Allergic Conjunctivitis
Conditions
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:
Interventions
DRUGBrimonidine tartrate 0.025%/ketotifen fumarate 0.035%
combination ophthalmic solution
ophthalmic Solution
DRUGKetotifen Fumarate 0.035%
ophthalmic Solution
DRUGVehicle
ophthalmic Solution
Sponsors
Bausch & Lomb Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
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 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; 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 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); 5. (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. 6. 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; 7. 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; 8. 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; 9. 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; 10. 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: 1. have known contraindications or sensitivities to the use of any of the investigational product(s) or their components; 2. 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); 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 to enrollment (Visit 4a); 4. have a known history of retinal detachment, diabetic retinopathy, or progressive retinal disease; 5. 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; 6. 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); 7. 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 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 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);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Itching | Assessed at Visit 4b on day 1 (duration of action CAC at 8 hours post-instillation of study medication) and Visit 5 on day 15 (onset of action CAC at 15 minutes post-instillation of study medication). | Ocular itching score (measured on a 0-4 unit scale, allowing half-unit increments; average score of the subject's two eyes) assessed by the subjects at 3 (±1), 5 (±1), and 7 (±1) minutes post-CAC. |
| Conjunctival Redness | Assessed at Visit 4b on day 1 (duration of action CAC at 8 hours post-instillation of study medication) and Visit 5 on day 15 (onset of action CAC at 15 minutes post-instillation of study medication). | Conjunctival redness score (measured on a 0-4unit scale, allowing half-unit increments; average score of the subject's two eyes) assessed by investigator at 7 (±1), 15 (±1), and 20 (±1) minutes post-CAC. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination Brimonidine tartrate 0.025% / ketotifen fumarate 0.035% ophthalmic solution administered bilaterally | 47 |
| Ketotifen Fumarate Ketotifen fumarate ophthalmic solution 0.035% administered bilaterally | 48 |
| Brimonidine Tartrate Brimonidine tartrate ophthalmic solution 0.025% administered bilaterally | 47 |
| Vehicle Vehicle ophthalmic solution administered bilaterally | 46 |
| Total | 188 |
Baseline characteristics
| Characteristic | Combination | Ketotifen Fumarate | Brimonidine Tartrate | Vehicle | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 16.9 | 49.3 years STANDARD_DEVIATION 14.19 | 45.9 years STANDARD_DEVIATION 17.74 | 49.9 years STANDARD_DEVIATION 12.18 | 48.1 years STANDARD_DEVIATION 15.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 6 Participants | 2 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 43 Participants | 41 Participants | 44 Participants | 170 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 34 Participants | 30 Participants | 32 Participants | 26 Participants | 122 Participants |
| Sex: Female, Male Male | 13 Participants | 18 Participants | 15 Participants | 20 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 48 | 0 / 47 | 0 / 46 |
| other Total, other adverse events | 3 / 47 | 6 / 48 | 6 / 47 | 4 / 46 |
| serious Total, serious adverse events | 0 / 47 | 0 / 48 | 0 / 47 | 0 / 46 |
Outcome results
Primary
Conjunctival Redness
Conjunctival redness score (measured on a 0-4unit scale, allowing half-unit increments; average score of the subject's two eyes) assessed by investigator at 7 (±1), 15 (±1), and 20 (±1) minutes post-CAC.
Time frame: Assessed at Visit 4b on day 1 (duration of action CAC at 8 hours post-instillation of study medication) and Visit 5 on day 15 (onset of action CAC at 15 minutes post-instillation of study medication).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination | Conjunctival Redness | Visit 5, 15 min Post-CAC | 0.765 score on a scale | Standard Error 0.1043 |
| Combination | Conjunctival Redness | Visit 4b, 15 min Post-CAC | 1.617 score on a scale | Standard Error 0.1204 |
| Combination | Conjunctival Redness | Visit 5, 20 min Post-CAC | 0.735 score on a scale | Standard Error 0.1012 |
| Combination | Conjunctival Redness | Visit 4b, 20 min Post-CAC | 1.649 score on a scale | Standard Error 0.1165 |
| Combination | Conjunctival Redness | Visit 5, 7 min Post-CAC | 0.591 score on a scale | Standard Error 0.0846 |
| Combination | Conjunctival Redness | Visit 4b, 7 min Post-CAC | 1.372 score on a scale | Standard Error 0.1088 |
| Ketotifen Fumarate | Conjunctival Redness | Visit 4b, 20 min Post-CAC | 2.146 score on a scale | Standard Error 0.0953 |
| Ketotifen Fumarate | Conjunctival Redness | Visit 4b, 7 min Post-CAC | 1.844 score on a scale | Standard Error 0.0895 |
| Ketotifen Fumarate | Conjunctival Redness | Visit 5, 15 min Post-CAC | 1.662 score on a scale | Standard Error 0.1036 |
| Ketotifen Fumarate | Conjunctival Redness | Visit 5, 7 min Post-CAC | 1.393 score on a scale | Standard Error 0.0944 |
| Ketotifen Fumarate | Conjunctival Redness | Visit 5, 20 min Post-CAC | 1.727 score on a scale | Standard Error 0.1088 |
| Ketotifen Fumarate | Conjunctival Redness | Visit 4b, 15 min Post-CAC | 2.130 score on a scale | Standard Error 0.0939 |
| Brimonidine Tartrate | Conjunctival Redness | Visit 5, 20 min Post-CAC | 1.021 score on a scale | Standard Error 0.1343 |
| Brimonidine Tartrate | Conjunctival Redness | Visit 4b, 15 min Post-CAC | 2.069 score on a scale | Standard Error 0.1189 |
| Brimonidine Tartrate | Conjunctival Redness | Visit 5, 7 min Post-CAC | 1.005 score on a scale | Standard Error 0.13 |
| Brimonidine Tartrate | Conjunctival Redness | Visit 4b, 20 min Post-CAC | 1.984 score on a scale | Standard Error 0.1296 |
| Brimonidine Tartrate | Conjunctival Redness | Visit 4b, 7 min Post-CAC | 1.883 score on a scale | Standard Error 0.1083 |
| Brimonidine Tartrate | Conjunctival Redness | Visit 5, 15 min Post-CAC | 1.069 score on a scale | Standard Error 0.1338 |
| Vehicle | Conjunctival Redness | Visit 4b, 20 min Post-CAC | 2.315 score on a scale | Standard Error 0.0961 |
| Vehicle | Conjunctival Redness | Visit 4b, 7 min Post-CAC | 2.155 score on a scale | Standard Error 0.085 |
| Vehicle | Conjunctival Redness | Visit 4b, 15 min Post-CAC | 2.321 score on a scale | Standard Error 0.0934 |
| Vehicle | Conjunctival Redness | Visit 5, 20 min Post-CAC | 2.238 score on a scale | Standard Error 0.1182 |
| Vehicle | Conjunctival Redness | Visit 5, 7 min Post-CAC | 2.052 score on a scale | Standard Error 0.1143 |
| Vehicle | Conjunctival Redness | Visit 5, 15 min Post-CAC | 2.268 score on a scale | Standard Error 0.1111 |
Primary
Ocular Itching
Ocular itching score (measured on a 0-4 unit scale, allowing half-unit increments; average score of the subject's two eyes) assessed by the subjects at 3 (±1), 5 (±1), and 7 (±1) minutes post-CAC.
Time frame: Assessed at Visit 4b on day 1 (duration of action CAC at 8 hours post-instillation of study medication) and Visit 5 on day 15 (onset of action CAC at 15 minutes post-instillation of study medication).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination | Ocular Itching | Visit 4b, 3 min Post-CAC | 1.176 score on a scale | Standard Error 0.1464 |
| Combination | Ocular Itching | Visit 4b, 5 min Post-CAC | 1.287 score on a scale | Standard Error 0.1507 |
| Combination | Ocular Itching | Visit 4b, 7 min Post-CAC | 1.181 score on a scale | Standard Error 0.1462 |
| Combination | Ocular Itching | Visit 5, 3 min Post-CAC | 0.495 score on a scale | Standard Error 0.0918 |
| Combination | Ocular Itching | Visit 5, 5 min Post-CAC | 0.601 score on a scale | Standard Error 0.093 |
| Combination | Ocular Itching | Visit 5, 7 min Post-CAC | 0.618 score on a scale | Standard Error 0.1083 |
| Ketotifen Fumarate | Ocular Itching | Visit 5, 7 min Post-CAC | 0.972 score on a scale | Standard Error 0.1548 |
| Ketotifen Fumarate | Ocular Itching | Visit 5, 3 min Post-CAC | 0.594 score on a scale | Standard Error 0.1296 |
| Ketotifen Fumarate | Ocular Itching | Visit 4b, 3 min Post-CAC | 1.708 score on a scale | Standard Error 0.1487 |
| Ketotifen Fumarate | Ocular Itching | Visit 4b, 7 min Post-CAC | 1.656 score on a scale | Standard Error 0.1532 |
| Ketotifen Fumarate | Ocular Itching | Visit 4b, 5 min Post-CAC | 1.688 score on a scale | Standard Error 0.1519 |
| Ketotifen Fumarate | Ocular Itching | Visit 5, 5 min Post-CAC | 0.791 score on a scale | Standard Error 0.135 |
| Brimonidine Tartrate | Ocular Itching | Visit 4b, 5 min Post-CAC | 2.638 score on a scale | Standard Error 0.1155 |
| Brimonidine Tartrate | Ocular Itching | Visit 4b, 7 min Post-CAC | 2.644 score on a scale | Standard Error 0.1249 |
| Brimonidine Tartrate | Ocular Itching | Visit 5, 3 min Post-CAC | 1.915 score on a scale | Standard Error 0.1307 |
| Brimonidine Tartrate | Ocular Itching | Visit 5, 7 min Post-CAC | 1.920 score on a scale | Standard Error 0.1394 |
| Brimonidine Tartrate | Ocular Itching | Visit 5, 5 min Post-CAC | 1.973 score on a scale | Standard Error 0.1255 |
| Brimonidine Tartrate | Ocular Itching | Visit 4b, 3 min Post-CAC | 2.426 score on a scale | Standard Error 0.133 |
| Vehicle | Ocular Itching | Visit 5, 5 min Post-CAC | 2.345 score on a scale | Standard Error 0.1378 |
| Vehicle | Ocular Itching | Visit 5, 7 min Post-CAC | 2.358 score on a scale | Standard Error 0.1221 |
| Vehicle | Ocular Itching | Visit 4b, 5 min Post-CAC | 2.712 score on a scale | Standard Error 0.1427 |
| Vehicle | Ocular Itching | Visit 5, 3 min Post-CAC | 2.070 score on a scale | Standard Error 0.1319 |
| Vehicle | Ocular Itching | Visit 4b, 3 min Post-CAC | 2.362 score on a scale | Standard Error 0.1512 |
| Vehicle | Ocular Itching | Visit 4b, 7 min Post-CAC | 2.755 score on a scale | Standard Error 0.139 |