Safety and Efficacy of AGN-210669 Ophthalmic Solution Compared With Bimatoprost Ophthalmic Solution in Patients With Open-Angle Glaucoma or Ocular Hypertension

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01291108
• Collaborator: (none)
• Enrollment: 125
• Location: 1
• Arms: 6
• Duration (Months): 6
• Patients Per Site Per Month: 20.8

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of AGN-210669 ophthalmic solution compared with bimatoprost ophthalmic solution (Lumigan®) as monotherapy and adjunctive therapy in patients with primary open-angle glaucoma or ocular hypertension.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma, Open-Angle; Ocular Hypertension	Drug: AGN-210669; Drug: bimatoprost; Drug: bimatoprost vehicle	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AGN-210669 AGN-210669 0.05% applied as 1 drop in both eyes every evening during Month 1.	Drug: AGN-210669; AGN-210669 0.05% applied as 1 drop in both eyes every evening during Month 1 or Month 2.
Experimental: AGN-210669 + bimatoprost AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% applied as 1 drop of each treatment in both eyes every evening during Month 2.	Drug: AGN-210669; AGN-210669 0.05% applied as 1 drop in both eyes every evening during Month 1 or Month 2.; Drug: bimatoprost; bimatoprost ophthalmic solution 0.03% applied as 1 drop in both eyes every evening during Month 1 or Month 2.; Other Names: LUMIGAN®
Experimental: AGN-210669 + bimatoprost vehicle AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.	Drug: AGN-210669; AGN-210669 0.05% applied as 1 drop in both eyes every evening during Month 1 or Month 2.; Drug: bimatoprost vehicle; bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop in both eyes every evening during Month 2.
Active Comparator: bimatoprost bimatoprost ophthalmic solution 0.03% applied as 1 drop in both eyes every evening during Month 1.	Drug: bimatoprost; bimatoprost ophthalmic solution 0.03% applied as 1 drop in both eyes every evening during Month 1 or Month 2.; Other Names: LUMIGAN®
Experimental: bimatoprost + AGN-210669 bimatoprost ophthalmic solution 0.03% + AGN-210669 0.05% applied as 1 drop of each treatment in both eyes every evening during Month 2.	Drug: AGN-210669; AGN-210669 0.05% applied as 1 drop in both eyes every evening during Month 1 or Month 2.; Drug: bimatoprost; bimatoprost ophthalmic solution 0.03% applied as 1 drop in both eyes every evening during Month 1 or Month 2.; Other Names: LUMIGAN®
Other: bimatoprost + bimatoprost vehicle bimatoprost ophthalmic solution 0.03% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.	Drug: bimatoprost; bimatoprost ophthalmic solution 0.03% applied as 1 drop in both eyes every evening during Month 1 or Month 2.; Other Names: LUMIGAN® ; Drug: bimatoprost vehicle; bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop in both eyes every evening during Month 2.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Average Eye IOP [Baseline, Day 57]

   IOP is a measurement of the fluid pressure inside the eye. The average of the 2 eyes are used for the analyses. 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 recorded at Hours 0, 4, 8, and 12.

Secondary Outcome Measures

1. Change From Baseline in Worse Eye IOP [Baseline, Day 57]

   IOP is a measurement of the fluid pressure inside the eye. The worse eye IOP refers to eye with the worse baseline IOP, which is determined as the eye with the higher mean diurnal IOP at baseline. If both eyes have the same mean diurnal IOP at baseline, the right eye is designated as 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 recorded at Hours 0, 4, 8, and 12.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of primary open-angle glaucoma or ocular hypertension in each eye

• Requires bilateral treatment with an IOP-lowering medication

• Best corrected visual acuity of 20/100 or better in each eye

Exclusion Criteria:

• Use of oral, intramuscular, intravenous or topical ophthalmic corticosteroids within 2 months

• Inability to fast for up to 10 hours

• Prior refractive laser surgery (eg, LASIK, radial keratectomy, photorefractive keratectomy)

• Intraocular surgery or IOP-lowering laser surgery (eg, laser trabeculoplasty) within 6 months

• Current or anticipated use of artificial tears or any ocular medications aside from study medications during study

• Anticipated wearing of contact lenses during study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Austin	Texas	United States

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01291108
• Other Study ID Numbers: 210669-013
• First Posted: Feb 8, 2011
• Last Update Posted: Nov 6, 2013
• Last Verified: Nov 1, 2013

• Additional relevant MeSH terms: Glaucoma; Ocular Hypertension; Glaucoma, Open-Angle; Hypertension; Bimatoprost

Study Results

Participant Flow

Pre-assignment Detail	Pts were randomized at Baseline for the entire study. At Mo 1, pts received either AGN-210669 or bimatoprost. At Mo 2, pts who had received AGN-210669, then received either AGN-210669+bimatoprost or AGN-210669+bimatoprost vehicle and pts who had received bimatoprost, then received either bimatoprost+AGN-210669 or bimatoprost+bimatoprost vehicle.

Arm/Group Title	AGN-210669	AGN-210669 + Bimatoprost	AGN-210669 + Bimatoprost Vehicle	Bimatoprost	Bimatoprost + AGN-210669	Bimatoprost + Bimatoprost Vehicle
Arm/Group Description	AGN-210669 0.05% applied as 1 drop in both eyes every evening during Month 1.	AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% applied as 1 drop of each treatment in both eyes every evening during Month 2.	AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.	bimatoprost ophthalmic solution 0.03% applied as 1 drop in both eyes every evening during Month 1.	bimatoprost ophthalmic solution 0.03% + AGN-210669 0.05% applied as 1 drop of each treatment in both eyes every evening during Month 2.	bimatoprost ophthalmic solution 0.03% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.
Period Title: Month 1 (Monotherapy)
STARTED	65	0	0	60	0	0
COMPLETED	64	0	0	60	0	0
NOT COMPLETED	1	0	0	0	0	0
Period Title: Month 1 (Monotherapy)
STARTED	0	40	24	0	34	26
COMPLETED	0	38	24	0	34	25
NOT COMPLETED	0	2	0	0	0	1

Baseline Characteristics

Arm/Group Title	AGN-210669 Followed by AGN-210669 + Bimatoprost	AGN-210669 Followed by AGN-210669 + Bimatoprost Vehicle	Bimatoprost Followed by Bimatoprost + AGN-210669	Bimatoprost Followed by Bimatoprost + Bimatoprost Vehicle	Total
Arm/Group Description	AGN-210669 0.05% applied as 1 drop in each eye every evening for Month 1 followed by AGN-210669 0.05% + bimatoprost 0.03% applied as 1 drop of each treatment in both eyes every evening for Month 2.	AGN-210669 0.05% applied as 1 drop in each eye every evening for Month 1 followed by AGN-210669 0.05% + bimatoprost 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening for Month 2.	bimatoprost 0.03% applied as 1 drop in each eye every evening for Month 1 followed by bimatoprost 0.03% + AGN-210669 applied as 1 drop of each treatment in both eyes every evening for Month 2.	bimatoprost 0.03% applied as 1 drop in each eye every evening for Month 1 followed by bimatoprost 0.03% + bimatoprost 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening for Month 2.	Total of all reporting groups
Overall Participants	44	21	40	20	125
Age, Customized (Number) [Number]
<45 years	1 2.3%	1 4.8%	1 2.5%	0 0%	3 2.4%
45 to 65 years	17 38.6%	10 47.6%	20 50%	7 35%	54 43.2%
>65 years	26 59.1%	10 47.6%	19 47.5%	13 65%	68 54.4%
Sex: Female, Male (Count of Participants)
Female	27 61.4%	15 71.4%	27 67.5%	13 65%	82 65.6%
Male	17 38.6%	6 28.6%	13 32.5%	7 35%	43 34.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Average Eye IOP
Description	IOP is a measurement of the fluid pressure inside the eye. The average of the 2 eyes are used for the analyses. 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 recorded at Hours 0, 4, 8, and 12.
Time Frame	Baseline, Day 57

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat: all randomized and treated patients who had a baseline and at least 1 post-baseline IOP measurement

Arm/Group Title	AGN-210669 Followed by AGN-210669 + Bimatoprost Vehicle	Bimatoprost Followed by Bimatoprost + Bimatoprost Vehicle	Combined Adjunctives
Arm/Group Description	AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.	bimatoprost ophthalmic solution 0.03% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.	Combined adjunctives refer to the combined groups of 'AGN-210669 0.05% + bimatoprost' and 'bimatoprost + AGN-210669 0.05%'. The first treatment is applied as 1 drop in each eye every evening for Month 1 followed by AGN-210669 0.05% + bimatoprost 0.03% applied as 1 drop of each treatment in both eyes every evening for Month 2.
Measure Participants	24	26	75
Baseline - Hour 0	26.16 (2.169)	25.98 (1.962)	26.26 (2.446)
Baseline - Hour 4	23.91 (2.382)	23.82 (2.301)	23.85 (2.553)
Baseline - Hour 8	22.49 (1.338)	22.35 (2.024)	22.79 (2.391)
Baseline - Hour 12	21.48 (2.467)	22.07 (2.596)	21.73 (2.624)
Change from Baseline at Day 57-Hr 0 (n=24,25,72)	-7.57 (2.881)	-10.28 (3.190)	-10.84 (3.460)
Change from Baseline at Day 57-Hr 4 (n=24,25,72)	-6.95 (2.503)	-8.95 (3.531)	-8.79 (3.330)
Change from Baseline at Day 57-Hr 8 (n=24,25,72)	-5.57 (3.484)	-7.19 (3.198)	-7.67 (2.596)
Change from Baseline at Day 57-Hr 12 (n=16,17,56)	-5.31 (2.690)	-6.87 (2.838)	-6.03 (2.642)

2. Secondary Outcome

Title	Change From Baseline in Worse Eye IOP
Description	IOP is a measurement of the fluid pressure inside the eye. The worse eye IOP refers to eye with the worse baseline IOP, which is determined as the eye with the higher mean diurnal IOP at baseline. If both eyes have the same mean diurnal IOP at baseline, the right eye is designated as 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 recorded at Hours 0, 4, 8, and 12.
Time Frame	Baseline, Day 57

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat: all randomized and treated patients who had a baseline and at least 1 post-baseline IOP measurement

Arm/Group Title	AGN-210669 Followed by AGN-210669 + Bimatoprost Vehicle	Bimatoprost Followed by Bimatoprost + Bimatoprost Vehicle	Combined Adjunctives
Arm/Group Description	AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.	bimatoprost ophthalmic solution 0.03% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.	Combined adjunctives refer to the combined groups of 'AGN-210669 0.05% + bimatoprost' and 'bimatoprost + AGN-210669 0.05%'. The first treatment is applied as 1 drop in each eye every evening for Month 1 followed by AGN-210669 0.05% + bimatoprost 0.03% applied as 1 drop of each treatment in both eyes every evening for Month 2.
Measure Participants	24	26	75
Baseline - Hour 0	26.56 (2.305)	26.40 (2.069)	26.61 (2.664)
Baseline - Hour 4	24.60 (2.754)	24.25 (2.295)	24.31 (2.685)
Baseline - Hour 8	23.04 (1.687)	22.73 (2.290)	23.17 (2.591)
Baseline - Hour 12	21.72 (2.811)	22.47 (2.598)	21.93 (2.908)
Change from Baseline at Day 57-Hr 0 (n=24,25,72)	-7.50 (2.989)	-10.56 (3.435)	-10.96 (3.705)
Change from Baseline at Day 57-Hr 4 (n=24,25,72)	-7.38 (2.841)	-9.16 (3.472)	-9.01 (3.515)
Change from Baseline at Day 57-Hr 8 (n=24,25,72)	-5.94 (3.817)	-7.42 (3.526)	-7.92 (3.002)
Change from Baseline at Day 57-Hr 12 (n=16,17,56)	-5.00 (2.696)	-7.00 (2.969)	-5.99 (3.076)

Adverse Events

Adverse Event Reporting Description	The Safety Population was used to assess adverse events (AEs) and serious adverse events (SAEs) and included all treated patients. SAEs and AEs are presented by treatment arm not necessarily by individual treatment received.
Arm/Group Title	AGN-210669		AGN-210669 + Bimatoprost		AGN-210669 + Bimatoprost Vehicle		Bimatoprost		Bimatoprost + AGN-210669		Bimatoprost + Bimatoprost Vehicle
Arm/Group Description	AGN-210669 0.05% applied as 1 drop in both eyes every evening during Month 1.		AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% applied as 1 drop of each treatment in both eyes every evening during Month 2.		AGN-210669 0.05% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.		bimatoprost ophthalmic solution 0.03% applied as 1 drop in both eyes every evening during Month 1.		bimatoprost ophthalmic solution 0.03% + AGN-210669 0.05% applied as 1 drop of each treatment in both eyes every evening during Month 2.		bimatoprost ophthalmic solution 0.03% + bimatoprost ophthalmic solution 0.03% vehicle applied as 1 drop of each treatment in both eyes every evening during Month 2.
All Cause Mortality
	AGN-210669		AGN-210669 + Bimatoprost		AGN-210669 + Bimatoprost Vehicle		Bimatoprost		Bimatoprost + AGN-210669		Bimatoprost + Bimatoprost Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AGN-210669		AGN-210669 + Bimatoprost		AGN-210669 + Bimatoprost Vehicle		Bimatoprost		Bimatoprost + AGN-210669		Bimatoprost + Bimatoprost Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/40 (0%)		0/24 (0%)		0/60 (0%)		0/34 (0%)		1/26 (3.8%)
Injury, poisoning and procedural complications
Uveal Prolapse	0/65 (0%)		0/40 (0%)		0/24 (0%)		0/60 (0%)		0/34 (0%)		1/26 (3.8%)
Other (Not Including Serious) Adverse Events
	AGN-210669		AGN-210669 + Bimatoprost		AGN-210669 + Bimatoprost Vehicle		Bimatoprost		Bimatoprost + AGN-210669		Bimatoprost + Bimatoprost Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/65 (66.2%)		31/40 (77.5%)		11/24 (45.8%)		41/60 (68.3%)		26/34 (76.5%)		15/26 (57.7%)
Eye disorders
Corneal Thickening	19/65 (29.2%)		10/40 (25%)		4/24 (16.7%)		2/60 (3.3%)		15/34 (44.1%)		0/26 (0%)
Conjunctival Hyperaemia	17/65 (26.2%)		23/40 (57.5%)		2/24 (8.3%)		24/60 (40%)		13/34 (38.2%)		5/26 (19.2%)
Eye Irritation	6/65 (9.2%)		4/40 (10%)		1/24 (4.2%)		2/60 (3.3%)		3/34 (8.8%)		1/26 (3.8%)
Eye Discharge	5/65 (7.7%)		3/40 (7.5%)		0/24 (0%)		3/60 (5%)		1/34 (2.9%)		1/26 (3.8%)
Vision Blurred	5/65 (7.7%)		5/40 (12.5%)		0/24 (0%)		3/60 (5%)		5/34 (14.7%)		0/26 (0%)
Eye Pruritus	4/65 (6.2%)		3/40 (7.5%)		0/24 (0%)		4/60 (6.7%)		5/34 (14.7%)		0/26 (0%)
Punctate Keratitis	3/65 (4.6%)		6/40 (15%)		3/24 (12.5%)		7/60 (11.7%)		4/34 (11.8%)		4/26 (15.4%)
Photophobia	3/65 (4.6%)		10/40 (25%)		0/24 (0%)		4/60 (6.7%)		12/34 (35.3%)		1/26 (3.8%)
Foreign Body Sensation in Eyes	2/65 (3.1%)		5/40 (12.5%)		0/24 (0%)		6/60 (10%)		3/34 (8.8%)		0/26 (0%)
Eye Pain	0/65 (0%)		9/40 (22.5%)		1/24 (4.2%)		0/60 (0%)		8/34 (23.5%)		2/26 (7.7%)
Lacrimation Increased	3/65 (4.6%)		2/40 (5%)		0/24 (0%)		0/60 (0%)		2/34 (5.9%)		0/26 (0%)
Iritis	0/65 (0%)		3/40 (7.5%)		0/24 (0%)		0/60 (0%)		0/34 (0%)		0/26 (0%)
Anterior Chamber Cell	0/65 (0%)		2/40 (5%)		0/24 (0%)		0/60 (0%)		1/34 (2.9%)		2/26 (7.7%)
Asthenopia	0/65 (0%)		2/40 (5%)		0/24 (0%)		0/60 (0%)		0/34 (0%)		0/26 (0%)
Keratitis	0/65 (0%)		2/40 (5%)		0/24 (0%)		0/60 (0%)		0/34 (0%)		0/26 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.