Trial Outcomes & Findings for Evaluation of the Safety and Pharmacokinetics of Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution (NCT NCT05815758)
NCT ID: NCT05815758
Last Updated: 2025-07-10
Results Overview
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)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
512 participants
Primary outcome timeframe
Baseline up to Day 42
Results posted on
2025-07-10
Participant Flow
Participant milestones
| Measure |
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)
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
340
|
172
|
|
Overall Study
COMPLETED
|
309
|
158
|
|
Overall Study
NOT COMPLETED
|
31
|
14
|
Reasons for withdrawal
| Measure |
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)
|
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
|
|---|---|---|
|
Overall Study
Adverse Event
|
6
|
2
|
|
Overall Study
Lost to Follow-up
|
14
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
6
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Discontinued
|
4
|
4
|
Baseline Characteristics
Evaluation of the Safety and Pharmacokinetics of Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
Baseline characteristics by cohort
| Measure |
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
n=340 Participants
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
|
Vehicle Ophthalmic Solution
n=170 Participants
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution
|
Total
n=510 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.3 years
STANDARD_DEVIATION 19.71 • n=5 Participants
|
38.7 years
STANDARD_DEVIATION 19.99 • n=7 Participants
|
38.5 years
STANDARD_DEVIATION 19.79 • n=5 Participants
|
|
Age, Customized
Less or equal to 18 years
|
66 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
|
Age, Customized
Between 18 and 64 years
|
236 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
347 Participants
n=5 Participants
|
|
Age, Customized
Greater or equal to 64 years
|
38 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
216 Participants
n=5 Participants
|
106 Participants
n=7 Participants
|
322 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
124 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
188 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
21 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
319 Participants
n=5 Participants
|
158 Participants
n=7 Participants
|
477 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
16 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
63 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
253 Participants
n=5 Participants
|
127 Participants
n=7 Participants
|
380 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
340 participants
n=5 Participants
|
170 participants
n=7 Participants
|
510 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 42TEAE 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)
Outcome measures
| Measure |
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
n=340 Participants
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
|
Vehicle Ophthalmic Solution
n=170 Participants
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with at Least One TEAE
|
61 Participants
|
19 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with at Least One Ocular TEAE
|
38 Participants
|
10 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with at Least One Non-Ocular TEAE
|
28 Participants
|
9 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with at Least One Non-Ocular TE-SAE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with Treatment-Related TEAEs
|
34 Participants
|
7 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with TEAEs by Maximum Severity (Mild)
|
54 Participants
|
16 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with TEAEs by Maximum Severity (Moderate)
|
7 Participants
|
3 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with TEAEs Leading to Early Treatment Discontinuation
|
7 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: At dose installation, 30 seconds post dose installation, and 1-minute post dose installation on Day 1, Day 8 and Day 22Drop 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
Outcome measures
| Measure |
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
n=340 Participants
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
|
Vehicle Ophthalmic Solution
n=170 Participants
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% 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
|
0.56 score on a scale
Standard Deviation 1.190
|
|
Drop Comfort Assessment as Assessed by the Participant
Visit 1 (Day 1) 30 seconds post instillation
|
0.59 score on a scale
Standard Deviation 1.250
|
0.38 score on a scale
Standard Deviation 0.959
|
|
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
|
0.29 score on a scale
Standard Deviation 0.866
|
|
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
|
0.43 score on a scale
Standard Deviation 0.964
|
|
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
|
0.28 score on a scale
Standard Deviation 0.929
|
|
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
|
0.21 score on a scale
Standard Deviation 0.758
|
|
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
|
0.50 score on a scale
Standard Deviation 1.109
|
|
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
|
0.25 score on a scale
Standard Deviation 0.895
|
|
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
|
0.18 score on a scale
Standard Deviation 0.706
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
n=20 Participants
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
|
Vehicle Ophthalmic Solution
n=5 Participants
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution
|
|---|---|---|
|
Plasma Concentration: Brimonidine
Visit 1 (Day 1) Pre-instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 1 (Day 1) 15 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 1 (Day 1) 30 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 1 (Day 1) 1 hr post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 1 (Day 1) 2 hrs post instillation
|
0 ng/ml
Interval 0.0 to 28.1
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 1 (Day 1) 4 hrs post instillation
|
0 ng/ml
Interval 0.0 to 24.2
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 3 (Day 22) Pre-instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 3 (Day 22) 15 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 3 (Day 22) 30 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 3 (Day 22) 1 hr post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 3 (Day 22) 2 hrs post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Brimonidine
Visit 3 (Day 22) 4 hrs post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
n=20 Participants
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
|
Vehicle Ophthalmic Solution
n=5 Participants
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution
|
|---|---|---|
|
Plasma Concentration: Ketotifen
Visit 3 (Day 22) 1 hr post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 3 (Day 22) 30 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 1 (Day 1) Pre-instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 1 (Day 1) 15 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 1 (Day 1) 30 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 1 (Day 1) 1 hr post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 1 (Day 1) 2 hrs post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 1 (Day 1) 4 hrs post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 3 (Day 22) Pre-instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 3 (Day 22) 15 min post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 3 (Day 22) 2 hrs post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
|
Plasma Concentration: Ketotifen
Visit 3 (Day 22) 4 hrs post instillation
|
0 ng/ml
Interval 0.0 to 0.0
|
0 ng/ml
Interval 0.0 to 0.0
|
Adverse Events
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
Serious events: 0 serious events
Other events: 32 other events
Deaths: 0 deaths
Vehicle Ophthalmic Solution
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
n=340 participants at risk
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
|
Vehicle Ophthalmic Solution
n=170 participants at risk
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution
|
|---|---|---|
|
General disorders
Acute Cholecystitis
|
0.00%
0/340 • Assessed throughout the study approximately 6-10 weeks
|
0.59%
1/170 • Number of events 1 • Assessed throughout the study approximately 6-10 weeks
|
Other adverse events
| Measure |
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution
n=340 participants at risk
Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo): Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Ophthalmic Solution (Combo)
|
Vehicle Ophthalmic Solution
n=170 participants at risk
Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution: Vehicle of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution
|
|---|---|---|
|
Eye disorders
Conjunctival Hyperaemia
|
1.5%
5/340 • Number of events 5 • Assessed throughout the study approximately 6-10 weeks
|
1.2%
2/170 • Number of events 2 • Assessed throughout the study approximately 6-10 weeks
|
|
Eye disorders
General disorders and administration site conditions
|
3.8%
13/340 • Number of events 13 • Assessed throughout the study approximately 6-10 weeks
|
1.2%
2/170 • Number of events 2 • Assessed throughout the study approximately 6-10 weeks
|
|
Eye disorders
Instillation site irritation
|
3.8%
13/340 • Number of events 13 • Assessed throughout the study approximately 6-10 weeks
|
1.2%
2/170 • Number of events 2 • Assessed throughout the study approximately 6-10 weeks
|
|
Eye disorders
Eye disorders
|
5.0%
17/340 • Number of events 17 • Assessed throughout the study approximately 6-10 weeks
|
1.8%
3/170 • Number of events 3 • Assessed throughout the study approximately 6-10 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place