Allergic Conjunctivitis
Conditions
Brief summary
To compare the safety and tolerability of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% combination ophthalmic solution versus its vehicle in healthy adult subjects and in pediatric subjects.
Detailed description
The study will consist of 4-5 study visits to compare the safety and tolerability of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% combination ophthalmic solution versus its vehicle in healthy adult subjects and in pediatric subjects with a history or family history of atopic disease (including allergic conjunctivitis). To characterize the plasma pharmacokinetics (PK) of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% combination ophthalmic solution following a single dose and 22-day twice daily (BID) topical ocular dosing in a subset of healthy adult subjects.
Interventions
DRUGBrimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
DRUGVehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% 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
5 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. be at least 5 years of age at Screening Visit or Visit 1 (if Screening and Visit 1 are done on the same day), of either sex and any race (a government issued ID and/or birth certificate will be verified at the time ICF is signed); 2. provide written informed consent and sign the the Health Insurance Portability and Accountability Act (HIPAA) form. Subjects who are at least 7 years of age and less than 18 years of age will need to sign an assent form. In addition, all subjects below the age of 18 years will be required to have both parents or legal guardian sign the informed consent. 3. be willing and able to follow all instructions and attend all study visits (and be accompanied by a parent/legal guardian if the subject is under the age of 18); 4. be able to self-administer eye drops satisfactorily or have a caregiver or parent/legal guardian (if applicable, for subjects less than 18 years of age) at home1 routinely available for this purpose. 5. for subjects less than 18 years of age, have either a history or family history of atopic disease (such as atopic dermatitis, asthma, allergic conjunctivitis/rhinitis, and atopic keratoconjunctivitis). 6. (if female and of childbearing potential) agree to have urine pregnancy testing performed at Visit 1 (must be negative) and at exit visit 2; must not be lactating; and must agree to use at least 1 medically acceptable form of birth control throughout the study duration and for at least 14 days prior to Visit 1 and 1 month after discontinuing investigational product. 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 1). 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). 7. (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 product (Visit 1). 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 discontinuing investigational product; 8. have ocular health within normal limits, including a calculated visual acuity of 0.3 logMAR or better in each eye as measured using an ETDRS chart. For subjects under 10 years old who are developmentally unable to use the ETDRS chart, a best attempt at visual acuity will be made using the LEA symbols or Visual Behavior. For subjects utilizing LEA symbols, Snellen equivalent units of 20/63 or better in both eyes will be required. Subjects utilizing Visual Behavior must have a passing score; 9. (for selected healthy adult subjects agreeing to undergo PK blood draws) have a body mass index (BMI) ≥18 and ≤34 lbs/in2 and a minimum body weight of 99 lbs; 10. (for selected healthy adult subjects agreeing to undergo PK blood draws) have suitable venous access for blood sampling.
Exclusion criteria
1. have known contraindications or sensitivities to the use of any of the investigational product medication or components; 2. have had ocular surgical intervention within 3 months prior to Visit 1 or during the study and/or a history of refractive surgery within the past 6 months; 3. have a known history of retinal detachment, diabetic retinopathy, or active retinal disease; 4. have the presence of an active ocular infection (bacterial, viral or fungal) or positive history of an ocular herpetic infection at any visit; 5. use any of the following disallowed medications during the period indicated prior to Visit 1 and during the study: 5 days * artificial tear products, eye whiteners (e.g., vasoconstrictors), ocular decongestants, ocular corticosteroids, ocular antihistamines, and any other topical ophthalmic agents; 14 days * any systemic medications which the investigator feels may confound study data or interfere with subject's study participation; 6\. have used contact lenses within 24 hours prior to each visit (Visit 1, 2, 3, and 4); 7\. have prior (within 7 days of beginning IP) or currently active significant illness that could compromise participation, in the opinion of the investigator; 8\. have prior (within 30 days of beginning investigational product) or anticipated concurrent use of an investigational product or device during the study period; 9\. have been randomized in study 909 or 910 conducted by Bausch & Lomb; 10\. be an employee or family member of employee at the investigative site; 11\. have an ocular or systemic condition or is in a situation that the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's study participation; 12\. have planned surgery (ocular or systemic) during the trial period or within 30 days after; 13\. have body weight below the 5th percentile for their age (subjects 12 years of age or younger only) (see Appendix 2); 14\. be a female who is currently pregnant, is planning a pregnancy, or lactating; 15\. have an abnormal blood pressure (defined as ≤ 90 or ≥ 160 (systolic) measured in mmHg or ≤ 60 or ≥ 100 (diastolic) measured in mmHg). For pediatric subjects, abnormal blood pressure is defined as ≥ 140 (systolic) measured in mmHg or ≥ 90 (diastolic) measured in mmHg; 16\. have an intraocular pressure (IOP) that is less than 5 mmHg or greater than 22 mmHg or have a normal IOP with a prior diagnosis/history of glaucoma at Visit 1; 17\. have symptoms associated with COVID-19 or have been in contact with someone diagnosed with COVID-19 within 14 days of the Screening Visit or Visit 1 (if Screening and Visit 1 are done on the same day); 18\. (for selected healthy adult subjects agreeing to undergo PK blood draws) have excessive consumption of caffeine- or xanthine-containing beverages (more than 4 cups or servings per day) within 48 hours prior to dosing at Visit 1 or for the duration of the study (see Appendix 6); 19\. (for selected healthy adult subjects agreeing to undergo PK blood draws) have a history of tobacco, nicotine, or nicotine-containing product use within 12 months prior to Visit 1; 20\. (for selected healthy adult subjects agreeing to undergo PK blood draws) have a history or current evidence of drug or alcohol abuse within 12 months prior to Visit 1; 21\. (for selected healthy adult subjects agreeing to undergo PK blood draws) have blood donation or equivalent blood loss of \>450 mL within 60 days prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Baseline up to Day 42 | TEAE is defined as any untoward medical occurrence or undesirable event(s) that begins or worsens following administration of the study drug, whether or not considered related to the treatment by the Investigator. A TEAE is considered serious if, in the view of the Investigator or Sponsor, it results in any of the following outcomes: death, a life-threatening TEAE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, an important medical event that jeopardized the participant and required medical intervention, or sight-threatening (possibly resulting in persistent or significant loss of vision) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drop Comfort Assessment as Assessed by the Participant | At dose installation, 30 seconds post dose installation, and 1-minute post dose installation on Day 1, Day 8 and Day 22 | Drop comfort assessment (0-10 unit scale in which a score of 0 denotes very comfortable and 10 is very uncomfortable) was performed by the participantsubjects ≥ 10 years of age |
| Plasma Concentration: Brimonidine | Pre-Instillation and 15 min, 30 min, 1 hr, 2hr and 4hrs post-instillation on Day 1 and on Day 22. | Blood samples will be collected to measure the concentration of brimonidine. Concentration values reported below the limit of quantification (BLQ) before the first quantifiable concentration or after the last quantifiable concentration were set to zero for concentration descriptive statistics. |
| Plasma Concentration: Ketotifen | Pre-Instillation and 15 min, 30 min, 1 hr, 2hr and 4hrs post-instillation on Day 1 and on Day 22. | Blood samples will be collected to measure the concentration of ketotifen. Concentration values reported below the quantification limit (BLQ) before the first quantifiable concentration or after the last quantifiable concentration were set to zero for concentration descriptive statistics. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo) | 340 |
| Vehicle Ophthalmic Solution Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution | 170 |
| Total | 510 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 2 |
| Overall Study | Discontinued | 4 | 4 |
| Overall Study | Lost to Follow-up | 14 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Vehicle Ophthalmic Solution | Total |
|---|---|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 19.71 | 38.7 years STANDARD_DEVIATION 19.99 | 38.5 years STANDARD_DEVIATION 19.79 |
| Age, Customized Between 18 and 64 years | 236 Participants | 111 Participants | 347 Participants |
| Age, Customized Greater or equal to 64 years | 38 Participants | 21 Participants | 59 Participants |
| Age, Customized Less or equal to 18 years | 66 Participants | 38 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 12 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 319 Participants | 158 Participants | 477 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 3 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 63 Participants | 28 Participants | 91 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) White | 253 Participants | 127 Participants | 380 Participants |
| Region of Enrollment United States | 340 participants | 170 participants | 510 participants |
| Sex: Female, Male Female | 216 Participants | 106 Participants | 322 Participants |
| Sex: Female, Male Male | 124 Participants | 64 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 340 | 0 / 170 |
| other Total, other adverse events | 32 / 340 | 9 / 170 |
| serious Total, serious adverse events | 0 / 340 | 1 / 170 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAE is defined as any untoward medical occurrence or undesirable event(s) that begins or worsens following administration of the study drug, whether or not considered related to the treatment by the Investigator. A TEAE is considered serious if, in the view of the Investigator or Sponsor, it results in any of the following outcomes: death, a life-threatening TEAE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, an important medical event that jeopardized the participant and required medical intervention, or sight-threatening (possibly resulting in persistent or significant loss of vision)
Time frame: Baseline up to Day 42
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One TEAE | 61 Participants |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One Ocular TEAE | 38 Participants |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One Non-Ocular TEAE | 28 Participants |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One Non-Ocular TE-SAE | 0 Participants |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with Treatment-Related TEAEs | 34 Participants |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with TEAEs by Maximum Severity (Mild) | 54 Participants |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with TEAEs by Maximum Severity (Moderate) | 7 Participants |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with TEAEs Leading to Early Treatment Discontinuation | 7 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with TEAEs Leading to Early Treatment Discontinuation | 3 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One TEAE | 19 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with Treatment-Related TEAEs | 7 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One Ocular TEAE | 10 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with TEAEs by Maximum Severity (Moderate) | 3 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One Non-Ocular TEAE | 9 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with TEAEs by Maximum Severity (Mild) | 16 Participants |
| Vehicle Ophthalmic Solution | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Subjects with at Least One Non-Ocular TE-SAE | 1 Participants |
Secondary
Drop Comfort Assessment as Assessed by the Participant
Drop comfort assessment (0-10 unit scale in which a score of 0 denotes very comfortable and 10 is very uncomfortable) was performed by the participantsubjects ≥ 10 years of age
Time frame: At dose installation, 30 seconds post dose installation, and 1-minute post dose installation on Day 1, Day 8 and Day 22
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 1 (Day 1) 30 seconds post instillation | 0.59 score on a scale | Standard Deviation 1.25 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 2 (Day 8) 1 minute post instillation | 0.30 score on a scale | Standard Deviation 0.906 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 2 (Day 8) immediately upon instillation | 1.13 score on a scale | Standard Deviation 1.665 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 3 (Day 22) immediately upon instillation | 0.93 score on a scale | Standard Deviation 1.512 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 1 (Day 1) 1 minute post instillation | 0.41 score on a scale | Standard Deviation 1.019 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 3 (Day 22) 30 seconds post instillation | 0.34 score on a scale | Standard Deviation 0.904 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 2 (Day 8) 30 seconds post instillation | 0.54 score on a scale | Standard Deviation 1.172 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 3 (Day 22) 1 minute post instillation | 0.15 score on a scale | Standard Deviation 0.558 |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 1 (Day 1) immediately upon instillation | 0.98 score on a scale | Standard Deviation 1.599 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 3 (Day 22) 1 minute post instillation | 0.18 score on a scale | Standard Deviation 0.706 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 1 (Day 1) immediately upon instillation | 0.56 score on a scale | Standard Deviation 1.19 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 1 (Day 1) 30 seconds post instillation | 0.38 score on a scale | Standard Deviation 0.959 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 1 (Day 1) 1 minute post instillation | 0.29 score on a scale | Standard Deviation 0.866 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 2 (Day 8) immediately upon instillation | 0.43 score on a scale | Standard Deviation 0.964 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 2 (Day 8) 30 seconds post instillation | 0.28 score on a scale | Standard Deviation 0.929 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 2 (Day 8) 1 minute post instillation | 0.21 score on a scale | Standard Deviation 0.758 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 3 (Day 22) immediately upon instillation | 0.50 score on a scale | Standard Deviation 1.109 |
| Vehicle Ophthalmic Solution | Drop Comfort Assessment as Assessed by the Participant | Visit 3 (Day 22) 30 seconds post instillation | 0.25 score on a scale | Standard Deviation 0.895 |
Secondary
Plasma Concentration: Brimonidine
Blood samples will be collected to measure the concentration of brimonidine. Concentration values reported below the limit of quantification (BLQ) before the first quantifiable concentration or after the last quantifiable concentration were set to zero for concentration descriptive statistics.
Time frame: Pre-Instillation and 15 min, 30 min, 1 hr, 2hr and 4hrs post-instillation on Day 1 and on Day 22.
Population: Pharmacokinetic population, subjects who provided at least one blood sample drawn post dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) Pre-instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 15 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 30 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 1 hr post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 2 hrs post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 4 hrs post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) Pre-instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 15 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 30 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 1 hr post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 2 hrs post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 4 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 2 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) Pre-instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) Pre-instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 15 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 1 hr post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 30 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 15 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 1 hr post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 4 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 2 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 3 (Day 22) 30 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Brimonidine | Visit 1 (Day 1) 4 hrs post instillation | 0 ng/ml |
Secondary
Plasma Concentration: Ketotifen
Blood samples will be collected to measure the concentration of ketotifen. Concentration values reported below the quantification limit (BLQ) before the first quantifiable concentration or after the last quantifiable concentration were set to zero for concentration descriptive statistics.
Time frame: Pre-Instillation and 15 min, 30 min, 1 hr, 2hr and 4hrs post-instillation on Day 1 and on Day 22.
Population: Pharmacokinetic population, subjects who provided at least one blood sample drawn post dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) Pre-instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 15 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 30 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 1 hr post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 2 hrs post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 4 hrs post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) Pre-instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 15 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 30 min post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 1 hr post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 2 hrs post instillation | 0 ng/ml |
| Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 4 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 2 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) Pre-instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) Pre-instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 15 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 1 hr post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 30 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 15 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 1 hr post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 4 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 2 hrs post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 3 (Day 22) 30 min post instillation | 0 ng/ml |
| Vehicle Ophthalmic Solution | Plasma Concentration: Ketotifen | Visit 1 (Day 1) 4 hrs post instillation | 0 ng/ml |