Compare the Efficacy of Levocetirizine and Montelukast to Placebo in Reducing Seasonal Allergic Rhinitis (SAR) Symptoms in Ragweed Sensitive Subjects

Study Overview
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Brief Summary
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To compare the clinical efficacy of levocetirizine 5 mg and montelukast 10 mg on symptoms of seasonal allergic rhinitis occurring in subjects exposed to ragweed pollen in an environmental exposure unit.

Official Title
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Double-blind, Three Parallel Randomized Groups, Therapeutic Confirmatory Clinical Trial to Compare the Efficacy of Oral Levocetirizine 5 mg and Montelukast 10 mg to Placebo in Reducing Symptoms of Seasonal Allergic Rhinitis (SAR) in Ragweed Sensitive Subjects Exposed to Ragweed Pollen in an Environmental Exposure Unit (EEU)

Conditions
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Rhinitis, Allergic, Seasonal

Intervention / Treatment
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* Drug: Placebo
* Drug: Montelukast
* Drug: Levocetirizine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had seasonal allergic rhinitis due to Ragweed for the last 2 consecutive years Subjects who obtain a minimum sum score, considering Seasonal Allergic Rhinitis (SAR) related symptoms (mean value), as defined by the protocol Exclusion Criteria: Any clinically significant condition that might interfere with the treatment evaluation, both for efficacy and safety Have used forbidden concomitant medications as defined by the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (PBO)<br>Placebo was administered orally on Days 1 and 2. | Drug: Placebo<br>* Pharmaceutical form: Over-encapsulated tablet Route of administration: Oral use<br>|
| Experimental: Montelukast (MLKT)<br>10 mg of Montelukast (MLKT) was administered orally on Days 1 and 2. | Drug: Montelukast<br>* Pharmaceutical form: Over-encapsulated tablet Concentration: 10 mg Route of administration: Oral use<br>|
| Experimental: Levocetirizine (LCTZ)<br>5 mg of Levocetirizine (LCTZ) was administered orally on Days 1 and 2. | Drug: Levocetirizine<br>* Pharmaceutical form: Over-encapsulated tablet Concentration: 5 mg Route of administration: Oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Major Symptom Complex (MSC) Score Over Period I | Six individual symptoms which are most dominant in the rhinitis symptom profile will be combined to form the MSC severity score: Runny nose (right and left), itchy nose (right and left), sniffles, nose blows, sneezes, watery eyes. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The total MSC score ranges from 0 - 36. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the MSC Score Over Period II | Six individual symptoms which are most dominant in the rhinitis symptom profile will be combined to form the MSC severity score: Runny nose (right and left), itchy nose (right and left), sniffles, nose blows, sneezes, watery eyes. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The total MSC score ranges from 0 - 36. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period II [Day 2, from 9:30 am to 11:00 am] | 
| Change From Baseline in the MSC Score Over Period III | Six individual symptoms which are most dominant in the rhinitis symptom profile will be combined to form the MSC severity score: Runny nose (right and left), itchy nose (right and left), sniffles, nose blows, sneezes, watery eyes. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The total MSC score ranges from 0 - 36. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period III [Day 2, from drug intake (at 11:00 am) to 3:30 pm] | 
| Change From Baseline in the MSC Score Over the Total Treatment Period (Period I + Period II + Period III) | Six individual symptoms which are most dominant in the rhinitis symptom profile will be combined to form the MSC severity score: Runny nose (right and left), itchy nose (right and left), sniffles, nose blows, sneezes, watery eyes. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The total MSC score ranges from 0 - 36. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline to Day 2 | 
| Change From Baseline in the Total Symptom Complex (TSC) Score Over Period I | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The TSC score ranges from 0 to 56. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 
| Change From Baseline in the Total Symptom Complex (TSC) Score Over Period II | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The TSC score ranges from 0 to 56. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period II [Day 2, from 9:30 am to 11:00 am] | 
| Change From Baseline in the Total Symptom Complex (TSC) Score Over Period III | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The TSC score ranges from 0 to 56. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period III [Day 2, from drug intake (at 11:00 am) to 3:30 pm] | 
| Change From Baseline in the Total Symptom Complex (TSC) Score Over the Total Treatment Period (Period I + Period II + Period III) | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The TSC score ranges from 0 to 56. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline to Day 2 | 
| Change From Baseline in the TSC Score + Nasal Congestion Score Over Period I | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. The TSC score plus Nasal congestion score was added and ranged from 0 to 60. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 
| Change From Baseline in the TSC Score + Nasal Congestion Score Over Period II | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. The TSC score plus Nasal congestion score was added and ranged from 0 to 60. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period II [Day 2, from 9:30 am to 11:00 am] | 
| Change From Baseline in the TSC Score + Nasal Congestion Score Over Period III | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. The TSC score plus Nasal congestion score was added and ranged from 0 to 60. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period III [Day 2, from drug intake (at 11:00 am) to 3:30 pm] | 
| Change From Baseline in the TSC Score + Nasal Congestion Score Over the Total Treatment Period (Period I + Period II + Period III) | The TSC score was calculated as the sum of the following 10 individual symptom scores: runny nose (left and right), itchy nose (left and right), sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears, itchy throat, cough and postnasal drip. Each individual symptom, except nose blows and sneezes, is rated on a 5-point scale of severity: 0 = None, 1 = a little, 2 = Moderate, 3 = Quite a bit, 4 = severe, 5 = very severe. For nose blows and sneezes, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. The TSC score plus Nasal congestion score was added and ranged from 0 to 60. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline to Day 2 | 
| Change From Baseline in the Individual Symptom Scores Over Period I | Individual symptom scores include Runny Nose Score, Itchy Nose Score, Sniffles Score, Postnasal Drip Score, Watery Eyes Score, Itchy Eyes and Ears Score, Itchy Throat Score, Cough Score, Sneezes Score, Nose Blows Score, Nasal Congestion Score. The subjects had to evaluate the severity of the symptoms using a scale from None to Very severe (ranging from 0 to 5). For Sneezes Score and Nose Blows Score, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 
| Change From Baseline in the Individual Symptom Scores Over Period II | Individual symptom scores include Runny Nose Score, Itchy Nose Score, Sniffles Score, Postnasal Drip Score, Watery Eyes Score, Itchy Eyes and Ears Score, Itchy Throat Score, Cough Score, Sneezes Score, Nose Blows Score, Nasal Congestion Score. The subjects had to evaluate the severity of the symptoms using a scale from None to Very severe (ranging from 0 to 5). For Sneezes Score and Nose Blows Score, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period II [Day 2, from 9:30 am to 11:00 am] | 
| Change From Baseline in the Individual Symptom Scores Over Period III | Individual symptom scores include Runny Nose Score, Itchy Nose Score, Sniffles Score, Postnasal Drip Score, Watery Eyes Score, Itchy Eyes and Ears Score, Itchy Throat Score, Cough Score, Sneezes Score, Nose Blows Score, Nasal Congestion Score. The subjects had to evaluate the severity of the symptoms using a scale from None to Very severe (ranging from 0 to 5). For Sneezes Score and Nose Blows Score, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline, Treatment Period III [Day 2, from drug intake (at 11:00 am) to 3:30 pm] | 
| Change From Baseline in the Individual Symptom Scores Over the Total Treatment Period (Period I + Period II + Period III) | Individual symptom scores include Runny Nose Score, Itchy Nose Score, Sniffles Score, Postnasal Drip Score, Watery Eyes Score, Itchy Eyes and Ears Score, Itchy Throat Score, Cough Score, Sneezes Score, Nose Blows Score, Nasal Congestion Score. The subjects had to evaluate the severity of the symptoms using a scale from None to Very severe (ranging from 0 to 5). For Sneezes Score and Nose Blows Score, the subjects had to record the number of each symptom since last evaluation. This number corresponds to a score ranging from 0 to 8. The Nasal congestion score ranged from 0 to 4 (0 = clear, 1 = slight block, 2 = stuffy, 3 = very stuffy, 4 = blocked). It corresponds to the mean value of right nostril and left nostril. Increasing scores are associated with increasing severity. Negative values indicate improvement from Baseline. | Baseline to Day 2 | 
| Time to First Feeling of Improvement During Period I | During Period I, the subjects had to record the moment (hh:mm) of first feeling of improvement (compared to Baseline intensity of symptoms). | During Treatment Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 
| Onset of Action During Period I | The onset of action was defined as the first time point during Period I after initiation of the treatment when the reduction from Baseline in the MSC score for the active treatment group became statistically different from the placebo group and when this significant change was maintained for some period of time. | During Treatment Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 
| Intensity of Action From Baseline in the MSC Score Over Period I | The intensity of action was measured by the percentage of subjects with categorized percentage change from Baseline in the MSC score over Period I. Categories are defined as following: < 20%, >=20%, < 50%, >=50%, < 70%, >=70% change from Baseline. | Treatment Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 
| Intensity of Action From Baseline in the MSC Score Over Period II | The intensity of action was measured by the percentage of subjects with categorized percentage change from Baseline in the MSC score over Period II. Categories are defined as following: < 20%, >=20%, < 50%, >=50%, < 70%, >=70% change from Baseline. | Treatment Period II [Day 2, from 9:30 am to 11:00 am] | 
| Intensity of Action From Baseline in the MSC Score Over Period III | The intensity of action was measured by the percentage of subjects with categorized percentage change from Baseline in the MSC score over Period III. Categories are defined as following: < 20%, >=20%, < 50%, >=50%, < 70%, >=70% change from Baseline. | Treatment Period III [Day 2, from drug intake (at 11:00 am) to 3:30 pm] | 
| Variability of Action From Baseline in the MSC Score Over Period I | The variability of action was assessed by the percentage of distribution of the percentage change from Baseline in the MSC score. Categories are defined as following: < 20%, 20%-35%, 35%-50%, 50%-65%, 65%-80%, >=80%. | Period 1 [Day 1, from drug intake (at 11:00 am) to 5 hours post-treatment (at 4:00 pm)] | 
| Variability of Action From Baseline in the MSC Score Over Period II | The variability of action was assessed by the percentage of distribution of the percentage change from Baseline in the MSC score. Categories are defined as following: < 20%, 20%-35%, 35%-50%, 50%-65%, 65%-80%, >=80%. | Treatment Period II [Day 2, from 9:30 am to 11:00 am] | 
| Variability of Action From Baseline in the MSC Score Over Period III | The variability of action was assessed by the percentage of distribution of the percentage change from Baseline in the MSC score. Categories are defined as following: < 20%, 20%-35%, 35%-50%, 50%-65%, 65%-80%, >=80%. | Treatment Period III [Day 2, from drug intake (at 11:00 am) to 3:30 pm] | 
| Global Satisfaction of the Subjects at the End of Period III | Global satisfaction was evaluated at the end of Period III by the subject on a Visual Analog Scale (VAS) ranging from 0 (very dissatisfied) to 100 mm (very satisfied). | At the end of Period III (Day 2) | 
| Percentage of Subjects, at the End of Period III Who Are Willing to Take the Same Medication During the Next Pollen Season | At the end of Period III, each subject without reference to the Symptom Diary Card (SDC) answered to the question: Do you want to take the same treatment during the next pollen season? (yes or no). | At the end of Period III (Day 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levocetirizine, Xyzal, Rhinitis, Allergic, Seasonal, Ragweed