 NS (QD) | Change in rTNSS From Baseline to End of Treatment | Change from Baseline to Visit 4 | -2.5 units on a scale | Standard Deviation 2.52 |
| GSP 301-1 NS (QD) | Change in rTNSS From Baseline to End of Treatment | Baseline | 10.4 units on a scale | Standard Deviation 1.24 |
| Mometasone Furoate-1 NS (QD) | Change in rTNSS From Baseline to End of Treatment | Change from Baseline to Visit 4 | -2.2 units on a scale | Standard Deviation 2.68 |
| Mometasone Furoate-1 NS (QD) | Change in rTNSS From Baseline to End of Treatment | Baseline | 10.4 units on a scale | Standard Deviation 1.3 |
| Olopatadine HCl-1 NS (QD) | Change in rTNSS From Baseline to End of Treatment | Baseline | 10.3 units on a scale | Standard Deviation 1.26 |
| Olopatadine HCl-1 NS (QD) | Change in rTNSS From Baseline to End of Treatment | Change from Baseline to Visit 4 | -1.7 units on a scale | Standard Deviation 2.09 |
| GSP 301-2 NS (BID) | Change in rTNSS From Baseline to End of Treatment | Baseline | 10.4 units on a scale | Standard Deviation 1.19 |
| GSP 301-2 NS (BID) | Change in rTNSS From Baseline to End of Treatment | Change from Baseline to Visit 4 | -2.6 units on a scale | Standard Deviation 2.56 |
| Mometasone Furoate-2 NS (BID) | Change in rTNSS From Baseline to End of Treatment | Baseline | 10.5 units on a scale | Standard Deviation 1.13 |
| Mometasone Furoate-2 NS (BID) | Change in rTNSS From Baseline to End of Treatment | Change from Baseline to Visit 4 | -1.9 units on a scale | Standard Deviation 1.88 |
| Olopatadine HCl-2 NS (BID) | Change in rTNSS From Baseline to End of Treatment | Change from Baseline to Visit 4 | -2.1 units on a scale | Standard Deviation 2.26 |
| Olopatadine HCl-2 NS (BID) | Change in rTNSS From Baseline to End of Treatment | Baseline | 10.3 units on a scale | Standard Deviation 1.24 |
p-value: <0.000197.5% CI: [-1.669, -0.5485]ANCOVA
p-value: <0.000197.5% CI: [-1.7315, -0.609]ANCOVA
p-value: 0.00295% CI: [-1.2616, -0.282]ANCOVA
p-value: 0.152495% CI: [-0.8445, 0.1319]ANCOVA
p-value: 0.048895% CI: [-0.981, -0.0025]ANCOVA
p-value: 0.004395% CI: [-1.2031, -0.2235]ANCOVA