Efficacy and Safety Study of Desloratadine (MK-4117) in Japanese Participants With Seasonal Allergic Rhinitis (MK-4117-204)

Study Overview
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Brief Summary
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This is an efficacy and safety study of desloratadine (MK-4117) in Japanese participants with seasonal allergic rhinitis (SAR). The primary hypothesis of this study is that the change from Baseline in Total Nasal Symptom Score (TNSS) is improved by desloratadine compared to placebo.

Detailed Description
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This study consists of a one-week Symptom Confirmation Period during which participants undergo a single-blinded placebo run-in, a two-week double-blind Treatment Period and a two-week Follow-up Period.

Official Title
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A Phase III, Multi-Center, Randomized, Placebo-Controlled, Double-Blind Trial to Study the Efficacy and Safety of MK-4117 in Japanese Subjects With Seasonal Allergic Rhinitis

Conditions
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Seasonal Allergic Rhinitis

Intervention / Treatment
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* Drug: Desloratadine 5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has at least a 2-year history of seasonal allergic rhinitis with typical symptoms Male or female who is unlikely to conceive: a surgically sterilized female, female who has reached natural menopause, or is of reproductive potential and agrees to either remain abstinent or use (or have her partner use) 2 acceptable methods of birth control from study start through 14 days after the last dose of study drug. Exclusion Criteria: Has a lower respiratory tract infection or has a nasopharyngolaryngeal infection (acute upper respiratory tract infection, acute pharyngolaryngitis, or acute tonsillitis, etc.) requiring treatment Has a coexisting infection or systemic mycosis for which there are no effective antibiotics Has asthma that is under treatment and/or uncontrolled Has nasal septum ulcers, nasal surgery, or nasal trauma which have not healed Has vasomotor rhinitis or eosinophilic rhinitis Has a history of hypersensitivity to antihistamines or ingredients of study drug Has had treatment with corticosteroids (oral, injectable, suppository, depot drugs [injectable]) or immunological drugs within 28 days prior to Visit 2 Is currently receiving treatment with another investigational drug or has received an investigational drug within prior 3 months Has started specific desensitization therapy (allergen immunotherapy) or nonspecific allassotherapy (Histaglobin, vaccine therapy, etc.) or who has received such therapies within prior 3 months Has received coagulation or resection using laser therapy etc. for treatment for nasal symptoms Will receive nasal nebulizer therapy and/or thermotherapy during study period Has severe hepatic, renal, cardiac, hematological disease, or other serious coexisting diseases and whose general condition is poor Has a history of malignancy or clinically important hematological disorder, except for adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix Has a history of severe drug allergy (e.g. anaphylactoid reaction) Is pregnant or lactating or may be pregnant Is planning a remote trip for more than 1 day during the Symptom Confirmation Period or for more than 2 days during the Treatment Period.

Ages Eligible for Study
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Minimum Age: 16 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Desloratadine<br>After a 1-week single-blinded placebo run-in during which SAR symptoms are confirmed (Confirmation of Symptom Period), participants receive double-blinded desloratadine (one 5 mg tablet) orally (PO) once daily (QD) in the morning for 2 weeks during the Treatment Period. | Drug: Desloratadine 5 mg<br>* Desloratadine 5 mg tablets<br>|
| Placebo Comparator: Placebo<br>After a 1-week single-blinded placebo run-in during which SAR symptoms are confirmed (Confirmation of Symptom Period), participants receive double-blinded placebo (one tablet) PO QD in the morning for 2 weeks during the Treatment Period. | Drug: Placebo<br>* Placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Nasal Symptom Score (TNSS) During 2 Weeks of Therapy | The TNSS was used to evaluate participant nasal symptoms of: sneezing (daily frequency of attacks scored from 0 [<1 time or none] to 4 [≥21 times]), rhinorrhea (daily frequency of blowing nose scored from 0 [<1 time or none] to 4 [≥21 times]), nasal congestion (scored from 0 [no nasal blockage] to 4 [completely obstructed all day]), and nasal itching (scored from 0 [none] to 4 [nose is itchy, requiring frequent rubbing or blowing nose) as rated in the participant's diary. The TNSS was the sum of the 4 nasal symptom sub-scores. TNSS scores ranged from 0 to 16, with a higher score indicating more frequent/severe nasal symptoms. Baseline (BL) measurement was an average of scores for 3 days prior to treatment (during Confirmation of Symptom Period). Post-BL measurement was an average from Day 1 to Day 13 (2 week average). Change from BL = Post BL measurement - BL measurement. | Baseline, Day 1 to Day 13 (Weeks 1 through 2 average) of double-blind treatment | 
| Number of Participants Who Experience at Least One Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. | Up to 4 weeks (Up to 2 weeks after last dose of study drug) | 
| Number of Participants Who Discontinue Study Drug Due to an AE | An AE was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. | Up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in TNSS for Week 1 and Week 2 of Double-blind Treatment | The TNSS was used to evaluate participant nasal symptoms of: sneezing (daily frequency of attacks scored from 0 [<1 time or none] to 4 [≥21 times]), rhinorrhea (daily frequency of blowing nose scored from 0 [<1 time or none] to 4 [≥21 times]), nasal congestion (scored from 0 [no nasal blockage] to 4 [completely obstructed all day]), and nasal itching (scored from 0 [none] to 4 [nose is itchy, requiring frequent rubbing or blowing nose) as rated in the participant's diary. The TNSS was the sum of the 4 nasal symptom sub-scores. TNSS scores ranged from 0 to 16, with a higher score indicating more frequent/severe nasal symptoms. Baseline (BL) measurement was an average of scores for 3 days prior to treatment (during Confirmation of Symptom Period). Post-BL measurement for Week 1 was an average from Day 1 to Day 7 and post-BL measurement for Week 2 was an average from Day 8 to Day 13. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 1 to 7 (Week 1 average), Day 8 to 13 (Week 2 average) of double-blind treatment | 
| Change From Baseline to Week 1 in Each Nasal Symptom Sub-Score (Sneezing, Rhinorrhea, Nasal Congestion and Nasal Itching) | Nasal symptoms sub-scores rated in the participant's diary included sneezing (daily frequency of attacks scored from 0 [<1 time or none] to 4 [≥21 times]), rhinorrhea (daily frequency of blowing nose scored from 0 [<1 time or none] to 4 [≥21 times]), nasal congestion (scored from 0 [no nasal blockage] to 4 [completely obstructed all day]), and nasal itching (scored from 0 [none] to 4 [nose is itchy, requiring frequent rubbing or blowing nose). Nasal symptom sub-scores ranged from 0 to 4, with a higher score indicating more frequent/severe nasal symptoms. BL measurement was an average of scores for 3 days prior to treatment (during Confirmation of Symptom Period). Post-BL measurement for Week 1 was an average of scores from Day 1 to Day 7. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 1 to 7 (Week 1 average) of double-blind treatment | 
| Change From Baseline to Week 2 in Each Nasal Symptom Sub-Score (Sneezing, Rhinorrhea, Nasal Congestion and Nasal Itching) | Nasal symptoms sub-scores rated in the participant's diary included sneezing (daily frequency of attacks scored from 0 [<1 time or none] to 4 [≥21 times]), rhinorrhea (daily frequency of blowing nose scored from 0 [<1 time or none] to 4 [≥21 times]), nasal congestion (scored from 0 [no nasal blockage] to 4 [completely obstructed all day]), and nasal itching (scored from 0 [none] to 4 [nose is itchy, requiring frequent rubbing or blowing nose). Nasal symptom sub-scores ranged from 0 to 4, with a higher score indicating more frequent/severe nasal symptoms. BL measurement was an average of scores for 3 days prior to treatment (during Confirmation of Symptom Period). Post-BL measurement for Week 2 was an average of scores from Day 8 to Day 13. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 8 to 13 (Week 2 average) of double-blind treatment | 
| Change From Baseline in Each Nasal Symptom Sub-Score (Sneezing, Rhinorrhea, Nasal Congestion and Nasal Itching) During 2 Weeks of Therapy | Nasal symptoms sub-scores rated in the participant's diary included sneezing (daily frequency of attacks scored from 0 [<1 time or none] to 4 [≥21 times]), rhinorrhea (daily frequency of blowing nose scored from 0 [<1 time or none] to 4 [≥21 times]), nasal congestion (scored from 0 [no nasal blockage] to 4 [completely obstructed all day]), and nasal itching (scored from 0 [none] to 4 [nose is itchy, requiring frequent rubbing or blowing nose). Nasal symptom sub-scores ranged from 0 to 4, with a higher score indicating more frequent/severe nasal symptoms. BL measurement was an average of scores for 3 days prior to treatment (during Confirmation of Symptom Period). Post-BL measurement for 2 week Average was an average of scores from Day 1 to Day 13. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 1 to Day 13 (Weeks 1 through 2 average) | 
| Change From Baseline to Week 1 in Eye Symptoms (Pruritus, Watering Eyes and the Worse One of Either Pruritus or Watering Eyes) | Eye symptoms rated in the participant's diary included eye pruritis (eye itching scored from 0 [none] to 4 [severe eye itching, requiring frequent rubbing of eye]) and watering eyes (scored from 0 [none] to 4 [severe eye watering requiring frequent wiping of eyes]). Eye symptom scores ranged from 0 to 4, with a higher score indicating greater severity of symptom. The change from baseline in eye pruritis, eye watering, and the worse one of either eye symptom were reported. Baseline measurement was an average of scores for 3 days prior to treatment. Post-baseline measurement for Week 1 was an average of scores from Day 1 to Day 7. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 1 to 7 (Week 1 average) of double-blind treatment | 
| Change From Baseline to Week 2 in Eye Symptoms (Pruritus, Watering Eyes and the Worse One of Either Pruritus or Watering Eyes) | Eye symptoms rated in the participant's diary included eye pruritis (eye itching scored from 0 [none] to 4 [severe eye itching, requiring frequent rubbing of eye]) and watering eyes (scored from 0 [none] to 4 [severe eye watering requiring frequent wiping of eyes]). Eye symptom scores ranged from 0 to 4, with a higher score indicating greater severity of symptom. The change from baseline in eye pruritis, eye watering, and the worse one of either eye symptom were reported. Baseline measurement was an average of scores for 3 days prior to treatment. Post-BL measurement for Week 2 was an average of scores from Day 8 to Day 13. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 8 to 13 (Week 2) of double-blind treatment | 
| Change From Baseline in Eye Symptoms (Pruritus, Watering Eyes and the Worse One of Either Pruritus or Watering Eyes) During 2 Weeks of Therapy | Eye symptoms rated in the participant's diary included eye pruritis (eye itching scored from 0 [none] to 4 [severe eye itching, requiring frequent rubbing of eye]) and watering eyes (scored from 0 [none] to 4 [severe eye watering requiring frequent wiping of eyes]). Eye symptom scores ranged from 0 to 4, with a higher score indicating greater severity of symptom. The change from baseline in eye pruritis, eye watering, and the worse one of either eye symptom were reported. BL measurement was an average of scores for 3 days prior to treatment. Post-BL measurement for 2 week Average was an average of scores from Day 1 to Day 13. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 1 to Day 13 (Weeks 1 through 2 average) | 
| Change From Baseline in Interference With Daily Activities Score at Week 1, Week 2, and During 2 Weeks of Therapy | Interference of allergic rhinitis symptoms with overall daily activities (such as work, study, housekeeping, sleep, or outing) was rated by the participant according to the following scale: 0=none, 1= symptoms cause few troubles, 2=symptoms cause intermediate problems between 1 and 3, 3=nasal symptoms cause painful and complicating daily life, or 4 = symptoms make daily activities impossible. Interference with daily activities scores ranged from 0 to 4 maximum, with a higher score indicating greater interference with daily activities. Baseline measurement was an average of scores for 3 days prior to treatment. Post-baseline measurement for Week 1 was an average of scores from Day 1 to Day 7. Post-BL measurement for Week 2 was an average of scores from Day 8 to Day 13. Post-BL measurement for 2 week Average was an average of scores from Day 1 to Day 13. Change from BL = Post BL measurement - BL measurement. | Baseline, Day 1 to 7 (Week 1 average), Day 8 to 13 (Week 2 average), Day 1 to Day 13 (Weeks 1 through 2 average) of double-blind treatment | 
| Percentage of Participants With Impression Assessments of Better or Much Better as Assessed by the Investigator at Week 2 | The investigator assessed the participant's symptoms of allergic rhinitis and nasal findings at the end of the study (2 week visit or discontinuation visit) compared with those at the start of the study period (based on their recollection/memory of the participant's symptoms, no formal baseline assessment) and evaluated their impression of study drug on effect according to 6 grades: Much better, Better, Slightly better, Unchanged, Worse, or Unevaluable. The evaluation result and reason for judgment (if needed) was recorded in the participant's case report form. The investigator's impression was evaluated based on the symptoms for allergic rhinitis, nasal findings and participant's own impression at Week 2. The percentage of participants with assessments of Better and Much better graded by the investigator (Investigator's Impression Rate) was reported and analyzed using Odds Ratio analysis. | From Baseline to Week 2 | 
| Percentage of Participants With Impression Assessments of Better or Much Better as Assessed Participants at Week 2 | The participant evaluated their symptoms of allergic rhinitis at the end of the study (2 week visit or discontinuation visit) compared with those at the start of the study period (based on their recollection/memory of their symptoms, no formal baseline assessment) and recorded in their Subject Allergy Diary their impression of study drug on effect according to 6 grades: Much better, Better, Slightly better, Unchanged, Worse, or Unevaluable. The percentage of participants with assessments of Better and Much better graded by the participant (Participant's Impression Rate) was reported and analyzed using Odds Ratio analysis. | From Baseline to Week 2 |