Efficacy and Safety of Grass Sublingual Tablet in Adults (P05238 AM3)(COMPLETED)

Study Overview
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Brief Summary
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This purpose of this study is to determine the efficacy and safety of a grass sublingual (under-the-tongue) tablet.

Detailed Description
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This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study in participants 18 to 65 years of age, of either sex, and of any race with a history of grass pollen induced rhinoconjunctivitis with or without asthma. While receiving treatment, participants will receive either grass sublingual tablet or placebo. Open-label rescue medications for the hinoconjunctivitis and asthma symptoms will be provided. Participants will visit the study site for at least 12 visits. A total of 10 allergic symptoms, 6 rhinoconjunctivitis and 4 lung symptoms, will be recorded daily on an electronic diary by the participant. The start and end of the grass pollen season (GPS) was determined based on the regional grass pollen count, and lasted up to 162 days. For each region, the GPS is defined as the first day of 3 consecutive recorded days with a grass pollen count of ≥ 10 grains/m^3, to the last day of the last occurrence of 3 consecutive recorded days with a grass pollen count ≥ 10 grains/m^3, inclusively.

Official Title
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A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of Grass (Phleum Pratense) Sublingual Tablet (SCH 697243) in Adult Subjects With a History of Grass Pollen Induced Rhinoconjunctivitis With or Without Asthma

Conditions
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Rhinoconjunctivitis, Rhinitis, Conjunctivitis, Allergy

Intervention / Treatment
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* Drug: Placebo
* Biological: SCH 697243
* Drug: Loratadine 10 mg Rescue Treatment
* Drug: Olopatadine 0.1% Rescue Treatment
* Drug: Mometasone 50 mcg Rescue Treatment
* Drug: Prednisone 5 mg Rescue Treatment
* Drug: Albuterol sulfate 108 mcg
* Drug: Fluticasone propionate 44 mcg
* Drug: Prednisone 5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be 18 to 65 years of age, of either sex, and of any race. Participants must have a clinical history of significant allergic rhinoconjunctivitis to grass (with or without asthma) diagnosed by a physician and have received treatment for their disease during the previous GPS. Participants must have a positive skin prick test response (average wheal diameter >=5 mm larger than the saline control after 15 to 20 minutes) to Phleum pratense at the Screening Visit. Participants must be positive for specific IgE against Phleum pratense (>=IgE Class 2) at the Screening Visit. Participants must have an FEV1 >=70% of predicted value at the Screening Visit. Participants' safety laboratory tests, vital signs and ECG conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor. Participant must be willing to give written informed consent and be able to adhere to dose and visit schedules. Female participants of childbearing potential must be using a medically acceptable and adequate form of birth control. These include: hormonal contraceptives as prescribed by a physician (oral, hormonal vaginal ring, hormonal implant or depot injectable); medically prescribed intra-uterine device; medically prescribed topically-applied transdermal contraceptive patch; double-barrier method (eg, condom in combination with a spermicide); vasectomy and tubal ligation should each be considered as single barrier. Female participants of childbearing potential should be counseled in the appropriate use of birth control while in the study. Female participants who are not currently sexually active must agree and consent to use one of the above-mentioned methods if they become sexually active while participating in the study. Female participants of childbearing potential must have a negative urine pregnancy test at the Screening Visit in order to be considered eligible for enrollment. Exclusion Criteria: Participants with a clinical history of symptomatic seasonal allergic rhinitis and/or asthma, having received regular medications due to another allergen during or potentially overlapping the GPS. Participants with a clinical history of significant symptomatic perennial allergic rhinitis and/or asthma having received regular medication due to an allergen to which the subject is regularly exposed. Participants with sufficient pre-seasonal data in the observational phase will not be eligible to continue in the treatment phase if the subject: 1) does not experience an increase in rhinoconjunctivitis symptom score of equal to or greater than 4 above the pre-seasonal average symptom score for at least 2 days, 2) does not use allergy rescue medication for at least 2 days, during the observational phase Year 1 2008 GPS. Participants that received an immunosuppressive treatment within 3 months prior to the Screening Visit (except steroids for allergic and asthma symptoms). Participants with a clinical history of severe asthma. Participants with history of anaphylaxis with cardiorespiratory symptoms. Participants with a history of self-injectable epinephrine use. Participants with a history of chronic urticaria and angioedema. Participants with clinical history of chronic sinusitis during the 2 years prior to the Screening Visit. Participants with current severe atopic dermatitis. Female participants who are breast-feeding, pregnant, or intending to become pregnant. Participatns who have had previous treatment by immunotherapy with grass pollen allergen or any other allergen within the 5 years prior to the Screening Visit. Participants with a known history of allergy, hypersensitivity or intolerance to the ingredients of the investigational medicinal products (except for Phleum pratense), rescue medications, or self-injectable epinephrine. Participants with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study. Specific examples include but are not limited to hypertension being treated with beta blockers, coronary artery disease, arrhythmia, stroke, ocular conditions requiring topical beta blockers, any condition requiring the use of beta blockers. Participants that have used any investigational drugs within 30 days of the Screening Visit. Participants that are participating in any other clinical study. Participants that are a family member of the investigational study staff conducting this study. Participants that are unable to meet medication washout requirements as listed in the protocol. Participants that are unlikely to be able to complete the trial, for any reason, or likely to travel for extended periods of time during the GPS, which in the opinion of the investigator will compromise the data. Participants with a clinically significant abnormal vital sign or laboratory value that would preclude participation in the study. Participants participating in this study may not participate in this same study at another investigational site. Participants must not be randomized into this study more than once. Participants who are unable to or will not comply with the use of self-injectable epinephrine. Participants that may be at greater risk of developing adverse reactions after epinephrine administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching Placebo | Drug: Placebo<br>* Placebo sublingual tablet<br>Drug: Loratadine 10 mg Rescue Treatment<br>* Loratadine 10 mg RediTabs tablets were dosed orally once daily as rescue medication among participants with a total symptom score ≥ 4 during the GPS.<br>* Other names: Claritin;Drug: Olopatadine 0.1% Rescue Treatment<br>* Olopatadine hydrochloride 0.1% ophthalmic solution was administered intraocularly at a dose of 1 drop in each affected eye twice daily as rescue medication for rhinoconjunctivitis, as needed.<br>* Other names: Pantanol;Drug: Mometasone 50 mcg Rescue Treatment<br>* Mometasone furoate monohydrate nasal spray 50 mcg was admininstered intranasally at a dose of 2 sprays in each nostril once daily as rescue medication for rhinoconjunctivitis, as needed.<br>* Other names: Nasonex;Drug: Prednisone 5 mg Rescue Treatment<br>* Prednisone 5 mg tablets were administered orally at a dose of 1 mg/kg/day (maximum 50 mg/day) on Day 1 and 0.5 mg/kg/day (maximum 25 mg/day) on Days 2, 3, 5 and 7 as rescue medication for rhinoconjunctivitis among participants with a total symptom score of ≥ 4 despite treatment with loratadine and mometasone furoate nasal spray.<br>* Other names: Sterapred DS;Drug: Albuterol sulfate 108 mcg<br>* Albuterol sulfate inhalation aerosol 108 mcg/inhalation was administed via inhalation at a dose of 2 inhalations every 4 to 6 hours, as needed, as rescue medication for asthma.<br>* Other names: Vospire;Drug: Fluticasone propionate 44 mcg<br>* Fluticasone propionate inhalation aerosol 44 mcg/inhalation was administered via inhalation at a dose of two inhalations twice daily, to a maximum dose of 10 inhalations twice daily, as rescue medication for asthma among participants utilizing four or more albuterol sulfate inhalations/day for 2 days for nocturnal asthma or shortness of breath.<br>* Other names: Flonase;Drug: Prednisone 5 mg<br>* Prednisone 5 mg tablets were administered orally at a dose of 1 mg/kg/day (maximum 50 mg/day) on Day 1 and 0.5 mg/kg/day (maximum 25 mg/day) on Days 2, 3, 5 and 7 as rescue medication for asthma at the discretion of the investigator for the treatment of asthma exacerbation.<br>* Other names: Sterapred DS;|
| Experimental: SCH 697243<br> | Biological: SCH 697243<br>* SCH 697243 (2800 Bioequivalent Allergen Units [BAU] of Phleum pratense extract, containing approximately 15 mcg Phl p 5), administered sublingually once daily.<br>* Other names: Phleum pratense extract;Drug: Loratadine 10 mg Rescue Treatment<br>* Loratadine 10 mg RediTabs tablets were dosed orally once daily as rescue medication among participants with a total symptom score ≥ 4 during the GPS.<br>* Other names: Claritin;Drug: Olopatadine 0.1% Rescue Treatment<br>* Olopatadine hydrochloride 0.1% ophthalmic solution was administered intraocularly at a dose of 1 drop in each affected eye twice daily as rescue medication for rhinoconjunctivitis, as needed.<br>* Other names: Pantanol;Drug: Mometasone 50 mcg Rescue Treatment<br>* Mometasone furoate monohydrate nasal spray 50 mcg was admininstered intranasally at a dose of 2 sprays in each nostril once daily as rescue medication for rhinoconjunctivitis, as needed.<br>* Other names: Nasonex;Drug: Prednisone 5 mg Rescue Treatment<br>* Prednisone 5 mg tablets were administered orally at a dose of 1 mg/kg/day (maximum 50 mg/day) on Day 1 and 0.5 mg/kg/day (maximum 25 mg/day) on Days 2, 3, 5 and 7 as rescue medication for rhinoconjunctivitis among participants with a total symptom score of ≥ 4 despite treatment with loratadine and mometasone furoate nasal spray.<br>* Other names: Sterapred DS;Drug: Albuterol sulfate 108 mcg<br>* Albuterol sulfate inhalation aerosol 108 mcg/inhalation was administed via inhalation at a dose of 2 inhalations every 4 to 6 hours, as needed, as rescue medication for asthma.<br>* Other names: Vospire;Drug: Fluticasone propionate 44 mcg<br>* Fluticasone propionate inhalation aerosol 44 mcg/inhalation was administered via inhalation at a dose of two inhalations twice daily, to a maximum dose of 10 inhalations twice daily, as rescue medication for asthma among participants utilizing four or more albuterol sulfate inhalations/day for 2 days for nocturnal asthma or shortness of breath.<br>* Other names: Flonase;Drug: Prednisone 5 mg<br>* Prednisone 5 mg tablets were administered orally at a dose of 1 mg/kg/day (maximum 50 mg/day) on Day 1 and 0.5 mg/kg/day (maximum 25 mg/day) on Days 2, 3, 5 and 7 as rescue medication for asthma at the discretion of the investigator for the treatment of asthma exacerbation.<br>* Other names: Sterapred DS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Total Combined Symptom (TCS) Score Over the Entire Grass Pollen Season (GPS) | The TCS is the sum of the rhinoconjunctivitis daily symptom score (DSS) and rhinoconjunctivitis daily medication score (DMS) averaged over the entire GPS. The TCS ranged from 0-54, with increasing score indicating a higher level of symptom severity. The DSS is composed of 6 rhinoconjunctivitis symptoms with scores from 0-18, with increasing score indicating increased severity. The DMS is composed of a sum of the scores associated with rescue medication use per day. The range for the DMS was 0-36, with a lower score indicating less use of rescue medication. | Start of the GPS to End of the GPS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Average Rhinoconjunctivitis Daily Symptom Score (DSS) Over the Entire GPS | The DSS is composed of six rhinoconjunctivitis symptoms which were recorded daily including runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy, and watery eyes, and the symptoms were measured on a scale of 0 (no symptom) to 3 (severe symptoms). A higher score indicated a higher level of symptoms and the total daily score could range from 0 to 18. | Start of the GPS to End of the GPS | 
| Participant Average Rhinoconjunctivitis Daily Medication Score (DMS) Over the Entire GPS | The DMS is composed of a sum of the scores associated with rescue medication use per day. Rescue medications were implemented when a participant had a symptom score >= 4. Rescue medications for allergic rhinoconjunctivitis were to be utilized in a step-wise fashion: loratadine, olopatadine hydrochloride 0.1% opthalmic solution, mometasone, and prednisone, in that sequence. The score for the DMS ranged from 0-36. A lower medication score indicated less impact on symptomology and was suggestive of less use of rescue medication. | Start of the GPS to End of the GPS | 
| Participant Average Weekly Rhinoconjunctivitis Quality-of-Life Questionnaire With Standardized Activities (RQLQ(S)) Total Score Over the Entire GPS | The RQLQ(s) has 28 questions and focusses on 7 domains that may be significantly impaired in participants with seasonal allergic rhinoconjunctivitis: sleep impairment, non-nasal symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, and emotional difficulty. The RQLQ score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. RQLQ scores range from 0-6, with a higher score indicating more significant impairment. | Start of the GPS to End of the GPS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhinoconjunctivitis, rhinitis, conjunctivitis, allergy, allergen, immunotherapy