Seasonal Allergic Rhinitis
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of the combination of mometasone furoate nasal spray (MFNS) and oxymetazoline nasal spray (OXY) given together once a day in treating subjects with seasonal allergic rhinitis (SAR) in relieving symptoms including nasal congestion. The secondary objectives of this study are to evaluate the potential of the combination to produce tachyphylaxis and/or rebound congestion, and to evaluate the safety of the combination.
Interventions
DRUGOXY combination: mometasone furoate nasal spray (MFNS) and oxymetazoline nasal spray (OXY)
MFNS 2 sprays per nostril with OXY 1 spray per nostril once daily x 2 weeks. Matching placebo to MFNS given every evening (PM).
DRUGmometasone furoate nasal spray (MFNS) once daily
MFNS 2 sprays per nostril once daily x 2 weeks. Matching placebo to MFNS given every morning (AM) and every evening.
DRUGoxymetazoline nasal spray (OXY) twice daily
OXY 2 sprays per nostril twice daily x 2 weeks. Matching placebo to MFNS given every morning.
DRUGPlacebo
Matching placebo to MFNS given every morning and every evening x 2 weeks.
Sponsors
Quintiles, Inc.
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be 12 years of age or older, of either sex, and of any race. * Must have at least a 2-year documented history of SAR which exacerbates during the time period over which the subject will be participating. * Must have a documented (within the past 12 months) positive skin-prick test response to an appropriate seasonal allergen appropriate to the geographical vicinity in which the study is being carried out and over the period of time the subject is participating. * Must be clinically symptomatic at the Screening and Baseline Visits. * Must be in general good health as confirmed by routine clinical and laboratory testing and electrocardiogram results. * Must be free of any clinically significant disease, other than SAR, which would interfere with the study evaluations. * Must be willing to give written informed consent and must be able to adhere to dosing and visit schedules and study requirements. * Female subjects of child-bearing potential must have a negative serum pregnancy test at screening. Nonsterile and premenopausal female subjects must be using a medically acceptable method of birth control prior to screening and during the entire study. * Must have the ability to transmit electronic diary data on a regular basis.
Exclusion criteria
* A subject with a history of anaphylaxis and/or other severe local reaction(s) to skin testing. * A subject with asthma who requires chronic use of inhaled or systemic corticosteroids. * A subject with current or history of frequent, clinically significant sinusitis or chronic purulent postnasal drip. * A subject with rhinitis medicamentosa. * A subject with glaucoma and/or increased intraocular pressure. * A subject who has nasal structural abnormalities, including large nasal polyps and marked septal deviations, which significantly interfere with nasal air flow. * A subject who, in the opinion of the investigator, is dependent on nasal, oral, or ocular decongestants, nasal topical antihistamines, or nasal steroids. * A pregnant or nursing female. * A subject with current evidence of clinically significant hematopoietic, cardiovascular, hepatic, renal, neurologic, psychiatric, pulmonary, autoimmune disease, or other disease that precludes the subject's participation in the study. Particular attention should be given to exclude subjects with conditions that would currently interfere with the absorption, distribution, metabolism, or excretion of the study drug or interfere with the subject's ability to complete or reliably complete the diaries.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15 | 15 days of treatment | Subjects scored severity of rhinorrhea, nasal congestion/stuffiness, nasal itching, and sneezing at the time of evaluation (NOW) using an ordinal scale from 0 = none to 3 = severe. Evaluations were performed daily in the morning (AM) and evening (PM). For each evaluation, individual symptom scores were summed to a TNSS, which was then averaged for a single score across the 15 day treatment period. |
| Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score | from baseline to hour 4 on Day 1 | Subjects scored nasal congestion/stuffiness using an ordinal scale from 0 = none to 3 = severe. Baseline was the average of the scores assessed every 15 minutes for 1 hour prior to dosing on Day 1. After dosing on Day 1, congestion was scored every 15 minutes for the 1st hour and every 30 minutes for the next 3 hours. Area under the curve (AUC) was calculated using the trapezoid rule, then standardization achieved by dividing the calculation by 4 hours. Treatment comparisons were examined using the standardized AUC(0-4 hr) of the change from baseline to hour 4 on Day 1. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination1 Mometasone Furoate nasal spray (MFNS) with oxymetazoline nasal spray (OXY) 1 spray once daily | 145 |
| Combination3 MFNS with OXY 3 sprays once daily | 139 |
| Mometasone MFNS once daily | 139 |
| Oxymetazoline OXY twice daily | 140 |
| Placebo Placebo nasal spray | 142 |
| Total | 705 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Delay of Study due to Relabeling | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Failed to Comply With Study Requirements | 1 | 1 | 1 | 0 | 1 |
| Overall Study | Increased Blood Pressure at Visit 2 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 1 | 4 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Nonserious Adverse Event (AE) | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Serious or Life-Threatening AE | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Use of Prohibited Medication | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 | 3 | 2 |
| Overall Study | Withdrawn per Sponsor | 0 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Combination1 | Combination3 | Mometasone | Oxymetazoline | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 12 Participants | 5 Participants | 5 Participants | 12 Participants | 42 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 135 Participants | 124 Participants | 132 Participants | 131 Participants | 127 Participants | 649 Participants |
| Sex: Female, Male Female | 93 Participants | 93 Participants | 101 Participants | 95 Participants | 89 Participants | 471 Participants |
| Sex: Female, Male Male | 52 Participants | 46 Participants | 38 Participants | 45 Participants | 53 Participants | 234 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 145 | 5 / 139 | 10 / 139 | 7 / 140 | 8 / 142 |
| serious Total, serious adverse events | 0 / 145 | 0 / 139 | 1 / 139 | 0 / 140 | 1 / 142 |
Outcome results
Primary
Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15
Subjects scored severity of rhinorrhea, nasal congestion/stuffiness, nasal itching, and sneezing at the time of evaluation (NOW) using an ordinal scale from 0 = none to 3 = severe. Evaluations were performed daily in the morning (AM) and evening (PM). For each evaluation, individual symptom scores were summed to a TNSS, which was then averaged for a single score across the 15 day treatment period.
Time frame: 15 days of treatment
Population: Intention to treat (ITT): all randomized subjects who had taken at least one dose of study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Combination1 | Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15 | -3.29 units on a scale | Standard Error 0.209 |
| Combination3 | Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15 | -3.36 units on a scale | Standard Error 0.216 |
| Mometasone | Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15 | -2.97 units on a scale | Standard Error 0.213 |
| Oxymetazoline | Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15 | -2.44 units on a scale | Standard Error 0.215 |
| Placebo | Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15 | -1.90 units on a scale | Standard Error 0.209 |
Comparison: Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same mean change from baseline in AM/PM NOW TNSS as that of OXY twice daily.~Power calculation: The target randomization of 875 subjects (175 subjects per treatment arm) was needed to detect a treatment difference of 0.8 point or more in change from baseline in AM/PM NOW TNSS, with a two-sided alpha of 0.05 and 90% power, assuming a pooled standard deviation of 2.3 points.p-value: 0.002ANCOVA
Comparison: Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same mean change from baseline in AM/PM NOW TNSS as that of OXY twice daily.p-value: <0.001ANCOVA
Comparison: Null hypothesis: the administration of MFNS once daily has the same mean change from baseline in AM/PM NOW TNSS as that of placebo.p-value: <0.001ANCOVA
Primary
Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score
Subjects scored nasal congestion/stuffiness using an ordinal scale from 0 = none to 3 = severe. Baseline was the average of the scores assessed every 15 minutes for 1 hour prior to dosing on Day 1. After dosing on Day 1, congestion was scored every 15 minutes for the 1st hour and every 30 minutes for the next 3 hours. Area under the curve (AUC) was calculated using the trapezoid rule, then standardization achieved by dividing the calculation by 4 hours. Treatment comparisons were examined using the standardized AUC(0-4 hr) of the change from baseline to hour 4 on Day 1.
Time frame: from baseline to hour 4 on Day 1
Population: Intention to treat: all randomized subjects who had taken at least one dose of study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Combination1 | Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score | -0.80 units on a scale | Standard Error 0.056 |
| Combination3 | Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score | -0.92 units on a scale | Standard Error 0.057 |
| Mometasone | Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score | -0.63 units on a scale | Standard Error 0.057 |
| Oxymetazoline | Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score | -1.06 units on a scale | Standard Error 0.057 |
| Placebo | Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score | -0.57 units on a scale | Standard Error 0.056 |
Comparison: Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same standardized AUC(0-4 hr) of the change from baseline in nasal congestion score as that of MFNS once daily.p-value: 0.021ANCOVA
Comparison: Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same standardized AUC (0-4hr) of the change from baseline in nasal congestion score as that of MFNS once dailyp-value: <0.001ANCOVA
Comparison: Null hypothesis: the administration of OXY twice daily has the same standardized AUC(0-4 hr) of the change from baseline in nasal congestion score as that of placebop-value: <0.001ANCOVA