BEACON: A Safety and Efficacy Study of Brimonidine Intravitreal Implant in Geographic Atrophy Secondary to Age-related Macular Degeneration

• Sponsor: Allergan (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02087085
• Collaborator: (none)
• Enrollment: 310
• Locations: 41
• Arms: 2
• Actual Duration (Months): 46.7
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will assess the safety and efficacy of the brimonidine intravitreal implant in participants with geographic atrophy due to age-related macular degeneration.

Condition or Disease	Intervention/Treatment	Phase
Geographic Atrophy; Macular Degeneration	Drug: 400 µg Brimonidine Implant; Other: Sham	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Brimonidine Posterior Segment Drug Delivery System in Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration
• Actual Study Start Date: May 9, 2014
• Actual Primary Completion Date: Mar 30, 2018
• Actual Study Completion Date: Mar 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 400 µg Brimonidine Implant 400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21.	Drug: 400 µg Brimonidine Implant; 400 µg brimonidine implant in the study eye using Brimo DDS® applicator on Day 1, and every 3 months through Month 21.; Other Names: AGN-190342
Sham Comparator: Sham Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless drug delivery system (DDS) applicator every 3 months from Baseline (Day 1) through Month 21.	Other: Sham; Sham treatment with needleless applicator (no implant) to the study eye on Day 1, and every 3 months through Month 21.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Geographic Atrophy (GA) Lesion Area of the Study Eye as Assessed by Fundus Autofluorescence (FAF) at Month 24 [Baseline (Day 1) to Month 24]

   GA lesion area was measured in mm^2 by FAF in the study eye and was quantified by the central reading center. The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard Best Correct Visual Acuity (BCVA). If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression). Mixed model for repeated measures (MMRM) was used for analysis.

Secondary Outcome Measures

1. Change From Baseline in Standard Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Month 24 [Baseline (Day 1) to Month 24]

   BCVA was measured using an eye chart (ETDRS) and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis.

2. Change From Baseline in Low Luminance BCVA Score as Assessed by ETDRS Chart at Month 24 [Baseline (Day 1) to Month 24]

   Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis.

Other Outcome Measures

1. Change From Baseline in Retinal Sensitivity in the Study Eye [Baseline (Day 1) to Month 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Geographic atrophy due to age-related macular degeneration in the study eye

• Visual acuity better than or equal to 20/125 Snellen equivalent in the study eye and 20/200 Snellen equivalent in the fellow eye.

Exclusion Criteria:

• Cataract surgery or Laser-Assisted in situ Keratomileusis (LASIK) in the study eye in the last 3 months

• Infections in either eye in the last 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Consultants of Arizona, Ltd., Retinal Research Institute	Phoenix	Arizona	United States	85014
2	Associated Retina Consultants	Phoenix	Arizona	United States	85020
3	University of California, San Diego, Jacobs Retina Center, Shiley Eye Center	La Jolla	California	United States	92037
4	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
5	Retina Consultants of Southern Colorado, PC	Colorado Springs	Colorado	United States	80909
6	"National Ophthalmic Research Institute Retina Consultants of Southwest Florida"	Fort Myers	Florida	United States	33912
7	Retina Specialty Institute	Pensacola	Florida	United States	32503
8	Retina Vitreous Associates of Florida	Saint Petersburg	Florida	United States	33711
9	Southern Vitreoretinal Associates, PL	Tallahassee	Florida	United States	32308
10	Center for Retina and Macular Disease	Winter Haven	Florida	United States	33880
11	Georgia Retina	Decatur	Georgia	United States	30030
12	Raj K. Maturi, MD	Indianapolis	Indiana	United States	46290
13	Retina Associates of Western New York	Rochester	New York	United States	14620
14	Charlotte Eye Ear Nose & Throat Associates, PA	Charlotte	North Carolina	United States	28210
15	Oregon Retina, LLP	Eugene	Oregon	United States	97401
16	Casey Eye Institute, Oregon Health and Science University	Portland	Oregon	United States	97239
17	Mid Atlantic Retina, Wills Eye Retina Surgeons	Philadelphia	Pennsylvania	United States	19107
18	Retina Research Institute of Texas	Abilene	Texas	United States	79606
19	Texas Retina Associates	Arlington	Texas	United States	76012
20	"Austin Retina Associates "	Austin	Texas	United States	78705
21	Retina Foundation of the Southwest	Dallas	Texas	United States	75231
22	Valley Retina Institute	McAllen	Texas	United States	78503
23	Strategic Clinical Research Group, LLC	Willow Park	Texas	United States	76087
24	Center for Eye Research Australia	Melbourne	Victoria	Australia	3002
25	Lions Eye Institute, University of Western Australia	Nedlands		Australia	6009
26	Service d'Ophtalmologie	Bordeaux		France	33076
27	"Centre Hospitalier Intercommunal de Creteil "	Creteil		France	94000
28	"Universitat Bonn, Abteilung fur Augenheilkunde "	Bonn		Germany	53127
29	STZ Eyetrial	Tübingen		Germany	72076
30	Università di Cagliari (presidio San Giovanni di Dio)	Bologna		Italy	40138
31	Università di Cagliari (presidio San Giovanni di Dio)	Cagliari		Italy	09124
32	Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico	Milano		Italy	20122
33	IRCCS Ospedale San Raffaele	Milano		Italy	20132
34	"Dir IV Clinica Oculistica di Milano, Ospedale Generale ""Luigi Sacco"" "	Milano		Italy	20157
35	Universita degli Studi di Padova, Dipartimento di Neuroscienze	Padova		Italy	35128
36	Universita degli Studi di Torino	Torino		Italy	10122
37	Clinical Research Unit, Level2, Bristol Eye Hospital, Lower Maudlin Street	Bristol		United Kingdom	BS1 2LX
38	Frimley Park Hospital, Eye clinical trials Unit, Department of Opthalmology	Camberley		United Kingdom	GU16 7UJ
39	Moorfields Eye Hospital	London		United Kingdom	EC1V 2PD
40	Macular Unit, Hospital of St Cross	Rugby		United Kingdom	CV22 5PX
41	Royal Hallamshire Hospital, Eye Department	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Claire Winterson, Allergan

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 3, 2018
• Study Protocol - May 23, 2017

More Information

Additional Information:

• More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02087085
• Other Study ID Numbers: 190342-038; 2013-003320-36
• First Posted: Mar 14, 2014
• Last Update Posted: Apr 23, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Macular Degeneration; Geographic Atrophy; Atrophy; Brimonidine Tartrate

Study Results

Participant Flow

Arm/Group Title	400 µg Brimonidine Implant	Sham
Arm/Group Description	400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21.	Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless drug delivery system (DDS) applicator every 3 months from Baseline (Day 1) through Month 21.
Period Title: Overall Study
STARTED	154	156
COMPLETED	34	40
NOT COMPLETED	120	116

Baseline Characteristics

Arm/Group Title	400 µg Brimonidine Implant	Sham	Total
Arm/Group Description	400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21.	Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless DDS applicator every 3 months from Baseline (Day 1) through Month 21.	Total of all reporting groups
Overall Participants	154	156	310
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.9 (7.89)	77.0 (7.24)	76.9 (7.56)
Sex: Female, Male (Count of Participants)
Female	101 65.6%	91 58.3%	192 61.9%
Male	53 34.4%	65 41.7%	118 38.1%
Race/Ethnicity, Customized (Count of Participants)
White	153 99.4%	156 100%	309 99.7%
Black or African American	1 0.6%	0 0%	1 0.3%
Geographic Atrophy (GA) Lesion Area by Fundus Autofluorescence (FAF) (millimeters squared (mm^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeters squared (mm^2)]	5.1611 (3.7016)	5.4761 (3.5961)	5.3212 (3.6457)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Geographic Atrophy (GA) Lesion Area of the Study Eye as Assessed by Fundus Autofluorescence (FAF) at Month 24
Description	GA lesion area was measured in mm^2 by FAF in the study eye and was quantified by the central reading center. The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard Best Correct Visual Acuity (BCVA). If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression). Mixed model for repeated measures (MMRM) was used for analysis.
Time Frame	Baseline (Day 1) to Month 24

Outcome Measure Data

Analysis Population Description

Participants from the mITT population, all randomized and treated participants with baseline and at least 1 postbaseline assessment for GA lesion area by FAF, with data available for analysis at Month 24.

Arm/Group Title	400 µg Brimonidine Implant	Sham
Arm/Group Description	400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21.	Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless DDS applicator every 3 months from Baseline (Day 1) through Month 21.
Measure Participants	86	90
Least Squares Mean (Standard Error) [mm^2]	3.1455 (0.1377)	3.5044 (0.1359)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 µg Brimonidine Implant, Sham
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments	MMRM model included treatment group, study region, analysis visit and treatment-by-visit interaction as factors and baseline value and baseline value-by-analysis visit interaction as covariates.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.3589
	Confidence Interval	(2-Sided) 95%; -0.7132 to -0.0047
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1804
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Standard Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Month 24
Description	BCVA was measured using an eye chart (ETDRS) and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis.
Time Frame	Baseline (Day 1) to Month 24

Outcome Measure Data

Analysis Population Description

Participants from the mITT population, all randomized and treated participants with baseline and at least 1 postbaseline assessment for GA lesion area by FAF, with data available for analysis for this outcome measure at Month 24.

Arm/Group Title	400 µg Brimonidine Implant	Sham
Arm/Group Description	400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21.	Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless DDS applicator every 3 months from Baseline (Day 1) through Month 21.
Measure Participants	81	82
Least Squares Mean (Standard Error) [letters read correctly]	-10.9 (1.0)	-9.7 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 µg Brimonidine Implant, Sham
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.390
	Comments	MMRM model included treatment group, study region, analysis visit and treatment-by-visit interaction as factors and baseline value and baseline value-by-analysis visit interaction as covariates.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -3.9 to 1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Low Luminance BCVA Score as Assessed by ETDRS Chart at Month 24
Description	Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis.
Time Frame	Baseline (Day 1) to Month 24

Outcome Measure Data

Analysis Population Description

Participants from the mITT population, all randomized and treated participants with baseline and at least 1 postbaseline assessment for GA lesion area by FAF, with data available for analysis for this outcome measure at Month 24.

Arm/Group Title	400 µg Brimonidine Implant	Sham
Arm/Group Description	400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21.	Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless DDS applicator every 3 months from Baseline (Day 1) through Month 21.
Measure Participants	81	82
Least Squares Mean (Standard Error) [letters read correctly]	-8.1 (1.0)	-6.7 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 µg Brimonidine Implant, Sham
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.301
	Comments	MMRM model included treatment group, study region, analysis visit and treatment-by-visit interaction as factors and baseline value and baseline value-by-analysis visit interaction as covariates.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -4.2 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

4. Other Pre-specified Outcome

Title	Change From Baseline in Retinal Sensitivity in the Study Eye
Time Frame	Baseline (Day 1) to Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From first dose of study drug to date of last visit (up to approximately 33 months)
Adverse Event Reporting Description	Safety population included all participants who received at least 1 administration of study treatment.
Arm/Group Title	400 µg Brimonidine Implant		Sham
Arm/Group Description	400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21.		Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless DDS applicator every 3 months from Baseline (Day 1) through Month 21.
All Cause Mortality
	400 µg Brimonidine Implant		Sham
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/154 (3.2%)		6/156 (3.8%)
Serious Adverse Events
	400 µg Brimonidine Implant		Sham
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/154 (31.2%)		37/156 (23.7%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/154 (0.6%)		0/156 (0%)
Cardiac disorders
Acute myocardial infarction	3/154 (1.9%)		0/156 (0%)
Atrial fibrillation	3/154 (1.9%)		1/156 (0.6%)
Bradycardia	3/154 (1.9%)		0/156 (0%)
Cardiac failure congestive	3/154 (1.9%)		1/156 (0.6%)
Coronary artery disease	2/154 (1.3%)		1/156 (0.6%)
Sinus node dysfunction	2/154 (1.3%)		0/156 (0%)
Atrioventricular block complete	1/154 (0.6%)		0/156 (0%)
Coronary artery stenosis	1/154 (0.6%)		0/156 (0%)
Myocardial infarction	1/154 (0.6%)		0/156 (0%)
Pericardial effusion	1/154 (0.6%)		0/156 (0%)
Angina pectoris	0/154 (0%)		1/156 (0.6%)
Cardiopulmonary failure	0/154 (0%)		1/156 (0.6%)
Endocrine disorders
Hypothyroidism	1/154 (0.6%)		0/156 (0%)
Eye disorders
Visual acuity reduced	2/154 (1.3%)		0/156 (0%)
Vitreous haemorrhage	2/154 (1.3%)		0/156 (0%)
Retinal tear	1/154 (0.6%)		0/156 (0%)
Retinal vein occlusion	1/154 (0.6%)		0/156 (0%)
Anterior capsule contraction	0/154 (0%)		1/156 (0.6%)
Cataract	0/154 (0%)		1/156 (0.6%)
Gastrointestinal disorders
Diarrhoea	1/154 (0.6%)		0/156 (0%)
Pancreatitis	1/154 (0.6%)		0/156 (0%)
Abdominal hernia	0/154 (0%)		1/156 (0.6%)
Gastrointestinal haemorrhage	0/154 (0%)		1/156 (0.6%)
Hiatus hernia	0/154 (0%)		1/156 (0.6%)
Inguinal hernia	0/154 (0%)		1/156 (0.6%)
Intestinal obstruction	0/154 (0%)		1/156 (0.6%)
Spigelian hernia	0/154 (0%)		1/156 (0.6%)
Vomiting	0/154 (0%)		1/156 (0.6%)
General disorders
Systemic inflammatory response syndrome	1/154 (0.6%)		0/156 (0%)
Hernia	0/154 (0%)		1/156 (0.6%)
Hepatobiliary disorders
Cholecystitis	1/154 (0.6%)		1/156 (0.6%)
Cholecystitis chronic	1/154 (0.6%)		0/156 (0%)
Cholangitis	0/154 (0%)		1/156 (0.6%)
Infections and infestations
Pneumonia	3/154 (1.9%)		3/156 (1.9%)
Arthritis bacterial	1/154 (0.6%)		0/156 (0%)
Bacterial pyelonephritis	1/154 (0.6%)		0/156 (0%)
Bronchitis	1/154 (0.6%)		1/156 (0.6%)
Cellulitis	1/154 (0.6%)		0/156 (0%)
Septic shock	1/154 (0.6%)		0/156 (0%)
Urinary tract infection	1/154 (0.6%)		1/156 (0.6%)
Diverticulitis	0/154 (0%)		1/156 (0.6%)
Erysipelas	0/154 (0%)		1/156 (0.6%)
Gastroenteritis	0/154 (0%)		1/156 (0.6%)
Pneumonia viral	0/154 (0%)		1/156 (0.6%)
Sepsis	0/154 (0%)		1/156 (0.6%)
Staphylococcal bacteraemia	0/154 (0%)		1/156 (0.6%)
Upper respiratory tract infection	0/154 (0%)		1/156 (0.6%)
Injury, poisoning and procedural complications
Fall	2/154 (1.3%)		2/156 (1.3%)
Fractured sacrum	1/154 (0.6%)		0/156 (0%)
Hip fracture	1/154 (0.6%)		0/156 (0%)
Pelvic fracture	1/154 (0.6%)		1/156 (0.6%)
Procedural intestinal perforation	1/154 (0.6%)		0/156 (0%)
Upper limb fracture	1/154 (0.6%)		0/156 (0%)
Ankle fracture	0/154 (0%)		1/156 (0.6%)
Flail chest	0/154 (0%)		1/156 (0.6%)
Laceration	0/154 (0%)		1/156 (0.6%)
Rib fracture	0/154 (0%)		1/156 (0.6%)
Spinal compression fracture	0/154 (0%)		2/156 (1.3%)
Tendon rupture	0/154 (0%)		1/156 (0.6%)
Thoracic vertebral fracture	0/154 (0%)		2/156 (1.3%)
Traumatic haemothorax	0/154 (0%)		1/156 (0.6%)
Investigations
C-reactive protein increased	1/154 (0.6%)		0/156 (0%)
Haemoglobin decreased	0/154 (0%)		1/156 (0.6%)
Metabolism and nutrition disorders
Dehydration	1/154 (0.6%)		1/156 (0.6%)
Lactic acidosis	1/154 (0.6%)		0/156 (0%)
Hypokalaemia	0/154 (0%)		1/156 (0.6%)
Musculoskeletal and connective tissue disorders
Bursitis	2/154 (1.3%)		0/156 (0%)
Acquired claw toe	1/154 (0.6%)		0/156 (0%)
Arthritis	1/154 (0.6%)		0/156 (0%)
Foot deformity	1/154 (0.6%)		0/156 (0%)
Joint range of motion decreased	1/154 (0.6%)		0/156 (0%)
Osteoarthritis	1/154 (0.6%)		2/156 (1.3%)
Arthralgia	0/154 (0%)		1/156 (0.6%)
Back pain	0/154 (0%)		1/156 (0.6%)
Osteoporosis	0/154 (0%)		1/156 (0.6%)
Spondylolisthesis	0/154 (0%)		1/156 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/154 (1.3%)		2/156 (1.3%)
Squamous cell carcinoma	2/154 (1.3%)		0/156 (0%)
Squamous cell carcinoma of skin	2/154 (1.3%)		1/156 (0.6%)
Adenocarcinoma gastric	1/154 (0.6%)		0/156 (0%)
Desmoplastic melanoma	1/154 (0.6%)		0/156 (0%)
Gastrointestinal melanoma	1/154 (0.6%)		0/156 (0%)
Lip neoplasm malignant stage unspecified	1/154 (0.6%)		0/156 (0%)
Metastases to peritoneum	1/154 (0.6%)		0/156 (0%)
Renal cell carcinoma	1/154 (0.6%)		0/156 (0%)
Small intestine adenocarcinoma	1/154 (0.6%)		0/156 (0%)
Adrenal gland cancer	0/154 (0%)		1/156 (0.6%)
B-cell lymphoma	0/154 (0%)		1/156 (0.6%)
Breast cancer	0/154 (0%)		1/156 (0.6%)
Malignant neoplasm of unknown primary site	0/154 (0%)		1/156 (0.6%)
Nervous system disorders
Brain stem ischaemia	1/154 (0.6%)		0/156 (0%)
Presyncope	1/154 (0.6%)		0/156 (0%)
Cerebral infarction	0/154 (0%)		1/156 (0.6%)
Cerebrovascular accident	0/154 (0%)		1/156 (0.6%)
Dementia alzheimer's type	0/154 (0%)		1/156 (0.6%)
Encephalopathy	0/154 (0%)		1/156 (0.6%)
Product Issues
Device dislocation	0/154 (0%)		1/156 (0.6%)
Psychiatric disorders
Alcohol withdrawal syndrome	1/154 (0.6%)		0/156 (0%)
Delirium	0/154 (0%)		1/156 (0.6%)
Renal and urinary disorders
Renal impairment	1/154 (0.6%)		0/156 (0%)
Bladder outlet obstruction	0/154 (0%)		1/156 (0.6%)
Renal failure	0/154 (0%)		1/156 (0.6%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/154 (0%)		2/156 (1.3%)
Uterine prolapse	0/154 (0%)		1/156 (0.6%)
Vaginal prolapse	0/154 (0%)		1/156 (0.6%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/154 (0.6%)		2/156 (1.3%)
Acute respiratory failure	0/154 (0%)		1/156 (0.6%)
Asthma	0/154 (0%)		1/156 (0.6%)
Pulmonary oedema	0/154 (0%)		1/156 (0.6%)
Respiratory failure	0/154 (0%)		2/156 (1.3%)
Skin and subcutaneous tissue disorders
Intertrigo	0/154 (0%)		1/156 (0.6%)
Skin ulcer	0/154 (0%)		1/156 (0.6%)
Vascular disorders
Hypertensive crisis	1/154 (0.6%)		1/156 (0.6%)
Hypotension	1/154 (0.6%)		0/156 (0%)
Peripheral artery aneurysm	1/154 (0.6%)		0/156 (0%)
Thrombophlebitis superficial	1/154 (0.6%)		0/156 (0%)
Varicose vein	1/154 (0.6%)		1/156 (0.6%)
Other (Not Including Serious) Adverse Events
	400 µg Brimonidine Implant		Sham
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/154 (51.3%)		61/156 (39.1%)
Eye disorders
Vitreous floaters	29/154 (18.8%)		1/156 (0.6%)
Conjunctival haemorrhage	21/154 (13.6%)		11/156 (7.1%)
Visual impairment	12/154 (7.8%)		6/156 (3.8%)
Eye pain	11/154 (7.1%)		9/156 (5.8%)
Visual acuity reduced	9/154 (5.8%)		6/156 (3.8%)
Dry eye	8/154 (5.2%)		6/156 (3.8%)
Ocular discomfort	8/154 (5.2%)		1/156 (0.6%)
Infections and infestations
Nasopharyngitis	12/154 (7.8%)		12/156 (7.7%)
Urinary tract infection	3/154 (1.9%)		15/156 (9.6%)
Injury, poisoning and procedural complications
Fall	5/154 (3.2%)		10/156 (6.4%)
Nervous system disorders
Headache	8/154 (5.2%)		4/156 (2.6%)
Vascular disorders
Hypertension	8/154 (5.2%)		11/156 (7.1%)

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.