Additive Effect of Twice-daily Brinzolamide 1%/Brimonidine 0.2%Combination as an Adjunctive Therapy to Travoprost in Patients With Normal Tension Glaucoma

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03150160
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study was to determine the incremental intraocular pressure (IOP) lowering that is achieved when Simbrinza is used adjunctively to Travatan in patients with normal tension glaucoma that may benefit from further IOP lowering.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: brinzolamide 1%/brimonidine 0.2% fixed combination; Drug: Placebo; Drug: travoprost 0.004% ophthalmic solution	Phase 4

Detailed Description

This study was prematurely terminated due to administrative reasons and not due to any safety or efficacy concerns.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This was a multicenter, randomized, double-masked, two-arm, placebo-controlled, parallel group study in patients with normal tension glaucoma who were insufficiently controlled on travoprost 0.004% (Travatan) monotherapy.This was a multicenter, randomized, double-masked, two-arm, placebo-controlled, parallel group study in patients with normal tension glaucoma who were insufficiently controlled on travoprost 0.004% (Travatan) monotherapy.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 6-week, Double Masked, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Twice-daily Brinzolamide 1%/Brimonidine 0.2% Fixed Dose Combination as an Adjunctive Therapy to Travoprost 0.004% in Reducing Intraocular Pressure in Patients With Normal Tension Glaucoma
• Actual Study Start Date: Sep 21, 2017
• Actual Primary Completion Date: Dec 4, 2017
• Actual Study Completion Date: Dec 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Simbrinza + Travatan Brinzolamide 1%/brimonidine 0.2% fixed combination + travoprost 0.004% ophthalmic solution	Drug: brinzolamide 1%/brimonidine 0.2% fixed combination; One drop applied topically to the affected eye(s) in the morning and evening; Other Names: Simbrinza ; Drug: travoprost 0.004% ophthalmic solution; One drop applied topically to the affected eye(s) in the evening; Other Names: Travatan
Placebo Comparator: Placebo + Travatan Placebo + travoprost 0.004% ophthalmic solution	Drug: Placebo; One drop applied topically to the affected eye(s) in the morning and evening; Drug: travoprost 0.004% ophthalmic solution; One drop applied topically to the affected eye(s) in the evening; Other Names: Travatan

Outcome Measures

Primary Outcome Measures

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

   IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry in millimeters mercury (mmHg). Diurnal IOP was defined as the average of the 9:00 am and 11:00 am time points. A more negative change value indicates a greater amount of improvement. One eye (study eye) contributed to the analysis.

Secondary Outcome Measures

1. Percent Change From Baseline in IOP at Week 6 [Baseline, Week 6]

   IOP was measured by Goldmann applanation tonometry in mmHg. A more negative percent change value indicates a greater amount of improvement. One eye (study eye) contributed to the analysis.

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

   IOP was measured by Goldmann applanation tonometry in mmHg. Diurnal IOP was defined as the average of the 9:00 and 11:00 time points. One (study eye) contributed to the analysis.

3. Mean Change From Baseline in IOP for Each Time Point at Week 6 [Baseline (9:00 am and 11:00 am), Week 6 (9:00 am and 11:00 am)]

   IOP was measured by Goldmann applanation tonometry in mmHg. A more negative change value indicates a greater amount of improvement. One eye (study eye) contributed to the analysis.

4. Percentage Change From Baseline in IOP for Each Time Point at Week 6 [Baseline, Week 6]

   IOP was measured by Goldmann applanation tonometry in mmHg. A more negative percent change value indicates a greater amount of improvement. 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:

• Sign written informed consent

• Diagnosed with normal tension glaucoma

• Intraocular pressure measurements in at least 1 eye as specified in the protocol

• Willing and able to attend all study visits

Exclusion Criteria:

• History of hypersensitivity to any of the study drugs

• Use of medications prohibited by the protocol

• Pregnant or nursing

• Of child-bearing potential unless using contraception, as specified in the protocol

• Any form of glaucoma other than open angle glaucoma in either eye

• Chronic, recurrent or severe inflammatory eye disease

• Ocular trauma or surgery within the past 6 months in either eye; ocular infection or laser surgery within the past 3 months in either eye (all from screening)

• Conditions which would make the patient, in the opinion of the Investigator, unsuitable for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Seoul		Korea, Republic of	03080

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Apr 9, 2018
• Statistical Analysis Plan - Aug 28, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03150160
• Other Study ID Numbers: CQVJ499A2404
• First Posted: May 12, 2017
• Last Update Posted: Feb 25, 2019
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: travoprost; brinzolamide 1%/brimonidine 0.2%; normal tension glaucoma; intraocular pressure; efficacy; safety
• Additional relevant MeSH terms: Glaucoma; Low Tension Glaucoma; Brimonidine Tartrate; Travoprost; Ophthalmic Solutions; Brinzolamide

Study Results

Participant Flow

Pre-assignment Detail	All randomized patients (1). Note: No patients were randomized to the Simbrinza + Travatan arm.

Arm/Group Title	Simbrinza + Travatan	Placebo + Travatan
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination (morning and evening) + travoprost 0.004% ophthalmic solution (evening)	Placebo (morning and evening) + travoprost 0.004% ophthalmic solution (evening)
Period Title: Overall Study
STARTED	0	1
COMPLETED	0	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Simbrinza + Travatan	Placebo + Travatan	Total
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination (morning and evening) + travoprost 0.004% ophthalmic solution (evening)	Placebo (morning and evening) + travoprost 0.004% ophthalmic solution (evening)	Total of all reporting groups
Overall Participants	0	1	1
Age (Count of Participants)
<=18 years	0 NaN	0 0%	0 0%
Between 18 and 65 years	0 NaN	0 0%	0 0%
>=65 years	0 NaN	1 100%	1 100%
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 0%	0 0%
Male	0 NaN	1 100%	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 NaN	0 0%	0 0%
Not Hispanic or Latino	0 NaN	1 100%	1 100%
Unknown or Not Reported	0 NaN	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Diurnal IOP at Week 6
Description	IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry in millimeters mercury (mmHg). Diurnal IOP was defined as the average of the 9:00 am and 11:00 am time points. A more negative change value indicates a greater amount of improvement. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

At the time of the premature termination of this study, only 1 patient was randomized. Therefore, the planned efficacy and safety analyses could not be performed. No data to report.

Arm/Group Title	Simbrinza + Travatan	Placebo + Travatan
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination + travoprost 0.004% ophthalmic solution	Placebo + travoprost 0.004% ophthalmic solution
Measure Participants	0	0

2. Secondary Outcome

Title	Percent Change From Baseline in IOP at Week 6
Description	IOP was measured by Goldmann applanation tonometry in mmHg. A more negative percent change value indicates a greater amount of improvement. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

At the time of the premature termination of this study, only 1 patient was randomized. Therefore, the planned efficacy and safety analyses could not be performed. No data to report.

Arm/Group Title	Simbrinza + Travatan	Placebo + Travatan
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination + travoprost 0.004% ophthalmic solution	Placebo + travoprost 0.004% ophthalmic solution
Measure Participants	0	0

3. Secondary Outcome

Title	Mean Diurnal IOP at Week 6
Description	IOP was measured by Goldmann applanation tonometry in mmHg. Diurnal IOP was defined as the average of the 9:00 and 11:00 time points. One (study eye) contributed to the analysis.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

At the time of the premature termination of this study, only 1 patient was randomized. Therefore, the planned efficacy and safety analyses could not be performed. No data to report.

Arm/Group Title	Simbrinza + Travatan	Placebo + Travatan
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination + travoprost 0.004% ophthalmic solution	Placebo + travoprost 0.004% ophthalmic solution
Measure Participants	0	0

4. Secondary Outcome

Title	Mean Change From Baseline in IOP for Each Time Point at Week 6
Description	IOP was measured by Goldmann applanation tonometry in mmHg. A more negative change value indicates a greater amount of improvement. One eye (study eye) contributed to the analysis.
Time Frame	Baseline (9:00 am and 11:00 am), Week 6 (9:00 am and 11:00 am)

Outcome Measure Data

Analysis Population Description

At the time of the premature termination of this study, only 1 patient was randomized. Therefore, the planned efficacy and safety analyses could not be performed. No data to report.

Arm/Group Title	Simbrinza + Travatan	Placebo + Travatan
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination + travoprost 0.004% ophthalmic solution	Placebo + travoprost 0.004% ophthalmic solution
Measure Participants	0	0

5. Secondary Outcome

Title	Percentage Change From Baseline in IOP for Each Time Point at Week 6
Description	IOP was measured by Goldmann applanation tonometry in mmHg. A more negative percent change value indicates a greater amount of improvement. One eye (study eye) contributed to the analysis.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

At the time of the premature termination of this study, only 1 patient was randomized. Therefore, the planned efficacy and safety analyses could not be performed. No data to report.

Arm/Group Title	Simbrinza + Travatan	Placebo + Travatan
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination + travoprost 0.004% ophthalmic solution	Placebo + travoprost 0.004% ophthalmic solution
Measure Participants	0	0

Adverse Events

Time Frame	Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately six weeks.
Adverse Event Reporting Description	The Safety analysis set included all patients exposed to at least one dose of any study therapy. Note: Number at risk for Simbrinza + Travatan is reported as 0 because no patients were exposed to this study therapy.
Arm/Group Title	Simbrinza + Travatan		Placebo + Travatan
Arm/Group Description	Brinzolamide 1%/brimonidine 0.2% fixed combination (morning and evening) + travoprost 0.004% ophthalmic solution (evening)		Placebo (morning and evening) + travoprost 0.004% ophthalmic solution (evening)
All Cause Mortality
	Simbrinza + Travatan		Placebo + Travatan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)
Serious Adverse Events
	Simbrinza + Travatan		Placebo + Travatan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Simbrinza + Travatan		Placebo + Travatan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		1/1 (100%)
Infections and infestations
common cold	0/0 (NaN)		1/1 (100%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.