Seasonal Allergic Rhinitis
Conditions
Brief summary
This study will evaluate the ability of oral montelukast/loratadine to improve the signs and symptoms of seasonal allergic rhinitis compared with loratadine alone, montelukast alone and placebo.
Interventions
montelukast 10 mg/loratadine 10 mg tablet taken once daily at bed time for 2 weeks
montelukast 10 mg tablet taken once daily at bed time for 2 weeks
loratadine 10 mg tablet taken once daily at bed time for 2 weeks
DRUGComparator: placebo
placebo tablet taken once daily at bed time for 2 weeks
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patient has a documented history of seasonal allergic rhinitis symptoms that flare up during the study season * Patient is a nonsmoker * Patient is in good general health
Exclusion criteria
* Patient is hospitalized * Patient is a woman who is less than 8 weeks postpartum or is breast-feeding * Patient intends to move or vacation away during the study * Patient has had any major surgery within 4 weeks of study start * Patient is a current or past abuser of alcohol or illicit drugs * Patient has been treated in an emergency room for asthma in the past month * Patient had an upper respiratory infection with in 3 weeks prior to study start * Patient has any active pulmonary disorder other than asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Daytime Nasal Symptoms Score | Baseline and Week 2 | Mean change from baseline in Daytime Nasal Symptoms score. Patients were asked to rate each of the 4 nasal symptoms of Congestion, Rhinorrhea, Itching, and Sneezing daily on a 4-point scale (0 (best) to 3 (worst)). The average of the 4 individual nasal symptoms scores was reported as the Daytime Nasal Symptoms Score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Composite Symptoms Score (Daytime Nasal and Nighttime Symptoms) | Baseline and Week 2 | Composite Symptoms scores were computed as the average of the Daytime Nasal Symptoms scores and Nighttime Symptoms scores collected on a 4 point scale (0 (best) to 3 (worst)). |
| Mean Change From Baseline in Daytime Eye Symptoms Score | Baseline and Week 2 | Mean change from baseline in Daytime Eye Symptoms scores. Patients were asked to rate each of the 4 eye symptom of tearing, itchy, red, and puffy eyes daily on a 4-point scale (0 (best) to 3 (worst)). The average of the 4 individual eye symptoms scores was reported as the Daytime Eye Symptoms Score. |
| Mean Change From Baseline in Daytime Nasal Congestion Score | Baseline and Week 2 | Patients were asked to rate the nasal symptom of Congestion daily on a 4-point scale (0 (best) to 3 (worst)). |
| Mean Change From Baseline in Daytime Rhinorrhea Score | Baseline and Week 2 | Patients were asked to rate the nasal symptom of Rhinorrhea daily on a 4-point scale (0 (best) to 3 (worst)). |
| Mean Change From Baseline in Daytime Nasal Itching Score | Baseline and Week 2 | Patients were asked to rate the nasal symptom of Nasal Itching daily on a 4-point scale (0 (best) to 3 (worst)). |
| Mean Change From Baseline in Nighttime Symptoms Score | Baseline and Week 2 | Mean change from baseline in Nighttime Symptoms Score. Patients were asked to rate each symptom daily on a 4-point scale (0 (best) to 3 (worst)), and the combined score of Nasal Congestion Upon Awakening, Difficulty Going to Sleep, and Nighttime Awakenings was reported as the Nighttime Symptoms Score. |
| Mean Change From Baseline in Nasal Congestion Upon Awakening | Baseline and Week 2 | Patients were asked to rate the symptom of Nasal Congestion Upon Awakening daily on a 4-point scale (0 (best) to 3 (worst)). |
| Patient's Global Evaluation of Allergic Rhinitis | Week 2 | An evaluation by the patient, administered at the last visit (or upon discontinuation) using a 7-point scale, of the change in symptoms as compared to the beginning of the study. Responses were assigned numerical values from 0 (very much better) to 6 (very much worse). |
| Physician's Global Evaluation of Allergic Rhinitis | Week 2 | An evaluation by the physician, administered at the last visit (or upon discontinuation) using a 7-point scale, of the change in symptoms as compared to the beginning of the study. Responses were assigned numerical values from 0 (very much better) to 6 (very much worse). |
| Mean Change From Baseline in Rhinoconjunctivitis Quality-of-Life Score | Week 2 | Patients completed a Rhinoconjunctivitis Quality-of-Life Questionnaire, 28 questions on a 7-point scale \[0(best) to 6(worst)\] across 7 domains: activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, emotional. Scores per domain were averaged, then scores for the 7 domains were averaged for an overall score. |
| Mean Change From Baseline in Daytime Sneezing Score | Baseline and Week 2 | Patients were asked to rate the nasal symptom of Sneezing daily on a 4-point scale (0 (best) to 3 (worst)). |
Participant flow
Recruitment details
Forty study centers in the United States. Therapy Period: September 1999 to November 1999
Pre-assignment details
Patients who required excluded medication and those who did not meet a minimum predefined level of combined Daytime Nasal Symptoms score during the run-in period were excluded from randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching-image placebo tablet to each of montelukast, loratadine, and montelukast/loratadine combination orally once daily at bedtime for 2 weeks | 149 |
| Montelukast Montelukast 10 mg tablet and matching-image placebo tablet to each of loratadine and montelukast/loratadine combination orally once daily at bedtime for 2 weeks | 155 |
| Loratadine Loratadine 10 mg tablet and matching-image placebo tablet to each of montelukast and montelukast/loratadine combination orally once daily at bedtime for 2 weeks | 301 |
| Montelukast/Loratadine Montelukast 10 mg/loratadine 10 mg combination tablet and matching-image placebo tablet to each of montelukast and loratadine orally once daily at bedtime for 2 weeks | 302 |
| Total | 907 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 | 1 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 2 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo | Montelukast | Loratadine | Montelukast/Loratadine | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.9 Years | 35.2 Years | 37.1 Years | 37.6 Years | 36.9 Years |
| Composite Symptoms Score (Daytime Nasal and Nighttime Symptoms) | 1.71 Units on a Scale STANDARD_DEVIATION 0.45 | 1.82 Units on a Scale STANDARD_DEVIATION 0.43 | 1.82 Units on a Scale STANDARD_DEVIATION 0.45 | 1.78 Units on a Scale STANDARD_DEVIATION 0.46 | 1.79 Units on a Scale STANDARD_DEVIATION 0.45 |
| Daytime Congestion score | 2.26 Units on a Scale STANDARD_DEVIATION 0.56 | 2.31 Units on a Scale STANDARD_DEVIATION 0.5 | 2.37 Units on a Scale STANDARD_DEVIATION 0.52 | 2.31 Units on a Scale STANDARD_DEVIATION 0.58 | 2.32 Units on a Scale STANDARD_DEVIATION 0.54 |
| Daytime Eye Symptoms Score | 1.31 Units on a Scale STANDARD_DEVIATION 0.73 | 1.38 Units on a Scale STANDARD_DEVIATION 0.73 | 1.38 Units on a Scale STANDARD_DEVIATION 0.78 | 1.38 Units on a Scale STANDARD_DEVIATION 0.77 | 1.37 Units on a Scale STANDARD_DEVIATION 0.76 |
| Daytime Nasal Itching score | 1.94 Units on a Scale STANDARD_DEVIATION 0.67 | 1.94 Units on a Scale STANDARD_DEVIATION 0.7 | 1.93 Units on a Scale STANDARD_DEVIATION 0.79 | 1.89 Units on a Scale STANDARD_DEVIATION 0.73 | 1.92 Units on a Scale STANDARD_DEVIATION 0.74 |
| Daytime Nasal Symptoms Score | 2.01 Units on a Scale STANDARD_DEVIATION 0.44 | 2.06 Units on a Scale STANDARD_DEVIATION 0.39 | 2.09 Units on a Scale STANDARD_DEVIATION 0.44 | 2.01 Units on a Scale STANDARD_DEVIATION 0.43 | 2.04 Units on a Scale STANDARD_DEVIATION 0.43 |
| Daytime Rhinorrhea score | 2.02 Units on a Scale STANDARD_DEVIATION 0.7 | 2.05 Units on a Scale STANDARD_DEVIATION 0.61 | 2.16 Units on a Scale STANDARD_DEVIATION 0.58 | 1.98 Units on a Scale STANDARD_DEVIATION 0.66 | 2.06 Units on a Scale STANDARD_DEVIATION 0.64 |
| Daytime Sneezing score | 1.81 Units on a Scale STANDARD_DEVIATION 0.74 | 1.93 Units on a Scale STANDARD_DEVIATION 0.65 | 1.89 Units on a Scale STANDARD_DEVIATION 0.74 | 1.87 Units on a Scale STANDARD_DEVIATION 0.68 | 1.87 Units on a Scale STANDARD_DEVIATION 0.71 |
| Nasal Congestion Upon Awakening | 2.17 Units on a Scale STANDARD_DEVIATION 0.65 | 2.25 Units on a Scale STANDARD_DEVIATION 0.56 | 2.26 Units on a Scale STANDARD_DEVIATION 0.61 | 2.20 Units on a Scale STANDARD_DEVIATION 0.63 | 2.23 Units on a Scale STANDARD_DEVIATION 0.62 |
| Nighttime Symptoms Score | 1.32 Units on a Scale STANDARD_DEVIATION 0.65 | 1.50 Units on a Scale STANDARD_DEVIATION 0.64 | 1.47 Units on a Scale STANDARD_DEVIATION 0.63 | 1.46 Units on a Scale STANDARD_DEVIATION 0.66 | 1.45 Units on a Scale STANDARD_DEVIATION 0.65 |
| Rhinoconjunctivitis Quality-of-Life Score | 3.06 Units on a Scale STANDARD_DEVIATION 1.09 | 3.14 Units on a Scale STANDARD_DEVIATION 0.98 | 3.10 Units on a Scale STANDARD_DEVIATION 1.02 | 3.25 Units on a Scale STANDARD_DEVIATION 1.08 | 3.15 Units on a Scale STANDARD_DEVIATION 1.05 |
| Sex: Female, Male Female | 86 Participants | 102 Participants | 191 Participants | 208 Participants | 587 Participants |
| Sex: Female, Male Male | 63 Participants | 53 Participants | 110 Participants | 94 Participants | 320 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 | 8 / 149 | 5 / 155 | 13 / 301 | 10 / 302 |
| serious Total, serious adverse events | 1 / 149 | 0 / 155 | 0 / 301 | 0 / 302 |
Outcome results
Primary
Mean Change From Baseline in Daytime Nasal Symptoms Score
Mean change from baseline in Daytime Nasal Symptoms score. Patients were asked to rate each of the 4 nasal symptoms of Congestion, Rhinorrhea, Itching, and Sneezing daily on a 4-point scale (0 (best) to 3 (worst)). The average of the 4 individual nasal symptoms scores was reported as the Daytime Nasal Symptoms Score.
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Daytime Nasal Symptoms Score | -0.26 Units on a Scale |
| Montelukast | Mean Change From Baseline in Daytime Nasal Symptoms Score | -0.48 Units on a Scale |
| Loratadine | Mean Change From Baseline in Daytime Nasal Symptoms Score | -0.52 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Daytime Nasal Symptoms Score | -0.58 Units on a Scale |
Secondary
Change From Baseline in Composite Symptoms Score (Daytime Nasal and Nighttime Symptoms)
Composite Symptoms scores were computed as the average of the Daytime Nasal Symptoms scores and Nighttime Symptoms scores collected on a 4 point scale (0 (best) to 3 (worst)).
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Composite Symptoms Score (Daytime Nasal and Nighttime Symptoms) | -0.2 Units on a Scale |
| Montelukast | Change From Baseline in Composite Symptoms Score (Daytime Nasal and Nighttime Symptoms) | -0.40 Units on a Scale |
| Loratadine | Change From Baseline in Composite Symptoms Score (Daytime Nasal and Nighttime Symptoms) | -0.41 Units on a Scale |
| Montelukast/Loratadine | Change From Baseline in Composite Symptoms Score (Daytime Nasal and Nighttime Symptoms) | -0.45 Units on a Scale |
Secondary
Mean Change From Baseline in Daytime Eye Symptoms Score
Mean change from baseline in Daytime Eye Symptoms scores. Patients were asked to rate each of the 4 eye symptom of tearing, itchy, red, and puffy eyes daily on a 4-point scale (0 (best) to 3 (worst)). The average of the 4 individual eye symptoms scores was reported as the Daytime Eye Symptoms Score.
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Daytime Eye Symptoms Score | -0.14 Units on a Scale |
| Montelukast | Mean Change From Baseline in Daytime Eye Symptoms Score | -0.35 Units on a Scale |
| Loratadine | Mean Change From Baseline in Daytime Eye Symptoms Score | -0.38 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Daytime Eye Symptoms Score | -0.41 Units on a Scale |
Secondary
Mean Change From Baseline in Daytime Nasal Congestion Score
Patients were asked to rate the nasal symptom of Congestion daily on a 4-point scale (0 (best) to 3 (worst)).
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Daytime Nasal Congestion Score | -0.19 Units on a Scale |
| Montelukast | Mean Change From Baseline in Daytime Nasal Congestion Score | -0.41 Units on a Scale |
| Loratadine | Mean Change From Baseline in Daytime Nasal Congestion Score | -0.39 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Daytime Nasal Congestion Score | -0.43 Units on a Scale |
Secondary
Mean Change From Baseline in Daytime Nasal Itching Score
Patients were asked to rate the nasal symptom of Nasal Itching daily on a 4-point scale (0 (best) to 3 (worst)).
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Daytime Nasal Itching Score | -0.26 Units on a Scale |
| Montelukast | Mean Change From Baseline in Daytime Nasal Itching Score | -0.49 Units on a Scale |
| Loratadine | Mean Change From Baseline in Daytime Nasal Itching Score | -0.56 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Daytime Nasal Itching Score | -0.62 Units on a Scale |
Secondary
Mean Change From Baseline in Daytime Rhinorrhea Score
Patients were asked to rate the nasal symptom of Rhinorrhea daily on a 4-point scale (0 (best) to 3 (worst)).
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Daytime Rhinorrhea Score | -0.25 Units on a Scale |
| Montelukast | Mean Change From Baseline in Daytime Rhinorrhea Score | -0.53 Units on a Scale |
| Loratadine | Mean Change From Baseline in Daytime Rhinorrhea Score | -0.51 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Daytime Rhinorrhea Score | -0.59 Units on a Scale |
Secondary
Mean Change From Baseline in Daytime Sneezing Score
Patients were asked to rate the nasal symptom of Sneezing daily on a 4-point scale (0 (best) to 3 (worst)).
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Daytime Sneezing Score | -0.26 Units on a Scale |
| Montelukast | Mean Change From Baseline in Daytime Sneezing Score | -0.46 Units on a Scale |
| Loratadine | Mean Change From Baseline in Daytime Sneezing Score | -0.59 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Daytime Sneezing Score | -0.67 Units on a Scale |
Secondary
Mean Change From Baseline in Nasal Congestion Upon Awakening
Patients were asked to rate the symptom of Nasal Congestion Upon Awakening daily on a 4-point scale (0 (best) to 3 (worst)).
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Nasal Congestion Upon Awakening | -0.15 Units on a Scale |
| Montelukast | Mean Change From Baseline in Nasal Congestion Upon Awakening | -0.35 Units on a Scale |
| Loratadine | Mean Change From Baseline in Nasal Congestion Upon Awakening | -0.30 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Nasal Congestion Upon Awakening | -0.32 Units on a Scale |
Secondary
Mean Change From Baseline in Nighttime Symptoms Score
Mean change from baseline in Nighttime Symptoms Score. Patients were asked to rate each symptom daily on a 4-point scale (0 (best) to 3 (worst)), and the combined score of Nasal Congestion Upon Awakening, Difficulty Going to Sleep, and Nighttime Awakenings was reported as the Nighttime Symptoms Score.
Time frame: Baseline and Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Nighttime Symptoms Score | -0.12 Units on a Scale |
| Montelukast | Mean Change From Baseline in Nighttime Symptoms Score | -0.29 Units on a Scale |
| Loratadine | Mean Change From Baseline in Nighttime Symptoms Score | -0.26 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Nighttime Symptoms Score | -0.28 Units on a Scale |
Secondary
Mean Change From Baseline in Rhinoconjunctivitis Quality-of-Life Score
Patients completed a Rhinoconjunctivitis Quality-of-Life Questionnaire, 28 questions on a 7-point scale \[0(best) to 6(worst)\] across 7 domains: activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, emotional. Scores per domain were averaged, then scores for the 7 domains were averaged for an overall score.
Time frame: Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle, i.e., all patients who had a baseline and at least one posttreatment measurement were included. No missing values were imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Rhinoconjunctivitis Quality-of-Life Score | -0.80 Units on a Scale |
| Montelukast | Mean Change From Baseline in Rhinoconjunctivitis Quality-of-Life Score | -1.09 Units on a Scale |
| Loratadine | Mean Change From Baseline in Rhinoconjunctivitis Quality-of-Life Score | -1.06 Units on a Scale |
| Montelukast/Loratadine | Mean Change From Baseline in Rhinoconjunctivitis Quality-of-Life Score | -1.16 Units on a Scale |
Secondary
Patient's Global Evaluation of Allergic Rhinitis
An evaluation by the patient, administered at the last visit (or upon discontinuation) using a 7-point scale, of the change in symptoms as compared to the beginning of the study. Responses were assigned numerical values from 0 (very much better) to 6 (very much worse).
Time frame: Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle. Since only 1 measurement was obtained during the treatment period, no missing values were imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Patient's Global Evaluation of Allergic Rhinitis | 2.37 Units on a Scale |
| Montelukast | Patient's Global Evaluation of Allergic Rhinitis | 2.10 Units on a Scale |
| Loratadine | Patient's Global Evaluation of Allergic Rhinitis | 2.00 Units on a Scale |
| Montelukast/Loratadine | Patient's Global Evaluation of Allergic Rhinitis | 1.92 Units on a Scale |
Secondary
Physician's Global Evaluation of Allergic Rhinitis
An evaluation by the physician, administered at the last visit (or upon discontinuation) using a 7-point scale, of the change in symptoms as compared to the beginning of the study. Responses were assigned numerical values from 0 (very much better) to 6 (very much worse).
Time frame: Week 2
Population: The primary efficacy analyses were based on the intention-to-treat (all-patients-treated) principle. Since only 1 measurement was obtained during the treatment period, no missing values were imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Physician's Global Evaluation of Allergic Rhinitis | 2.35 Units on a Scale |
| Montelukast | Physician's Global Evaluation of Allergic Rhinitis | 2.13 Units on a Scale |
| Loratadine | Physician's Global Evaluation of Allergic Rhinitis | 2.05 Units on a Scale |
| Montelukast/Loratadine | Physician's Global Evaluation of Allergic Rhinitis | 1.99 Units on a Scale |