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

Inclusion Criteria:

• Subjects must:

1. be at least 10 years of age of either sex and any race;

2. provide written informed consent and sign a HIPAA form. Subjects who are underthe age of 18 will need to sign an assent form as well as having a parent orlegal guardian sign an informed consent;

3. be willing and able to follow all instructions and attend all study visits;

4. (If female and of childbearing potential) agree to have urine pregnancy testingperformed at visits 2, 4a (must be negative) and at exit visit (Visit 5); mustnot be lactating; and must agree to use at least 1 medically acceptable form ofbirth control throughout the study duration, for at least 14 days prior to thefirst dose of investigational drug (Visit 4a) and for 1 month after the lastdose of investigational drug (Visit 5). Acceptable forms of birth control aretrue abstinence (when this is in line with the preferred and usual lifestyle ofthe subject), spermicide with barrier, oral contraceptive, injectable orimplantable method of contraception, transdermal contraceptive, intrauterinedevice, or surgical sterilization of male partner at least 3 months prior tothe first dose of investigational drug (Visit 4a). Note: Women consideredcapable of becoming pregnant include all females who have experienced menarcheand 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);

5. (If male and with female partner of childbearing potential) must use at least 1medically acceptable form of birth control. throughout the study duration, forat least 14 days prior to the first dose of investigational drug (Visit 4a) andfor 1 month after the last dose of the study drug (Visit 5) Note: Acceptableforms of birth control are true abstinence (when this is in line with thepreferred and usual lifestyle of the subject) or vasectomy at least 3 monthsprior to the first dose of investigational drug (Visit 4a). Without avasectomy, must use condoms with spermicidal foam/gel/film/cream/suppository.

6. have a history of ocular allergies and a positive skin test reaction to aseasonal (grass, ragweed, tree pollen) or perennial (cat dander, dog dander,dust mites, cockroach) allergen as confirmed by an allergic skin test conductedat Visit 1 or within the past 24 months;

7. have a calculated best-corrected visual acuity of 0.7 LogMar or better in eacheye as measured using an ETDRS chart at Visit 2;

8. have a positive bilateral CAC reaction (defined as having scores of ≥ 2 forocular itching and ≥ 2 for conjunctival redness) within 10 minutes ofinstillation of the last titration of allergen at Visit 2;

9. have a positive bilateral CAC reaction (defined as having scores of ≥ 2 forocular itching and ≥ 2 for conjunctival redness) in at least 2 out of 3timepoints at following the challenge at Visit 3;

10. be able and willing to discontinue wearing contact lenses for at least 72 hoursprior to Visit 2 and during the study trial period.

Exclusion Criteria:

• Subjects may not:

1. have known contraindications or sensitivities to the use of any of theinvestigational product(s) or their components;

2. have any ocular condition that, in the opinion of the investigator, couldaffect the subject's safety or trial parameters (including but not limited tonarrow angle glaucoma, clinically significant blepharitis, follicularconjunctivitis, iritis, pterygium, or a diagnosis of dry eye);

3. have had ocular surgical intervention within 3 months prior to enrollment (Visit 4a) and/or a history of refractive surgery within 6 months prior toenrollment (Visit 4a);

4. have a known history of retinal detachment, diabetic retinopathy, orprogressive retinal disease;

5. have the presence of an active ocular infection (bacterial, viral or fungal),positive history of an ocular herpetic infection, or preauricularlymphadenopathy at any visit;

6. manifest signs or symptoms of clinically active allergic conjunctivitis ineither eye at the start of Visits 2, 3, or 4a (defined as a score of >0 foritching and/or >1 for conjunctival redness);

7. use any of the following disallowed medications during the period indicatedprior to Visit 2 and agree not to use disallowed medications throughout thestudy:

7 Days

• systemic or ocular H1 antihistamines, H1 antihistamine/mast-cell stabilizerdrug 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 maintainedfor at least 30 days prior to Visit 1 and will continue to be maintained forthe duration of the study. 14 Days

• inhaled, ocular, topical, or systemic corticosteroids or mast cellstabilizers; 45 Days

• depo-corticosteroids 2 Months

• immunosuppressive or cancer chemotherapeutic agents

Note: Currently marketed over-the counter anti-allergy eyedrops (i.e., antihistamine/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;

8. have any significant illness (for example, any autoimmune disease requiring therapy,or severe cardiovascular disease [including arrhythmias]) the Investigator feelscould be expected to interfere with the subject's safety or study parameters and/orput the subject at any unnecessary risk (includes but is not limited to poorlycontrolled hypertension or poorly controlled diabetes, a history of statusasthmaticus, organ transplants, a known history of persistent moderate or severeasthma, or a known history of moderate to severe allergic asthmatic reactions to anyof the study allergens);