Seasonal Allergic Rhinitis
Conditions
Brief summary
The purpose of this study is to determine if two allergy medications (azelastine and fluticasone) are more effective than placebo or either medication alone (azelastine or fluticasone)
Detailed description
This will be a Phase III, randomized, double-blind, placebo-controlled, parallel-group study in subjects with moderate-to-severe seasonal allergic rhinitis (SAR). The study will begin with a 7-day, single-blind, placebo lead-in period (Day -7 to Day 1). Subjects will be instructed to take placebo lead-in medication twice daily (1 spray per nostril), approximately every 12 hours. On Day 1, subjects who satisfy the symptom severity requirements and continue to meet all of the study inclusion/exclusion criteria will be randomized in a 1:1:1:1 ratio to receive 1 spray per nostril twice daily of MP29-02, azelastine hydrochloride, fluticasone propionate, or placebo nasal spray. Efficacy will be assessed by the change from baseline in the subject-reported 12-hour reflective Total Nasal Symptom Score (TNSS). On Days 1 through 14, subjects will rate the instantaneous and reflective TNSS symptoms of sneezing, nasal congestion, runny nose, and nasal itching; the instantaneous and reflective total ocular symptom score (TOSS) symptoms of itchy eyes, watery eyes and eye redness; and the symptom of postnasal drip, twice daily (AM and PM) in a diary prior to the dose of study medication. Symptoms will be scored on a 0 to 3 scale (0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms), such that the maximum daily symptom severity score will be 24 for the TNSS and 18 for the TOSS. Additional secondary efficacy variables will include reflective individual nasal and ocular symptom scores, as well as change from Baseline to Day 14 in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Subjects ≥ 18 years of age will complete the RQLQ on Day 1 (prior to dosing) and Day 14. Subjects will return to the clinic on Day 7 for an interim evaluation. After completing the 2-week double-blind treatment period, subjects will return to the clinic on Day 14 (or at time of early termination) for an end-of-study evaluation. Safety and tolerability assessments will be made on Days 7 and 14. Tolerability will be evaluated by subject-reported adverse events (AEs), nasal examinations, and vital signs assessments.
Interventions
DRUGPlacebo
placebo
DRUGazelastine Hcl
azelastine Hcl 548 mcg
DRUGazelastineHcl / fluticasone propionate
azelastine Hcl 548 mcg / fluticasone propionate 200 mcg
DRUGfluticasone propionate
fluticasone propionate 200 mcg
Sponsors
Meda Pharmaceuticals
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 and female patients 12 years of age and older with a 2 year history of moderate to severe seasonal allergic rhinitis * Must be in generally good health * Must meet minimum symptom requirements, as specified in the protocol * Must be wiling and able to provide informed consent and to participate all study procedures * Positive skin test to a prevalent spring allergen
Exclusion criteria
* On nasal examination,the presence of nasal mucosal erosion, nasal ulceration or nasal septal perforation * Nasal disease likely to affect the deposition of the medication or evaluation, such as sinus infection, nasal polyps or severe deviated septum * Nasal or sinus surgery within the previous 6 months * Chronic sinus infection (more than 3 per year) * Planned travel outside the study area during the study period * Use of any investigational drug within 30 days of the first visit * Hypersensitivity (bad reaction) to azelastine hydrchloride nasal spray (Astelin), or fluticasone propionate nasal spray (Flonase) * Women who are not using an acceptable method or birth control * Women who are pregnant or nursing * Upper respiratory tract infection such as common cold, flu, sinus infection within 2 weeks of first study visit * Asthma or other lung diseases such as COPD. Mild asthma symptoms may be considered after consultation with the investigator * Irregular heartbeat or other symptomatic heart conditions * History of alcohol or drug abuse * History of glaucoma * Use of medications that could affect the study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 12-hour Reflective Total Nasal Symptom Score (rTNSS) | days 1 to 14 | change from baseline in 12-hour reflective(how did you feel in the last 12 hours) total nasal symptom score (rTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period. The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.The more negative value the better the result. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | day 1 to day 14 | change from baseline in 12-hour instantaneous ( how do you feel now) total nasal symptom score (iTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period. The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.The more negative the value the better the result. |
| Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | day 1 to day 14 | adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scored at day 1(baseline) and at day 14. The scale is measured from a value of 0 to 24. A negative number corresponds to a change from baseline measurement.The more negative the value the better the result. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MP29-02 MP29-02(fluticasone propionate 50 mcg / azelastine HCl 137 mcg) nasal spray | 207 |
| Fluticasone Propionate fluticasone propionate nasal spray | 207 |
| Azelastine HCl azelastine HCl nasal spray nasal spray | 208 |
| Placebo placebo nasal spray | 210 |
| Total | 832 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | administrative | 1 | 4 | 2 | 1 |
| Overall Study | Adverse Event | 4 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 2 |
| Overall Study | Protocol Violation | 2 | 2 | 6 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Fluticasone Propionate | Azelastine HCl | MP29-02 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 28 Participants | 19 Participants | 36 Participants | 98 Participants |
| Age, Categorical >=65 years | 7 Participants | 8 Participants | 5 Participants | 8 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 185 Participants | 172 Participants | 183 Participants | 166 Participants | 706 Participants |
| Age Continuous | 38.6 years STANDARD_DEVIATION 14.1 | 36.2 years STANDARD_DEVIATION 14.6 | 37.3 years STANDARD_DEVIATION 14.1 | 37.3 years STANDARD_DEVIATION 16 | 37.3 years STANDARD_DEVIATION 14.7 |
| Region of Enrollment United States | 207 participants | 208 participants | 207 participants | 210 participants | 832 participants |
| Sex: Female, Male Female | 127 Participants | 130 Participants | 142 Participants | 133 Participants | 532 Participants |
| Sex: Female, Male Male | 80 Participants | 78 Participants | 65 Participants | 77 Participants | 300 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 | 12 / 207 | 16 / 207 | 19 / 208 | 7 / 210 |
| serious Total, serious adverse events | 0 / 207 | 0 / 207 | 0 / 208 | 0 / 210 |
Outcome results
Primary
Change From Baseline in 12-hour Reflective Total Nasal Symptom Score (rTNSS)
change from baseline in 12-hour reflective(how did you feel in the last 12 hours) total nasal symptom score (rTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period. The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.The more negative value the better the result.
Time frame: days 1 to 14
Population: intent to treat population (ITT)- must have had at least one post baseline efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MP29-02 | Change From Baseline in 12-hour Reflective Total Nasal Symptom Score (rTNSS) | -5.6 units on a scale | Standard Deviation 5.2 |
| Fluticasone Propionate | Change From Baseline in 12-hour Reflective Total Nasal Symptom Score (rTNSS) | -4.7 units on a scale | Standard Deviation 4.7 |
| Azelastine HCl | Change From Baseline in 12-hour Reflective Total Nasal Symptom Score (rTNSS) | -4.2 units on a scale | Standard Deviation 4.6 |
| Placebo | Change From Baseline in 12-hour Reflective Total Nasal Symptom Score (rTNSS) | -2.9 units on a scale | Standard Deviation 3.9 |
Secondary
Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS)
change from baseline in 12-hour instantaneous ( how do you feel now) total nasal symptom score (iTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period. The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.The more negative the value the better the result.
Time frame: day 1 to day 14
Population: intent to treat population (ITT)- must have had at least one post baseline efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MP29-02 | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -5.2 units on a scale | Standard Deviation 5.3 |
| Fluticasone Propionate | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -4.5 units on a scale | Standard Deviation 4.7 |
| Azelastine HCl | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -4.0 units on a scale | Standard Deviation 4.7 |
| Placebo | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -2.6 units on a scale | Standard Deviation 4.1 |
Secondary
Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days
adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scored at day 1(baseline) and at day 14. The scale is measured from a value of 0 to 24. A negative number corresponds to a change from baseline measurement.The more negative the value the better the result.
Time frame: day 1 to day 14
Population: intent to treat( ITT)population (18 yrs of age or older) must have had at least one post baseline efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MP29-02 | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -1.6 units on a scale | Standard Deviation 1.4 |
| Fluticasone Propionate | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -1.6 units on a scale | Standard Deviation 1.2 |
| Azelastine HCl | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -1.4 units on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -0.9 units on a scale | Standard Deviation 1.1 |