Evaluation of Brimonidine Tartrate/Ketotifen Fumarate Combination in Adults With Seasonal Allergic Conjunctivitis

Study Overview
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Brief Summary
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To evaluate the efficacy of Combo compared to its individual components and compared to vehicle in a population of subjects with seasonal allergic conjunctivitis.

Official Title
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Evaluation of the Combination Drug Product Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution Compared to Its Components and Vehicle in an Allergen BioCube® in Subjects With Seasonal Allergic Conjunctivitis

Conditions
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Seasonal Allergic Conjunctivitis

Intervention / Treatment
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* Drug: Brimonidine Tartrate 0.025%/ Ketotifen Fumarate 0.035% Ophthalmic Solution
* Drug: Ketotifen fumarate ophthalmic solution 0.035% (n = 56)
* Drug: Brimonidine tartrate ophthalmic solution 0.025% (n = 56)
* Drug: Experimental: Vehicle ophthalmic solution (n = 56)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must: be at least 18 years of age of either sex and any race; provide written informed consent and sign the Health Information Portability and Accountability Act (HIPAA) form; be willing and able to follow all instructions and attend all study visits; provide proof of COVID-19 vaccination be able and willing to discontinue wearing contact lenses for at least 72 hours prior to Visit 2 and for the duration of the visit; have seasonal allergic conjunctivitis to ragweed or timothy grass documented by a self-reported history of ocular allergic symptoms for the last 2 consecutive years during the ragweed or timothy grass seasons and a positive skin test reaction to ragweed or timothy grass pollen as confirmed by the allergic skin test given at or within 24 months of the subject's Visit 1; (If female and of childbearing potential) agree to have urine pregnancy testing performed at visit 2, (must be negative); must not be lactating; and must agree to use at least 1 medically acceptable form of birth control throughout the study duration, for at least 14 days prior to and 1 month after receiving investigational drug. Acceptable forms of birth control are true abstinence (when this is in line with the preferred and usual lifestyle of the subject), spermicide with barrier, oral contraceptive, injectable or implantable method of contraception, transdermal contraceptive, intrauterine device, or surgical sterilization of male partner at least 3 months prior to receiving investigational drug (Visit 2). Note: Women considered capable of becoming pregnant include all females who have experienced menarche and have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months) or have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy); (If male and with female partner of childbearing potential) must use at least 1 medically acceptable form of birth control· Note: Acceptable forms of birth control are true abstinence (when this is in line with the preferred and usual lifestyle of the subject) or vasectomy at least 3 months prior to receiving investigational drug (Visit 2). Without a vasectomy, must use condoms with spermicidal foam/gel/film/cream/suppository throughout the study duration, for at least 14 days prior to and 1 month after investigational drug (Visit 2). have a calculated visual acuity (VA) of 0.7 logMAR or better in each eye as measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart at Visit 1; have a positive Allergen BioCube challenge response to pollen exposure at the 90 minute time point of ABC exposure at Visit 2, defined as bilateral score of >2 in ocular itching and ocular redness. Exclusion Criteria: Subjects may not: have known contraindications or sensitivities to the use of any of the investigational product medication or components; have a history of mild persistent, moderate or severe asthma within the preceding 5 years according to the National Heart, Blood, and Lung Institute classification (with the exception of exercise induced asthma). Note: Subjects with fall induced asthma that is either mild persistent (defined as >1 per week, but <1 per day), moderate persistent, or severe persistent will be excluded. have an upper respiratory tract or sinus infection within the previous 2 weeks of Visit 1; have a history of anaphylaxis or poor tolerability of previously administered allergen; have a compromised lung function at Visit 1 (defined as a peak expiratory flow rate [PEFR] that is below 80% of the predicted average PEFR, as calculated by gender, age, and measured height from the Mini-Wright instruction's table: Normal Adult Predicted Average Peak Expiratory Flow). have an abnormal blood pressure (defined as ≤ 90 or ≥ 160 (systolic) measured in mmHg or ≤ 60 or ≥ 100 (diastolic) measured in mmHg) at Visit 1; have any ocular condition that, in the opinion of the investigator, could affect the subject's safety or trial parameters (including but not limited to narrow angle glaucoma, clinically significant blepharitis, follicular conjunctivitis, iritis, pterygium, or a diagnosis of dry eye); have had ocular surgical intervention within three months prior to Visit 1, or during the trial or a history of refractive surgery six months prior to Visit 1, or have systemic surgery planned during the clinical trial or within 30 days after;

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brimonidine Tartrate 0.025%/ Ketotifen Fumarate 0.035% Ophthalmic Solution (n = 56)<br> | Drug: Brimonidine Tartrate 0.025%/ Ketotifen Fumarate 0.035% Ophthalmic Solution<br>* Brimonidine Tartrate 0.025%/ Ketotifen Fumarate 0.035% Ophthalmic Solution<br>|
| Experimental: Ketotifen fumarate ophthalmic solution 0.035% (n = 56)<br> | Drug: Ketotifen fumarate ophthalmic solution 0.035% (n = 56)<br>* Ketotifen fumarate ophthalmic solution 0.035% (n = 56)<br>|
| Experimental: Brimonidine tartrate ophthalmic solution 0.025% (n = 56)<br> | Drug: Brimonidine tartrate ophthalmic solution 0.025% (n = 56)<br>* Brimonidine tartrate ophthalmic solution 0.025% (n = 56)<br>|
| Experimental: Vehicle ophthalmic solution (n = 56)<br> | Drug: Experimental: Vehicle ophthalmic solution (n = 56)<br>* Experimental: Vehicle ophthalmic solution (n = 56)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular itching score subject | Ocular itching score evaluated by the subject at 10(±1), 30(±1), 60(±5), 360(±5), 420(±5), and 480(±5) minutes post-instillation of assigned IP at Visit 2 (0-4 scale, allowing half unit increments), with 4 is the worse outcome. | up to 480 minutes post-instillation of assigned IP | 
| Ocular redness measured by Ocular Itching Scale Investigator using slit lamp | Ocular redness evaluated by the Investigator using slit lamp at 10(±1), 30(±1), 60(±5), 360(±5), 420(±5), and 480(±5) minutes post-instillation of assigned IP at Visit 2 (0-4 scale, allowing half unit increments), with 4 being the worse outcome. | up to 480 minutes post-instillation of assigned IP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tearing measured by watery Eyes Scale | Tearing evaluated by the subject at 10(±1), 30(±1), 60(±5), 360(±5), 420(±5), and 480(±5) minutes post-instillation of assigned IP at Visit 2 (0- 4 scale, NOT allowing half unit increments), with 4 being the worse outcome. | up to 480 minutes post-instillation of assigned IP | 
| Lid swelling measured by Eyelid Swelling Scale | Lid swelling evaluated by the subject at 10(±1), 30(±1), 60(±5), 360(±5), 420(±5), and 480(±5) minutes post-instillation of assigned IP at Visit 2 (0- 3 scale, NOT allowing half unit increments), with 3 being the worst outcome | up to 480 minutes post-instillation of assigned IP | 
| Chemosis evaluated | Chemosis evaluated by the Investigator using slit lamp at 10(±1), 30(±1), 60(±5), 360(±5), 420(±5), and 480(±5) minutes post-instillation of assigned IP at Visit 2 (0-4 scale, allowing half unit increments), with 4 being the worse outcome. | up to 480 minutes post-instillation of assigned IP |