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, parallel-group study in subjects with moderate-to-severe SAR. The study will be conducted at 8 investigational sites during the 2007-2008 Texas Mountain Cedar allergy season. After a 7-day 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), consisting of the sum of the scores of sneezing, nasal congestion, runny nose, and nasal itching. On Days -7 through 14, subjects will rate the TNSS symptoms, the 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. The 12-hour reflective TNSS, the instantaneous TNSS, the 12-hour reflective score for postnasal drip, the 12-hour reflective TOSS, and the instantaneous TOSS will be calculated based on these scores. Additional secondary efficacy variables will include reflective and individual nasal and ocular symptom scores and change from Baseline to Day 14 in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Subjects ≥ 18 years of age will complete the adult 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
DRUGMP29-02
azelastine HCl 548 mcg / fluticasone propionate 200 mcg nasal spray one spray per nostril twice a day
DRUGazelastine Hcl
azelastine Hcl nasal spray one spray per nostril two times a day
DRUGfluticasone propionate
fluticasone propionate 200 mcg nasal spray one spray per nostril two times a day
DRUGplacebo
placebo nasal spray one spray per nostril two times a day
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 subjects 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 willing and able to provide informed consent and to participate in all study procedures * Positive skin test to a prevalent Texas Mountain Cedar allergen
Exclusion criteria
* On Focused Nasal Examination, the presence of any nasal mucosal erosion, nasal ulceration, or nasal septal perforation (Grade 1b - 4) at either the screening visit or randomization visit will disqualify the subject from the study. * Other nasal disease(s) likely to affect deposition of intranasal medication, such as sinusitis, rhinitis medicamentosa, clinically significant polyposis, or nasal structural abnormalities. * Nasal surgery or sinus surgery within the previous year. * Chronic sinusitis - more than 3 episodes per year * Planned travel outside of the study area during the study period * The use of any investigational drug within 30 days prior to Day screening. No investigational products are permitted for use during the conduct of this study * Presence of any hypersensitivity to drugs similar to azelastine hydrochloride or fluticasone propionate * Women who are pregnant or nursing * Women of childbearing potential who are not abstinent or not practicing a medically acceptable method of contraception\* see section 6.1.1 * Respiratory Tract Infections within 14 days prior to Day screening * Respiratory Tract Infections requiring antibiotic treatment 14 days prior to screening * Asthma (with the exception of mild, intermittent asthma). Subjects with mild, intermittent asthma who only require short-acting inhaled bronchodilators (not more often than twice per week) and who do not have nocturnal awakening as a result of asthma are eligible for enrollment * Significant pulmonary disease including COPD * Clinically significant arrhythmia or symptomatic cardiac conditions * A known history of alcohol or drug abuse within the last 2 years * Existence of any surgical or medical condition or physical or laboratory findings, which in the opinion of the investigator or sponsor's medical monitor, might significantly alter the absorption, distribution, metabolism, or excretion of study drug; that might significantly affect the subject's ability to complete this trial; or their safety in this trial. * Clinically relevant abnormal physical findings within 1 week of randomization which, in the opinion of the investigator, would interfere with the objectives of the study or that may preclude compliance with the study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | day 1 to day14 | change from baseline in the 12 hour reflective total nasal symptoms 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. |
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 the 12 hour instantaneous total nasal symptoms 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. |
| Change From Baseline in Adult ( Greater Than 18 Years of Age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | day 1 to day 14 | Change from Baseline in adult ( greater than 18 years of age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the end of 14 days The measurement scale is 0 to 24. A reduction in symptom severity score is indicated by a negative value. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azelastine HCl 548 Mcg / Fluticasone Propionate 200 Mcg azelastine Hcl/ fluticasone propionate nasal spray one spray per nostril two times a day | 153 |
| Azelastine Hcl 548 Mcg azelastine Hcl nasal spray one spray per nostril two times a day | 152 |
| Fluticasone Propionate 200 Mcg fluticasone propionate nasal spray one spray per nostril two times a day | 151 |
| Placebo nasal spray | 151 |
| Total | 607 |
Baseline characteristics
| Characteristic | Azelastine Hcl 548 Mcg | Fluticasone Propionate 200 Mcg | Azelastine HCl 548 Mcg / Fluticasone Propionate 200 Mcg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 10 Participants | 9 Participants | 13 Participants | 43 Participants |
| Age, Categorical >=65 years | 9 Participants | 4 Participants | 8 Participants | 7 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 132 Participants | 137 Participants | 136 Participants | 131 Participants | 536 Participants |
| Age Continuous | 39.5 years STANDARD_DEVIATION 14.1 | 38.1 years STANDARD_DEVIATION 14.2 | 39.5 years STANDARD_DEVIATION 14.2 | 39.9 years STANDARD_DEVIATION 14.7 | 39.2 years STANDARD_DEVIATION 14.3 |
| Region of Enrollment United States | 152 participants | 151 participants | 153 participants | 151 participants | 607 participants |
| Sex: Female, Male Female | 97 Participants | 100 Participants | 97 Participants | 102 Participants | 396 Participants |
| Sex: Female, Male Male | 55 Participants | 51 Participants | 56 Participants | 49 Participants | 211 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 | 28 / 153 | 15 / 152 | 13 / 151 | 10 / 151 |
| serious Total, serious adverse events | 0 / 153 | 0 / 152 | 0 / 151 | 0 / 151 |
Outcome results
Primary
Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS)
change from baseline in the 12 hour reflective total nasal symptoms 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.
Time frame: day 1 to day14
Population: Intent to Treat (ITT) population includes all subjects who were randomized and had at least one post baseline efficacy observation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azelastine HCl 548 Mcg / Fluticasone Propionate 200 Mcg | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -5.3 units on a scale | Standard Deviation 5.1 |
| Azelastine Hcl 548 Mcg | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -3.3 units on a scale | Standard Deviation 4.2 |
| Fluticasone Propionate 200 Mcg | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -3.8 units on a scale | Standard Deviation 4.8 |
| Placebo | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -2.2 units on a scale | Standard Deviation 4.2 |
Secondary
Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS)
change from baseline in the 12 hour instantaneous total nasal symptoms 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.
Time frame: day 1 to day 14
Population: Intent to Treat (ITT) population includes all subjects who were randomized and had at least one post baseline efficacy evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azelastine HCl 548 Mcg / Fluticasone Propionate 200 Mcg | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -4.4 units on a scale | Standard Deviation 5.2 |
| Azelastine Hcl 548 Mcg | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -3.0 units on a scale | Standard Deviation 4.5 |
| Fluticasone Propionate 200 Mcg | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -3.5 units on a scale | Standard Deviation 4.8 |
| Placebo | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -1.7 units on a scale | Standard Deviation 4.2 |
Secondary
Change From Baseline in Adult ( Greater Than 18 Years of Age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days
Change from Baseline in adult ( greater than 18 years of age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the end of 14 days The measurement scale is 0 to 24. A reduction in symptom severity score is indicated by a negative value.
Time frame: day 1 to day 14
Population: Intent to Treat(ITT) population (18 years of age or older) who have had at least one post baseline efficacy evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azelastine HCl 548 Mcg / Fluticasone Propionate 200 Mcg | Change From Baseline in Adult ( Greater Than 18 Years of Age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -1.6 units on a scale | Standard Deviation 1.4 |
| Azelastine Hcl 548 Mcg | Change From Baseline in Adult ( Greater Than 18 Years of Age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -1.2 units on a scale | Standard Deviation 1.3 |
| Fluticasone Propionate 200 Mcg | Change From Baseline in Adult ( Greater Than 18 Years of Age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -1.4 units on a scale | Standard Deviation 1.4 |
| Placebo | Change From Baseline in Adult ( Greater Than 18 Years of Age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | -1.0 units on a scale | Standard Deviation 1.3 |