Trial Outcomes & Findings for Nebivolol 0.5, 1.0, or Timolol 0.5 Suspension Compared to Timolol 0.5 Solution to Treat Glaucoma/Ocular Hypertension (NCT NCT04910100)
NCT ID: NCT04910100
Last Updated: 2024-04-17
Results Overview
Measured utilizing a calibrated Goldmann tonometer; two consecutive IOP measurements of each eye will be performed. If the 2 measurements differ by more than 2 mm Hg, a third measurement will be taken. The primary efficacy analysis will be the between-group comparison of the mean IOP values in the study eye at 10AM, 2 hours postdose, and 4PM, at each of the Visit 4/Day 15, Visit 5/Day 42, and Visit 6/Day 84 visits (ie, a total of 9 between-group comparisons). A hierarchical analysis will be conducted to compare each of the investigational products against the comparator, timolol 0.5% ophthalmic solution, as follows: (1) nebivolol 1% ophthalmic suspension, (2) nebivolol 0.5% ophthalmic suspension, and (3) timolol ophthalmic suspension.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
226 participants
Primary outcome timeframe
Over 84 days
Results posted on
2024-04-17
Participant Flow
A total of 226 subjects were recruited and treated at 19 clinical investigation sites over a 12 month period commencing on 15 April 2021 and completing on 31 March 2022
Following successful completion of screening based on protocol specified inclusion and exclusion criteria and a wash out period of up to 28 days subjects were treated with investigational medication twice daily for 84 days.
Participant milestones
| Measure |
Nebivolol Ophthalmic Suspension 1 Percent
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 1 Percent: 1 drop instilled into each eye twice daily
|
Nebivolol Ophthalmic Suspension 0.5 Percent
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Suspension 0.5 Percent
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Solution 0.5 Percent
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Solution 0.5 Percent: 1 drop instilled into each eye twice daily
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
54
|
58
|
56
|
58
|
|
Overall Study
COMPLETED
|
49
|
51
|
55
|
54
|
|
Overall Study
NOT COMPLETED
|
5
|
7
|
1
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nebivolol 0.5, 1.0, or Timolol 0.5 Suspension Compared to Timolol 0.5 Solution to Treat Glaucoma/Ocular Hypertension
Baseline characteristics by cohort
| Measure |
Nebivolol Ophthalmic Suspension 1 Percent
n=54 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 1 Percent: 1 drop instilled into each eye twice daily
|
Nebivolol Ophthalmic Suspension 0.5 Percent
n=58 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Suspension 0.5 Percent
n=56 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Solution 0.5 Percent
n=58 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Solution 0.5 Percent: 1 drop instilled into each eye twice daily
|
Total
n=226 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
64.7 years
STANDARD_DEVIATION 13.92 • n=5 Participants
|
67.6 years
STANDARD_DEVIATION 10.38 • n=7 Participants
|
65.6 years
STANDARD_DEVIATION 12.71 • n=5 Participants
|
66.0 years
STANDARD_DEVIATION 11.6 • n=4 Participants
|
66.0 years
STANDARD_DEVIATION 12.15 • n=21 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
137 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
89 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
43 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
43 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
47 Participants
n=4 Participants
|
183 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
16 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
74 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
149 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
54 participants
n=5 Participants
|
58 participants
n=7 Participants
|
56 participants
n=5 Participants
|
58 participants
n=4 Participants
|
226 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Over 84 daysPopulation: The analysis is performed at 9 different time points and compared to baseline (Visit 3 - Day 1), hence, the numbers analyzed at each time point differs from the overall number due to drop outs
Measured utilizing a calibrated Goldmann tonometer; two consecutive IOP measurements of each eye will be performed. If the 2 measurements differ by more than 2 mm Hg, a third measurement will be taken. The primary efficacy analysis will be the between-group comparison of the mean IOP values in the study eye at 10AM, 2 hours postdose, and 4PM, at each of the Visit 4/Day 15, Visit 5/Day 42, and Visit 6/Day 84 visits (ie, a total of 9 between-group comparisons). A hierarchical analysis will be conducted to compare each of the investigational products against the comparator, timolol 0.5% ophthalmic solution, as follows: (1) nebivolol 1% ophthalmic suspension, (2) nebivolol 0.5% ophthalmic suspension, and (3) timolol ophthalmic suspension.
Outcome measures
| Measure |
Nebivolol Ophthalmic Suspension 1 Percent
n=52 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 1 Percent: 1 drop instilled into each eye twice daily
|
Nebivolol Ophthalmic Suspension 0.5 Percent
n=56 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Suspension 0.5 Percent
n=55 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Solution 0.5 Percent
n=57 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Solution 0.5 Percent: 1 drop instilled into each eye twice daily
|
|---|---|---|---|---|
|
Intraocular Pressure Over 84 Days
Visit 4 - Day 15 - 8 am
|
22.0 mmHg
Interval 21.1 to 23.0
|
22.5 mmHg
Interval 21.6 to 23.4
|
18.8 mmHg
Interval 17.9 to 19.7
|
19.4 mmHg
Interval 18.5 to 20.3
|
|
Intraocular Pressure Over 84 Days
Visit 4 - Day 15 - 10 am
|
20.4 mmHg
Interval 19.5 to 21.2
|
21.1 mmHg
Interval 20.3 to 21.9
|
17.7 mmHg
Interval 16.9 to 18.5
|
17.9 mmHg
Interval 17.1 to 18.8
|
|
Intraocular Pressure Over 84 Days
Visit 4 - Day 15 - 4 pm
|
19.8 mmHg
Interval 18.9 to 20.6
|
20.6 mmHg
Interval 19.8 to 21.4
|
18.2 mmHg
Interval 17.4 to 19.0
|
18.4 mmHg
Interval 17.6 to 19.2
|
|
Intraocular Pressure Over 84 Days
Visit 5 - Day 42 - 8 am
|
21.8 mmHg
Interval 20.8 to 22.8
|
21.7 mmHg
Interval 20.7 to 22.7
|
19.0 mmHg
Interval 18.1 to 20.0
|
19.3 mmHg
Interval 18.4 to 20.3
|
|
Intraocular Pressure Over 84 Days
Visit 5 - Day 42 - 10 am
|
20.2 mmHg
Interval 19.3 to 21.2
|
20.3 mmHg
Interval 19.4 to 21.3
|
17.8 mmHg
Interval 16.9 to 18.7
|
18.3 mmHg
Interval 17.4 to 19.2
|
|
Intraocular Pressure Over 84 Days
Visit 5 - Day 42 - 4 pm
|
20.1 mmHg
Interval 19.1 to 21.0
|
20.5 mmHg
Interval 19.5 to 21.5
|
18.4 mmHg
Interval 17.4 to 19.3
|
18.3 mmHg
Interval 17.4 to 19.2
|
|
Intraocular Pressure Over 84 Days
Visit 6 - Day 84 - 8 am
|
21.2 mmHg
Interval 20.3 to 22.2
|
21.3 mmHg
Interval 20.4 to 22.2
|
18.5 mmHg
Interval 17.6 to 19.4
|
19.4 mmHg
Interval 18.6 to 20.3
|
|
Intraocular Pressure Over 84 Days
Visit 6 - Day 84 -10 am
|
20.1 mmHg
Interval 19.3 to 20.9
|
20.2 mmHg
Interval 19.4 to 21.0
|
17.9 mmHg
Interval 17.1 to 18.6
|
18.6 mmHg
Interval 17.8 to 19.3
|
|
Intraocular Pressure Over 84 Days
Visit 6 - Day 84 - 4 pm
|
19.8 mmHg
Interval 19.0 to 20.6
|
20.1 mmHg
Interval 19.3 to 20.8
|
18.1 mmHg
Interval 17.4 to 18.9
|
18.6 mmHg
Interval 17.9 to 19.4
|
SECONDARY outcome
Timeframe: Day 15: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 42: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 84: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutesPopulation: Study eye for the Per Protocol population
Change from baseline (Visit 3/Qualification/Baseline) in the average of the 3 daily IOP measurements at Day 15, Day 42, and Day 84
Outcome measures
| Measure |
Nebivolol Ophthalmic Suspension 1 Percent
n=52 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 1 Percent: 1 drop instilled into each eye twice daily
|
Nebivolol Ophthalmic Suspension 0.5 Percent
n=56 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Suspension 0.5 Percent
n=55 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Solution 0.5 Percent
n=57 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Solution 0.5 Percent: 1 drop instilled into each eye twice daily
|
|---|---|---|---|---|
|
Intraocular Pressure: Change From Baseline in Diurnal IOP at Each Visit
Visit 4 - Day 15
|
-3.1 mmHg
Standard Error 0.44
|
-2.2 mmHg
Standard Error 0.42
|
-5.5 mmHg
Standard Error 0.42
|
-5.2 mmHg
Standard Error 0.41
|
|
Intraocular Pressure: Change From Baseline in Diurnal IOP at Each Visit
Visit 5 - Day 42
|
-3.1 mmHg
Standard Error 0.48
|
-2.8 mmHg
Standard Error 0.47
|
-5.4 mmHg
Standard Error 0.46
|
-5.2 mmHg
Standard Error 0.46
|
|
Intraocular Pressure: Change From Baseline in Diurnal IOP at Each Visit
Visit 6 - Day 84
|
-3.5 mmHg
Standard Error 0.38
|
-3.2 mmHg
Standard Error 0.37
|
-5.6 mmHg
Standard Error 0.36
|
-4.9 mmHg
Standard Error 0.36
|
SECONDARY outcome
Timeframe: Day 15: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 42: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 84: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutesPopulation: Study Eye in the Per Protocol population
Time-matched change from baseline (Visit 3/Qualification/Baseline) in the 3 daily IOP measurements at Day 15, Day 42 and Day 84
Outcome measures
| Measure |
Nebivolol Ophthalmic Suspension 1 Percent
n=52 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 1 Percent: 1 drop instilled into each eye twice daily
|
Nebivolol Ophthalmic Suspension 0.5 Percent
n=56 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Suspension 0.5 Percent
n=55 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Solution 0.5 Percent
n=57 Participants
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Solution 0.5 Percent: 1 drop instilled into each eye twice daily
|
|---|---|---|---|---|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 4 - Day 15 - 8 am
|
-3.0 mmHg
Standard Error 0.49
|
-2.5 mmHg
Standard Error 0.47
|
-6.1 mmHg
Standard Error 0.47
|
-5.8 mmHg
Standard Error 0.47
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 5 - Day 42 - 8 am
|
-3.3 mmHg
Standard Error 0.52
|
-3.4 mmHg
Standard Error 0.50
|
-5.9 mmHg
Standard Error 0.50
|
-5.8 mmHg
Standard Error 0.49
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 6 - Day 84 - 8 am
|
-3.8 mmHg
Standard Error 0.48
|
-3.7 mmHg
Standard Error 0.47
|
-6.5 mmHg
Standard Error 0.45
|
-5.7 mmHg
Standard Error 0.45
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 4 - Day 15 - 10am
|
-3.2 mmHg
Standard Error 0.46
|
-2.3 mmHg
Standard Error 0.45
|
-5.9 mmHg
Standard Error 0.45
|
-5.5 mmHg
Standard Error 0.44
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 5 - Day 42 - 10 am
|
-3.3 mmHg
Standard Error 0.50
|
-3.1 mmHg
Standard Error 0.49
|
-5.8 mmHg
Standard Error 0.48
|
-5.2 mmHg
Standard Error 0.47
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 6 - Day 84 - 10 am
|
-3.4 mmHg
Standard Error 0.43
|
-3.2 mmHg
Standard Error 0.41
|
-5.7 mmHg
Standard Error 0.40
|
-4.9 mmHg
Standard Error 0.40
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 4 - Day 15 - 4 pm
|
-2.9 mmHg
Standard Error 0.43
|
-2.4 mmHg
Standard Error 0.42
|
-4.6 mmHg
Standard Error 0.42
|
-4.4 mmHg
Standard Error 0.41
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 5 - Day 42 - 4 pm
|
-2.7 mmHg
Standard Error 0.50
|
-2.5 mmHg
Standard Error 0.49
|
-4.4 mmHg
Standard Error 0.48
|
-4.5 mmHg
Standard Error 0.48
|
|
Intraocular Pressure: Change From Baseline at All Time Points at Each Visit
Visit 6 - Day 42 - 4 pm
|
-3.0 mmHg
Standard Error 0.44
|
-2.9 mmHg
Standard Error 0.43
|
-4.7 mmHg
Standard Error 0.41
|
-4.1 mmHg
Standard Error 0.41
|
Adverse Events
Nebivolol Ophthalmic Suspension 1 Percent
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Nebivolol Ophthalmic Suspension 0.5 Percent
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Timolol Ophthalmic Suspension 0.5 Percent
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Timolol Ophthalmic Solution 0.5 Percent
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Nebivolol Ophthalmic Suspension 1 Percent
n=54 participants at risk
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 1 Percent: 1 drop instilled into each eye twice daily
|
Nebivolol Ophthalmic Suspension 0.5 Percent
n=58 participants at risk
Administered twice daily to both eyes for 84 days (12 weeks)
Nebivolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Suspension 0.5 Percent
n=56 participants at risk
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Suspension 0.5 Percent: 1 drop instilled into each eye twice daily
|
Timolol Ophthalmic Solution 0.5 Percent
n=58 participants at risk
Administered twice daily to both eyes for 84 days (12 weeks)
Timolol Ophthalmic Solution 0.5 Percent: 1 drop instilled into each eye twice daily
|
|---|---|---|---|---|
|
Eye disorders
Instillation site pain
|
1.9%
1/54 • Number of events 1 • 84 days
|
0.00%
0/58 • 84 days
|
7.1%
4/56 • Number of events 4 • 84 days
|
6.9%
4/58 • Number of events 4 • 84 days
|
|
Eye disorders
Instillation site reaction
|
7.4%
4/54 • Number of events 4 • 84 days
|
0.00%
0/58 • 84 days
|
1.8%
1/56 • Number of events 1 • 84 days
|
0.00%
0/58 • 84 days
|
|
Eye disorders
Conjunctival hyperemia
|
0.00%
0/54 • 84 days
|
0.00%
0/58 • 84 days
|
3.6%
2/56 • Number of events 2 • 84 days
|
0.00%
0/58 • 84 days
|
|
Eye disorders
Eye pain
|
0.00%
0/54 • 84 days
|
3.4%
2/58 • Number of events 2 • 84 days
|
0.00%
0/56 • 84 days
|
0.00%
0/58 • 84 days
|
|
Eye disorders
Instillation site discomfort
|
0.00%
0/54 • 84 days
|
0.00%
0/58 • 84 days
|
0.00%
0/56 • 84 days
|
3.4%
2/58 • Number of events 2 • 84 days
|
|
Eye disorders
Intraocular pressure increased
|
3.7%
2/54 • Number of events 2 • 84 days
|
0.00%
0/58 • 84 days
|
0.00%
0/56 • 84 days
|
0.00%
0/58 • 84 days
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/54 • 84 days
|
3.4%
2/58 • Number of events 2 • 84 days
|
0.00%
0/56 • 84 days
|
0.00%
0/58 • 84 days
|
|
Nervous system disorders
Headache
|
0.00%
0/54 • 84 days
|
3.4%
2/58 • Number of events 2 • 84 days
|
0.00%
0/56 • 84 days
|
0.00%
0/58 • 84 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place