Trial Outcomes & Findings for Safety and Efficacy of Triple Combination Therapy in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension (NCT NCT01217606)

Last Updated: 2016-12-20

Results Overview

Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) Hour 0 IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed using a two-sample t-test.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

185 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2016-12-20

Participant Flow

Patients were randomized into a 12-week Initial Treatment phase. Following this phase, patients may have continued into the 9-month Masked Extension on the same treatment assignment.

Participant milestones

Participant milestones
Measure	Triple Combination Therapy Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for 12 weeks in the Initial Treatment Phase followed by a 9 month Masked Extension.	Combigan® Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for 12 weeks in the Initial Treatment Phase followed by a 9 month Masked Extension.
Initial Treatment Phase STARTED	90	95
Initial Treatment Phase COMPLETED	76	83
Initial Treatment Phase NOT COMPLETED	14	12
9-Month Masked Extension STARTED	67	73
9-Month Masked Extension Not Enrolled in Masked Extension	9	10
9-Month Masked Extension COMPLETED	54	62
9-Month Masked Extension NOT COMPLETED	13	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Triple Combination Therapy Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for 12 weeks in the Initial Treatment Phase followed by a 9 month Masked Extension.	Combigan® Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for 12 weeks in the Initial Treatment Phase followed by a 9 month Masked Extension.
Initial Treatment Phase Other Reasons	0	2
Initial Treatment Phase Protocol Violation	3	2
Initial Treatment Phase Personal Reasons	0	2
Initial Treatment Phase Lack of Efficacy	1	0
Initial Treatment Phase Adverse Event	10	6
9-Month Masked Extension Adverse Event	3	6
9-Month Masked Extension Other Reasons	4	4
9-Month Masked Extension Personal Reasons	2	1
9-Month Masked Extension Lost to Follow-up	1	0
9-Month Masked Extension Pregnancy	1	0
9-Month Masked Extension Lack of Efficacy	2	0

Baseline Characteristics

Safety and Efficacy of Triple Combination Therapy in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Triple Combination Therapy n=90 Participants Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months.	Combigan® n=95 Participants Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months.	Total n=185 Participants Total of all reporting groups
Age, Customized ≤65 years	68 Participants n=93 Participants	62 Participants n=4 Participants	130 Participants n=27 Participants
Age, Customized >65 years	22 Participants n=93 Participants	33 Participants n=4 Participants	55 Participants n=27 Participants
Gender Female	53 Participants n=93 Participants	63 Participants n=4 Participants	116 Participants n=27 Participants
Gender Male	37 Participants n=93 Participants	32 Participants n=4 Participants	69 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Modified Intent to Treat: all randomized patients with at least one post-baseline efficacy evaluation

Outcome measures

Outcome measures
Measure	Triple Combination Therapy n=90 Participants Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months.	Combigan® n=95 Participants Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months.
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test Baseline	25.42 Millimeters of Mercury (mmHg) Standard Deviation 2.902	24.43 Millimeters of Mercury (mmHg) Standard Deviation 2.592
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test Change from Baseline at Week 12 (N=85, 93)	-10.45 Millimeters of Mercury (mmHg) Standard Deviation 3.175	-8.28 Millimeters of Mercury (mmHg) Standard Deviation 3.256

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Month 6, Month 9, Month 12

Population: Modified Intent to Treat: all randomized patients with at least one post-baseline efficacy evaluation and who have data at the noted time point (no missing imputation)

Outcome measures

Outcome measures
Measure	Triple Combination Therapy n=90 Participants Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months.	Combigan® n=95 Participants Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months.
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Baseline	25.42 Millimeters of Mercury (mmHg) Standard Deviation 2.902	24.43 Millimeters of Mercury (mmHg) Standard Deviation 2.592
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Week 2 (N=82, 87)	-11.24 Millimeters of Mercury (mmHg) Standard Deviation 3.283	-8.12 Millimeters of Mercury (mmHg) Standard Deviation 2.942
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Week 4 (N=82, 88)	-10.88 Millimeters of Mercury (mmHg) Standard Deviation 3.193	-8.35 Millimeters of Mercury (mmHg) Standard Deviation 3.100
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Week 8 (N=75, 87)	-10.53 Millimeters of Mercury (mmHg) Standard Deviation 3.165	-7.94 Millimeters of Mercury (mmHg) Standard Deviation 3.453
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Week 1 (N=82, 91)	-11.63 Millimeters of Mercury (mmHg) Standard Deviation 3.060	-8.13 Millimeters of Mercury (mmHg) Standard Deviation 2.969
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Week 12 (N=76, 83)	-10.56 Millimeters of Mercury (mmHg) Standard Deviation 3.224	-8.16 Millimeters of Mercury (mmHg) Standard Deviation 3.161
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Month 6 (N=64, 69)	-10.41 Millimeters of Mercury (mmHg) Standard Deviation 2.976	-8.29 Millimeters of Mercury (mmHg) Standard Deviation 3.221
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Month 9 (N=58, 67)	-10.29 Millimeters of Mercury (mmHg) Standard Deviation 3.275	-8.14 Millimeters of Mercury (mmHg) Standard Deviation 2.937
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure Change from Baseline at Month 12 (N=55, 63)	-9.38 Millimeters of Mercury (mmHg) Standard Deviation 3.398	-7.58 Millimeters of Mercury (mmHg) Standard Deviation 3.486

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Month 6, Month 9, Month 12

Population: Modified Intent to Treat: all randomized patients with at least one post-baseline efficacy evaluation

Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed by ANCOVA.

Outcome measures

Outcome measures
Measure	Triple Combination Therapy n=90 Participants Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months.	Combigan® n=95 Participants Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months.
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Baseline	25.42 Millimeters of Mercury (mmHg) Standard Deviation 2.902	24.43 Millimeters of Mercury (mmHg) Standard Deviation 2.592
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Week 1 (N=82, 91)	-11.63 Millimeters of Mercury (mmHg) Standard Deviation 3.060	-8.13 Millimeters of Mercury (mmHg) Standard Deviation 2.969
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Week 2 (N=84, 92)	-11.20 Millimeters of Mercury (mmHg) Standard Deviation 3.290	-8.28 Millimeters of Mercury (mmHg) Standard Deviation 3.076
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Week 4 (N=85, 93)	-10.85 Millimeters of Mercury (mmHg) Standard Deviation 3.180	-8.53 Millimeters of Mercury (mmHg) Standard Deviation 3.228
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Week 8 (N=85, 93)	-10.44 Millimeters of Mercury (mmHg) Standard Deviation 3.105	-8.07 Millimeters of Mercury (mmHg) Standard Deviation 3.521
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Week 12 (N=85, 93)	-10.45 Millimeters of Mercury (mmHg) Standard Deviation 3.175	-8.28 Millimeters of Mercury (mmHg) Standard Deviation 3.256
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Month 6 (N=67, 73)	-10.32 Millimeters of Mercury (mmHg) Standard Deviation 2.965	-8.42 Millimeters of Mercury (mmHg) Standard Deviation 3.252
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Month 9 (N=67, 73)	-10.09 Millimeters of Mercury (mmHg) Standard Deviation 3.349	-8.17 Millimeters of Mercury (mmHg) Standard Deviation 3.031
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) Change from Baseline at Month 12 (N=67, 73)	-9.36 Millimeters of Mercury (mmHg) Standard Deviation 3.368	-7.77 Millimeters of Mercury (mmHg) Standard Deviation 3.489

Adverse Events

Triple Combination Therapy

Serious events: 1 serious events

Other events: 84 other events

Deaths: 0 deaths

Combigan®

Serious events: 1 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Triple Combination Therapy n=90 participants at risk Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months.	Combigan® n=95 participants at risk Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	1.1% 1/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Musculoskeletal and connective tissue disorders Rotator Cuff Syndrome	1.1% 1/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	0.00% 0/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.

Other adverse events

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Triple Combination Therapy n=90 participants at risk Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months.	Combigan® n=95 participants at risk Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months.
Eye disorders Conjunctival hyperaemia	60.0% 54/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	29.5% 28/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Punctate keratitis	27.8% 25/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	20.0% 19/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Eye pruritus	13.3% 12/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	7.4% 7/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Blepharitis	16.7% 15/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	12.6% 12/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Erythema of eyelid	10.0% 9/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	7.4% 7/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Eye irritation	12.2% 11/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	3.2% 3/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Conjunctival follicles	7.8% 7/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	15.8% 15/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Meibomianitis	11.1% 10/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	8.4% 8/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Eye allergy	6.7% 6/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	5.3% 5/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Cataract	8.9% 8/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	3.2% 3/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Nervous system disorders Visual Field Defect	7.8% 7/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	7.4% 7/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Blepharal Pigmentation	6.7% 6/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	1.1% 1/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Skin and subcutaneous tissue disorders Hypertrichosis	5.6% 5/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	2.1% 2/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Infections and infestations Influenza	5.6% 5/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	2.1% 2/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Visual Acuity Reduced	5.6% 5/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	1.1% 1/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.
Eye disorders Pinguecula	4.4% 4/90 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.	6.3% 6/95 Advers events (AEs) and serious adverse events (SAEs) are reported for the Safety Population. The Safety Population included all treated patients who received at least 1 dose of the study medication and attended at least 1 post-baseline visit.