Trial Outcomes & Findings for Fixed Combination Brinzolamide 1%/Timolol 0.5% Versus Brinzolamide 1% + Timolol 0.5% in Open-Angle Glaucoma or Ocular Hypertension (NCT NCT01357616)

NCT ID: NCT01357616

Last Updated: 2014-04-10

Results Overview

Mean diurnal IOP change from baseline at Week 8 (ie, the subject IOP change from baseline averaged over the 9 AM, 11AM and 5 PM time points at Week 8) was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement..

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

328 participants

Primary outcome timeframe

Baseline, Week 8

Results posted on

2014-04-10

Participant Flow

Subjects were recruited from 13 study centers located in China.

This reporting group includes all enrolled subjects.

Participant milestones

Participant milestones
Measure
AZARGA
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
AZOPT + TIMOLOL
Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks.
Overall Study
STARTED
166
162
Overall Study
COMPLETED
156
153
Overall Study
NOT COMPLETED
10
9

Reasons for withdrawal

Reasons for withdrawal
Measure
AZARGA
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
AZOPT + TIMOLOL
Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks.
Overall Study
Adverse Event
1
1
Overall Study
Lost to Follow-up
4
3
Overall Study
Protocol Violation
0
2
Overall Study
Inadequate Control of IOP
1
2
Overall Study
Decision Unrelated to Adverse Event
3
1
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

Fixed Combination Brinzolamide 1%/Timolol 0.5% Versus Brinzolamide 1% + Timolol 0.5% in Open-Angle Glaucoma or Ocular Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
AZARGA
n=157 Participants
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
AZOPT + TIMOLOL
n=155 Participants
Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks.
Total
n=312 Participants
Total of all reporting groups
Age, Customized
<65 Years
148 participants
n=99 Participants
135 participants
n=107 Participants
283 participants
n=206 Participants
Age, Customized
≥65 Years
9 participants
n=99 Participants
20 participants
n=107 Participants
29 participants
n=206 Participants
Sex: Female, Male
Female
69 Participants
n=99 Participants
72 Participants
n=107 Participants
141 Participants
n=206 Participants
Sex: Female, Male
Male
88 Participants
n=99 Participants
83 Participants
n=107 Participants
171 Participants
n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Mean diurnal IOP change from baseline at Week 8 (ie, the subject IOP change from baseline averaged over the 9 AM, 11AM and 5 PM time points at Week 8) was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement..

Outcome measures

Outcome measures
Measure
AZARGA
n=157 Participants
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
AZOPT + Timolol
n=155 Participants
Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Mean Diurnal IOP Change From Baseline at Week 8
-6.84 millimeters mercury (mmHg)
Standard Deviation 3.557
-6.00 millimeters mercury (mmHg)
Standard Deviation 2.934

SECONDARY outcome

Timeframe: Baseline, Up to Week 8

Population: This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Mean IOP change from baseline at 9 AM was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.

Outcome measures

Outcome measures
Measure
AZARGA
n=157 Participants
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
AZOPT + Timolol
n=155 Participants
Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Mean IOP Change From Baseline at 9 AM
Change from baseline at Week 2
-6.9 mmHg
Standard Deviation 3.62
-6.5 mmHg
Standard Deviation 3.43
Mean IOP Change From Baseline at 9 AM
Change from baseline at Week 4
-7.3 mmHg
Standard Deviation 3.42
-6.4 mmHg
Standard Deviation 3.11
Mean IOP Change From Baseline at 9 AM
Change from baseline at Week 8
-6.7 mmHg
Standard Deviation 3.97
-6.2 mmHg
Standard Deviation 3.30

SECONDARY outcome

Timeframe: Baseline, Up to Week 8

Population: This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Mean IOP change from baseline at 11 AM was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.

Outcome measures

Outcome measures
Measure
AZARGA
n=157 Participants
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
AZOPT + Timolol
n=155 Participants
Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Mean IOP Change From Baseline at 11 AM
Change from baseline at Week 2
-7.5 mmHg
Standard Deviation 3.19
-6.8 mmHg
Standard Deviation 3.07
Mean IOP Change From Baseline at 11 AM
Change from baseline at Week 4
-7.6 mmHg
Standard Deviation 3.46
-6.8 mmHg
Standard Deviation 3.06
Mean IOP Change From Baseline at 11 AM
Change from baseline at Week 8
-7.4 mmHg
Standard Deviation 3.92
-6.5 mmHg
Standard Deviation 3.57

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Mean IOP change from baseline (5 PM) at Week 8 was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.

Outcome measures

Outcome measures
Measure
AZARGA
n=157 Participants
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
AZOPT + Timolol
n=155 Participants
Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Mean IOP Change From Baseline (5 PM) at Week 8
-6.3 mmHg
Standard Deviation 3.99
-5.1 mmHg
Standard Deviation 3.34

Adverse Events

AZARGA (Test Group)

Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths

AZOPT + TIMOLOL (Control Group)

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
AZARGA (Test Group)
n=165 participants at risk
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension
AZOPT + TIMOLOL (Control Group)
n=162 participants at risk
Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thymus
0.61%
1/165 • Number of events 1 • Adverse Events (AE) were collected for the duration of the study (2 years, 2 months). An AE was defined as any untoward medical occurrence in a subject who was administered a study treatment, regardless of causal relationship with the treatment.
Of the 328 enrolled, 1 subject did not receive study medication. This reporting group includes all subjects who were randomized and received study medication (327). Reports of AEs were obtained through solicited and spontaneous comments from the study subjects, and through observations by the study Investigator as outlined in the study protocol.
0.00%
0/162 • Adverse Events (AE) were collected for the duration of the study (2 years, 2 months). An AE was defined as any untoward medical occurrence in a subject who was administered a study treatment, regardless of causal relationship with the treatment.
Of the 328 enrolled, 1 subject did not receive study medication. This reporting group includes all subjects who were randomized and received study medication (327). Reports of AEs were obtained through solicited and spontaneous comments from the study subjects, and through observations by the study Investigator as outlined in the study protocol.

Other adverse events

Other adverse events
Measure
AZARGA (Test Group)
n=165 participants at risk
Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension
AZOPT + TIMOLOL (Control Group)
n=162 participants at risk
Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution
Investigations
Heart rate decreased
8.5%
14/165 • Adverse Events (AE) were collected for the duration of the study (2 years, 2 months). An AE was defined as any untoward medical occurrence in a subject who was administered a study treatment, regardless of causal relationship with the treatment.
Of the 328 enrolled, 1 subject did not receive study medication. This reporting group includes all subjects who were randomized and received study medication (327). Reports of AEs were obtained through solicited and spontaneous comments from the study subjects, and through observations by the study Investigator as outlined in the study protocol.
6.2%
10/162 • Adverse Events (AE) were collected for the duration of the study (2 years, 2 months). An AE was defined as any untoward medical occurrence in a subject who was administered a study treatment, regardless of causal relationship with the treatment.
Of the 328 enrolled, 1 subject did not receive study medication. This reporting group includes all subjects who were randomized and received study medication (327). Reports of AEs were obtained through solicited and spontaneous comments from the study subjects, and through observations by the study Investigator as outlined in the study protocol.

Additional Information

Mandy Ye, Head, Clinical Trial Management, Asia

Alcon Research, Ltd.

Phone: 1-888-451-3739

Results disclosure agreements

  • Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
  • Publication restrictions are in place

Restriction type: OTHER