Evaluation of Brimonidine Tartrate/Ketotifen Fumarate Combination for the Treatment of Allergic Conjunctivitis

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy of Combo (Drug Product Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution) compared to its individual components and vehicle in a population of subjects with allergic conjunctivitis:

Official Title
-----------------
Evaluation of Combination Drug Product Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution Compared to Its Components and Vehicle for the Treatment of Allergic Conjunctivitis in the Conjunctival Allergen Challenge Model

Conditions
-----------------
Allergic Conjunctivitis

Intervention / Treatment
-----------------
* Drug: Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo
* Drug: Ketotifen fumarate ophthalmic solution 0.035%
* Drug: Brimonidine tartrate ophthalmic solution 0.025%
* Drug: Vehicle ophthalmic solution


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must: be at least 10 years of age of either sex and any race; provide written informed consent and sign a HIPAA form. Subjects who are under the age of 18 will need to sign an assent form as well as having a parent or legal guardian sign an informed consent; be willing and able to follow all instructions and attend all study visits; (If female and of childbearing potential) agree to have urine pregnancy testing performed at visits 2, 4a (must be negative) and at exit visit (Visit 5); 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 the first dose of investigational drug (Visit 4a) and for 1 month after the last dose of investigational drug (Visit 5). 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 the first dose of investigational drug (Visit 4a). 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. throughout the study duration, for at least 14 days prior to the first dose of investigational drug (Visit 4a) and for 1 month after the last dose of the study drug (Visit 5) 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 the first dose of investigational drug (Visit 4a). Without a vasectomy, must use condoms with spermicidal foam/gel/film/cream/suppository. have a history of ocular allergies and a positive skin test reaction to a seasonal (grass, ragweed, tree pollen) or perennial (cat dander, dog dander, dust mites, cockroach) allergen as confirmed by an allergic skin test conducted at Visit 1 or within the past 24 months; have a calculated best-corrected visual acuity of 0.7 LogMar or better in each eye as measured using an ETDRS chart at Visit 2; have a positive bilateral CAC reaction (defined as having scores of ≥ 2 for ocular itching and ≥ 2 for conjunctival redness) within 10 minutes of instillation of the last titration of allergen at Visit 2; have a positive bilateral CAC reaction (defined as having scores of ≥ 2 for ocular itching and ≥ 2 for conjunctival redness) in at least 2 out of 3 timepoints at following the challenge at Visit 3; be able and willing to discontinue wearing contact lenses for at least 72 hours prior to Visit 2 and during the study trial period. Exclusion Criteria: Subjects may not: have known contraindications or sensitivities to the use of any of the investigational product(s) or their components; 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 3 months prior to enrollment (Visit 4a) and/or a history of refractive surgery within 6 months prior to enrollment (Visit 4a); have a known history of retinal detachment, diabetic retinopathy, or progressive retinal disease; have the presence of an active ocular infection (bacterial, viral or fungal), positive history of an ocular herpetic infection, or preauricular lymphadenopathy at any visit; manifest signs or symptoms of clinically active allergic conjunctivitis in either eye at the start of Visits 2, 3, or 4a (defined as a score of >0 for itching and/or >1 for conjunctival redness); use any of the following disallowed medications during the period indicated prior to Visit 2 and agree not to use disallowed medications throughout the study: 7 Days systemic or ocular H1 antihistamines, H1 antihistamine/mast-cell stabilizer drug combinations, H1 antihistamine-vasoconstrictor drug combinations, decongestants, immunotherapeutic agents, monoamine oxidase inhibitors, artificial tears, eye whiteners (eg, vasoconstrictors), lid scrubs, mast cell stabilizers, prostaglandins or prostaglandin derivatives, ocular, topical, or systemic nonsteroidal anti-inflammatory drugs (NSAIDs); *Baby aspirin (81 mg) is allowed as long as a stable dose has been maintained for at least 30 days prior to Visit 1 and will continue to be maintained for the duration of the study. 14 Days inhaled, ocular, topical, or systemic corticosteroids or mast cell stabilizers; 45 Days depo-corticosteroids 2 Months immunosuppressive or cancer chemotherapeutic agents Note: Currently marketed over-the counter anti-allergy eyedrops (i.e., anti-histamine/vasoconstrictor combination products like Visine-A® or Naphcon-A®) may be administered to subjects at the end of each visit, after all evaluations are completed; have any significant illness (for example, any autoimmune disease requiring therapy, or severe cardiovascular disease [including arrhythmias]) the Investigator feels could be expected to interfere with the subject's safety or study parameters and/or put the subject at any unnecessary risk (includes but is not limited to poorly controlled hypertension or poorly controlled diabetes, a history of status asthmaticus, organ transplants, a known history of persistent moderate or severe asthma, or a known history of moderate to severe allergic asthmatic reactions to any of the study allergens);

Ages Eligible for Study
-----------------
Minimum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combination ophthalmic solution, n = 75<br> | Drug: Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>* Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>Drug: Ketotifen fumarate ophthalmic solution 0.035%<br>* Ketotifen fumarate ophthalmic solution 0.035%<br>Drug: Brimonidine tartrate ophthalmic solution 0.025%<br>* Brimonidine tartrate ophthalmic solution 0.025%<br>Drug: Vehicle ophthalmic solution<br>* Vehicle ophthalmic solution<br>|
| Experimental: Ketotifen fumarate ophthalmic solution 0.035% (n = 75)<br> | Drug: Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>* Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>Drug: Ketotifen fumarate ophthalmic solution 0.035%<br>* Ketotifen fumarate ophthalmic solution 0.035%<br>Drug: Brimonidine tartrate ophthalmic solution 0.025%<br>* Brimonidine tartrate ophthalmic solution 0.025%<br>Drug: Vehicle ophthalmic solution<br>* Vehicle ophthalmic solution<br>|
| Experimental: Brimonidine tartrate ophthalmic solution 0.025% (n = 75)<br> | Drug: Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>* Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>Drug: Ketotifen fumarate ophthalmic solution 0.035%<br>* Ketotifen fumarate ophthalmic solution 0.035%<br>Drug: Brimonidine tartrate ophthalmic solution 0.025%<br>* Brimonidine tartrate ophthalmic solution 0.025%<br>Drug: Vehicle ophthalmic solution<br>* Vehicle ophthalmic solution<br>|
| Experimental: Vehicle ophthalmic solution (n = 75)<br> | Drug: Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>* Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% combo<br>Drug: Ketotifen fumarate ophthalmic solution 0.035%<br>* Ketotifen fumarate ophthalmic solution 0.035%<br>Drug: Brimonidine tartrate ophthalmic solution 0.025%<br>* Brimonidine tartrate ophthalmic solution 0.025%<br>Drug: Vehicle ophthalmic solution<br>* Vehicle ophthalmic solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Itching measured by Conjunctival Allergen Challenge Ocular Itching Scale | Ocular itching score (average score of the subject's two eyes) evaluated by the subject at 3(±1), 5(±1), and 7(±1) minutes postCAC (0-4 scale, allowing half unit increments) at Visits 4b and 5 | 15 minutes & 8 hours post-dose from Conjunctival Allergen Challenge (CAC) Model | 
| Conjunctival Redness measured by Ocular Hyperemia Scale | Conjunctival redness score (average score of the subject's two eyes) evaluated by the investigator at 7(±1), 15(±1), and 20(±1) minutes post-CAC (0-4 scale, allowing half unit increments) at Visits 4b and 5 | 15 minutes & 8 hours post-dose from Conjunctival Allergen Challenge (CAC) Model |