SIMBRINZA® Suspension BID as an Adjunctive to Prostaglandin Analogue (PGA)

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02419508
• Collaborator: (none)
• Enrollment: 290
• Location: 1
• Arms: 2
• Actual Duration (Months): 30.7
• Patients Per Site Per Month: 9.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the additive intraocular pressure (IOP) lowering effect of brinzolamide 1%/brimonidine 0.2% (dosed twice per day (BID)) when added to a prostaglandin analogue (PGA) in subjects with open-angle glaucoma or ocular hypertension.

Condition or Disease	Intervention/Treatment	Phase
Open-Angle Glaucoma; Ocular Hypertension	Drug: Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension; Drug: Brinz/brim vehicle; Drug: Prostaglandin analogue	Phase 4

Detailed Description

This study consisted of 2 sequential phases: Screening/Eligibility Phase, followed by a Masked Treatment Phase (Phase II). Subjects were assigned into one of 3 PGA therapy groups for the duration of the study, based upon commercial availability.

Study Design

• Study Type: Interventional
• Actual Enrollment: 290 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Additive Effect of Twice Daily Brinzolamide 1%/Brimonidine 0.2% Fixed Dose Combination as an Adjunctive Therapy to a Prostaglandin Analogue
• Actual Study Start Date: Aug 7, 2015
• Actual Primary Completion Date: Feb 27, 2018
• Actual Study Completion Date: Feb 27, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SIMBRINZA + PGA Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Drug: Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension; Other Names: SIMBRINZA® suspension ; Drug: Prostaglandin analogue; Other Names: TRAVATAN® PQ (Travoprost ophthalmic solution with PQ, 0.004%) LUMIGAN® (Bimatoprost ophthalmic solution, 0.01%) XALATAN® (Latanoprost ophthalmic solution, 0.005%)
Other: Vehicle + PGA Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Drug: Brinz/brim vehicle; Inactive ingredients used as a placebo for masking purposes; Drug: Prostaglandin analogue; Other Names: TRAVATAN® PQ (Travoprost ophthalmic solution with PQ, 0.004%) LUMIGAN® (Bimatoprost ophthalmic solution, 0.01%) XALATAN® (Latanoprost ophthalmic solution, 0.005%)

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6 [Baseline, Week 6]

   IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

Secondary Outcome Measures

1. Mean Diurnal IOP at Week 6 [Week 6]

   IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.

2. Mean Percentage Change From Baseline in Diurnal IOP at Week 6 [Baseline, Week 6]

   IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

3. Mean Change From Baseline in IOP at 11:00 at Week 6 [Baseline, Week 6]

   IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

4. Mean Percentage Change From Baseline in IOP at 11:00 at Week 6 [Baseline, Week 6]

   IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

5. Mean Change From Baseline in IOP at 09:00 at Week 6 [Baseline, Week 6]

   IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 09:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

6. Mean Percentage Change From Baseline at 09:00 at Week 6 [Baseline, Week 6]

   IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 9:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits.A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of either open-angle glaucoma or ocular hypertension;

• Must sign an informed consent form;

• Mean IOP measurements at both the Eligibility 1 and 2 visits, in at least 1 eye (the same eye[s]) ≥ 19 and < 32 mmHg at 09:00.

• Willing and able to attend all study visits;

• Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

• Women of childbearing potential who are pregnant, breast-feeding, intend to become pregnant during the study, or not using adequate birth control methods to prevent pregnancy throughout the study;

• Any form of glaucoma other than open-angle glaucoma or ocular hypertension;

• Ocular disease, trauma, infection, inflammation, pathology, or surgery as specified in the protocol;

• Any other conditions including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study;

• Other protocol-specified exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Contact Alcon Call Center for Trial Locations	Fort Worth	Texas	United States	76134

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Clinical Manager, Ophtha, GCRA, Alcon, a Novartis Company

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 12, 2018
• Study Protocol - Mar 30, 2017

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT02419508
• Other Study ID Numbers: GLH694-P001; 2015-000736-15; REec-2015-1723
• First Posted: Apr 17, 2015
• Last Update Posted: Nov 15, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Glaucoma, Open-Angle; Ocular Hypertension; Brimonidine Tartrate; Bimatoprost; Travoprost; Pharmaceutical Solutions; Latanoprost; Ophthalmic Solutions; Brinzolamide

Study Results

Participant Flow

Recruitment Details	This study was conducted at 37 sites located in Argentina (3), Australia (4), Canada (12), Chile (3), France (1), Germany (3), Greece (2), Israel (3), Spain (3), and United Kingdom (3).
Pre-assignment Detail	Of the 290 subjects enrolled in the study, 102 were exited during the Screening/Eligibility period. This reporting group includes all randomized subjects. One randomized subject did not receive investigational product and is excluded from the Full Analysis Set and the Safety Analysis Set.

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Period Title: Overall Study
STARTED	96	92
Full Analysis Set	95	92
Safety Analysis Set	95	92
COMPLETED	86	88
NOT COMPLETED	10	4

Baseline Characteristics

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA	Total
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Total of all reporting groups
Overall Participants	95	92	187
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.5 (10.70)	67.9 (11.65)	67.2 (11.17)
Sex: Female, Male (Count of Participants)
Female	55 57.9%	43 46.7%	98 52.4%
Male	40 42.1%	49 53.3%	89 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 24.2%	29 31.5%	52 27.8%
Not Hispanic or Latino	72 75.8%	62 67.4%	134 71.7%
Unknown or Not Reported	0 0%	1 1.1%	1 0.5%
Baseline Diurnal IOP (millimeters mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeters mercury (mmHg)]	22.8 (2.39)	22.9 (2.32)	22.8 (2.35)
Region of Enrollment (Count of Participants)
Europe, Australia	45 47.4%	44 47.8%	89 47.6%
Latin America, Canada	50 52.6%	48 52.2%	98 52.4%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6
Description	IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Measure Participants	86	88
Mean (Standard Deviation) [mmHg]	-5.6 (2.72)	-2.1 (2.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIMBRINZA + PGA, Vehicle + PGA
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Mean Diurnal IOP at Week 6
Description	IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

FAS with data available

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Measure Participants	86	88
Mean (Standard Deviation) [mmHg]	17.2 (3.49)	20.9 (3.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIMBRINZA + PGA, Vehicle + PGA
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Mean Percentage Change From Baseline in Diurnal IOP at Week 6
Description	IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Measure Participants	86	88
Mean (Standard Deviation) [percent change]	-24.7 (12.17)	-9.5 (10.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIMBRINZA + PGA, Vehicle + PGA
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Mean Change From Baseline in IOP at 11:00 at Week 6
Description	IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Measure Participants	95	92
Baseline	22.4 (2.70)	22.6 (2.69)
Change from baseline	-7.0 (3.19)	-2.4 (2.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIMBRINZA + PGA, Vehicle + PGA
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

5. Secondary Outcome

Title	Mean Percentage Change From Baseline in IOP at 11:00 at Week 6
Description	IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Measure Participants	86	88
Mean (Standard Deviation) [percent change]	-31.3 (14.81)	-10.8 (11.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIMBRINZA + PGA, Vehicle + PGA
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Mean Change From Baseline in IOP at 09:00 at Week 6
Description	IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 09:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Measure Participants	95	92
Baseline	23.4 (2.40)	23.4 (2.22)
Change from baseline	-4.9 (3.06)	-2.5 (2.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIMBRINZA + PGA, Vehicle + PGA
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

7. Secondary Outcome

Title	Mean Percentage Change From Baseline at 09:00 at Week 6
Description	IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 9:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits.A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

Arm/Group Title	SIMBRINZA + PGA	Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days	Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Measure Participants	86	88
Mean (Standard Deviation) [percent change]	-21.0 (13.36)	-10.9 (11.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIMBRINZA + PGA, Vehicle + PGA
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Baseline through study completion, an average of 6 weeks.
Adverse Event Reporting Description	Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.This analysis population includes all subjects who received a dose of study medication (Safety Analysis Set).
Arm/Group Title	SIMBRINZA + PGA		Vehicle + PGA
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days		Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
All Cause Mortality
	SIMBRINZA + PGA		Vehicle + PGA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/95 (0%)		0/92 (0%)
Serious Adverse Events
	SIMBRINZA + PGA		Vehicle + PGA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/95 (1.1%)		0/92 (0%)
Cardiac disorders
Cardiac failure	1/95 (1.1%)	1	0/92 (0%)	0
Other (Not Including Serious) Adverse Events
	SIMBRINZA + PGA		Vehicle + PGA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/95 (10.5%)		1/92 (1.1%)
Eye disorders
Ocular hyperaemia	5/95 (5.3%)	9	1/92 (1.1%)	1
Gastrointestinal disorders
Dry mouth	5/95 (5.3%)	5	0/92 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.