GATE: Geographic Atrophy Treatment Evaluation

• Sponsor: Alcon Research (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00890097
• Collaborator: (none)
• Enrollment: 772
• Arms: 3
• Duration (Months): 37

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of AL-8309B Ophthalmic Solution versus Vehicle administered as a topical ocular drop for the treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Condition or Disease	Intervention/Treatment	Phase
Geographic Atrophy; Age-Related Macular Degeneration	Drug: AL-8309B Ophthalmic Solution; Drug: AL-8309B Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 772 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Safety and Efficacy of AL-8309B Ophthalmic Solution for the Treatment of Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AL-8309B 1.0% AL-8309B 1.0% Ophthalmic Solution, 1 drop in each eye twice daily for 30 months, up to a maximum of 36 months	Drug: AL-8309B Ophthalmic Solution
Experimental: AL-8309B 1.75% AL-8309B 1.75% Ophthalmic Solution, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months	Drug: AL-8309B Ophthalmic Solution
Placebo Comparator: Vehicle AL-8309B Vehicle, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months	Drug: AL-8309B Vehicle; Inactive ingredients used as placebo comparator

Outcome Measures

Primary Outcome Measures

1. Mean Annualized Lesion Enlargement Rate From Baseline as Assessed With Fundus Autofluorescence Imaging [Baseline, up to Month 30]

   The size of the retinal lesion was measured using the Heidelberg Retinal Angiography system at Baseline, Month 6, Month 12, Month 15, Month 18, Month 24, and Month 30. Images were collected in both eyes; however, one eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. Results were estimated from a longitudinal random effects regression model. A greater lesion growth rate may indicate a faster progression of the disease.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Willing to give written informed consent, make required study visits, and follow instructions.

• Able to administer eye drops or have a caretaker to administer the eye drops.

• Study eye: Atrophy secondary to age-related macular degeneration, best corrected visual acuity (BCVA) of 35 letters (20/200 Snellen equivalent) or better, clear ocular media, and adequate pupillary dilation.

• Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

• Pregnant, nursing, or not using adequate contraception.

• Ocular disease in the study eye, other than non-exudative AMD.

• History of cataract surgery in either eye within the past 3 months of screening.

• History or evidence of serious ocular trauma or intraocular surgery in either eye within the past 6 months of screening.

• Any medical condition that would make participation in the trial or adherence to the study schedule difficult or unlikely.

• Participation in an investigational drug or device study within 30 days of screening.

• Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Sally Scheib, Sr. Clinical Lead, Alcon Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT00890097
• Other Study ID Numbers: C-08-36
• First Posted: Apr 29, 2009
• Last Update Posted: Jul 3, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Alcon Research: Geographic Atrophy; GA; Age-Related Macular Degeneration; AMD
• Additional relevant MeSH terms: Macular Degeneration; Geographic Atrophy; Atrophy; Ophthalmic Solutions

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 48 study centers located in 14 countries.
Pre-assignment Detail	This reporting group includes all enrolled subjects (772). A subject was considered enrolled if they met all of the inclusion criteria and none of the exclusion criteria.

Arm/Group Title	AL-8309B 1.0%	AL-8309B 1.75%	Vehicle
Arm/Group Description	AL-8309B 1.0% Ophthalmic Solution, 1 drop in each eye twice daily for 30 months, up to a maximum of 36 months	AL-8309B 1.75% Ophthalmic Solution, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months	AL-8309B Vehicle, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months
Period Title: Overall Study
STARTED	252	259	261
COMPLETED	184	173	184
NOT COMPLETED	68	86	77

Baseline Characteristics

Arm/Group Title	AL-8309B 1.0%	AL-8309B 1.75%	Vehicle	Total
Arm/Group Description	AL-8309B 1.0% Ophthalmic Solution, 1 drop in each eye twice daily for 30 months, up to a maximum of 36 months	AL-8309B 1.75% Ophthalmic Solution, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months	AL-8309B Vehicle, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months	Total of all reporting groups
Overall Participants	252	259	261	772
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	77.9 (8.0)	78.3 (7.7)	78.8 (7.1)	78.3 (7.6)
Sex: Female, Male (Count of Participants)
Female	130 51.6%	162 62.5%	147 56.3%	439 56.9%
Male	122 48.4%	97 37.5%	114 43.7%	333 43.1%
Region of Enrollment (participants) [Number]
United States	111 44%	112 43.2%	116 44.4%	339 43.9%
France	28 11.1%	27 10.4%	29 11.1%	84 10.9%
Switzerland	21 8.3%	21 8.1%	21 8%	63 8.2%
Germany	18 7.1%	20 7.7%	19 7.3%	57 7.4%
Australia	16 6.3%	18 6.9%	16 6.1%	50 6.5%
Israel	13 5.2%	15 5.8%	15 5.7%	43 5.6%
Italy	12 4.8%	15 5.8%	14 5.4%	41 5.3%
Austria	13 5.2%	13 5%	14 5.4%	40 5.2%
Belgium	7 2.8%	6 2.3%	6 2.3%	19 2.5%
United Kingdom	4 1.6%	3 1.2%	3 1.1%	10 1.3%
Ireland	3 1.2%	3 1.2%	3 1.1%	9 1.2%
Japan	3 1.2%	2 0.8%	3 1.1%	8 1%
Portugal	2 0.8%	3 1.2%	2 0.8%	7 0.9%
Canada	1 0.4%	1 0.4%	0 0%	2 0.3%

Outcome Measures

1. Primary Outcome

Title	Mean Annualized Lesion Enlargement Rate From Baseline as Assessed With Fundus Autofluorescence Imaging
Description	The size of the retinal lesion was measured using the Heidelberg Retinal Angiography system at Baseline, Month 6, Month 12, Month 15, Month 18, Month 24, and Month 30. Images were collected in both eyes; however, one eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. Results were estimated from a longitudinal random effects regression model. A greater lesion growth rate may indicate a faster progression of the disease.
Time Frame	Baseline, up to Month 30

Outcome Measure Data

Analysis Population Description

This analysis population included all treated subjects. A subject was considered treated if they had a first or last dosing date in the database.

Arm/Group Title	AL-8309B 1.0%	AL-8309B 1.75%	Vehicle
Arm/Group Description	AL-8309B 1.0% Ophthalmic Solution, 1 drop in each eye twice daily for 30 months, up to a maximum of 36 months	AL-8309B 1.75% Ophthalmic Solution, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months	AL-8309B Vehicle, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months
Measure Participants	250	258	260
Mean (95% Confidence Interval) [square millimeters per year]	1.725	1.758	1.707

Adverse Events

Time Frame	Adverse events were collected for the duration of the study (3 years, 2 month). Adverse events were obtained as solicited comments from the study subjects and as observations by the study Investigator as outlined in the study protocol.
Adverse Event Reporting Description	This analysis population includes all treated subjects (768).
Arm/Group Title	AL-8309B 1.0%		AL-8309B 1.75%		Vehicle
Arm/Group Description	AL-8309B 1.0% Ophthalmic Solution, 1 drop in each eye twice daily for 30 months, up to a maximum of 36 months		AL-8309B 1.75% Ophthalmic Solution, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months		AL-8309B Vehicle, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months
All Cause Mortality
	AL-8309B 1.0%		AL-8309B 1.75%		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AL-8309B 1.0%		AL-8309B 1.75%		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/250 (34.4%)		96/258 (37.2%)		85/260 (32.7%)
Blood and lymphatic system disorders
Anaemia	1/250 (0.4%)		3/258 (1.2%)		0/260 (0%)
Iron deficiency anaemia	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Cardiac disorders
Acute coronary syndrome	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Angina pectoris	4/250 (1.6%)		3/258 (1.2%)		1/260 (0.4%)
Angina unstable	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Arrhythmia	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Arrhythmia supraventricular	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Atrial fibrillation	4/250 (1.6%)		3/258 (1.2%)		5/260 (1.9%)
Atrial flutter	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Atrioventricular block complete	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Atrioventricular block second degree	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Bundle branch block	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Cardiac arrest	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Cardiac disorder	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Cardiac failure	2/250 (0.8%)		4/258 (1.6%)		0/260 (0%)
Cardiac failure acute	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Cardiac failure congestive	4/250 (1.6%)		3/258 (1.2%)		1/260 (0.4%)
Coronary artery disease	0/250 (0%)		2/258 (0.8%)		1/260 (0.4%)
Coronary artery occlusion	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Myocardial infarction	4/250 (1.6%)		0/258 (0%)		0/260 (0%)
Myocardial ischaemia	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Sick sinus syndrome	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Sinus arrhythmia	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Tachycardia	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Ventricular tachycardia	0/250 (0%)		0/258 (0%)		2/260 (0.8%)
Congenital, familial and genetic disorders
Choledochal cyst	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Endocrine disorders
Goitre	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Eye disorders
Cataract	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Macular oedema	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Retinal artery occlusion	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Retinal detachment	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Visual acuity reduced	1/250 (0.4%)		1/258 (0.4%)		3/260 (1.2%)
Gastrointestinal disorders
Abdominal pain	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Diarrhoea	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Gastritis	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Gastrointestinal haemorrhage	1/250 (0.4%)		2/258 (0.8%)		0/260 (0%)
Haematemesis	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Inguinal hernia	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Intestinal obstruction	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Intra-abdominal haematoma	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Intussusception	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Nausea	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Pancreatitis	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Pancreatitis acute	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Rectal haemorrhage	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Retroperitoneal haemorrhage	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Small intestinal obstruction	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Umbilical hernia	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Vomiting	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
General disorders
Asthenia	1/250 (0.4%)		0/258 (0%)		2/260 (0.8%)
Chest discomfort	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Chest pain	3/250 (1.2%)		1/258 (0.4%)		0/260 (0%)
Death	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
General physical health deterioration	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Impaired healing	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Inflammation	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Non-cardiac chest pain	1/250 (0.4%)		0/258 (0%)		1/260 (0.4%)
Pain	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Pyrexia	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Hepatobiliary disorders
Bile duct stone	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Biliary tract disorder	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Cholangitis	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Cholecystitis acute	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Cirrhosis alcoholic	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Hepatic cirrhosis	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Immune system disorders
Anaphylactic shock	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Infections and infestations
Appendicitis	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Bronchitis	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Cellulitis	1/250 (0.4%)		0/258 (0%)		1/260 (0.4%)
Dacryocystitis	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Diverticulitis	4/250 (1.6%)		0/258 (0%)		0/260 (0%)
Echinococciasis	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Gastroenteritis	1/250 (0.4%)		0/258 (0%)		2/260 (0.8%)
Gastroenteritis viral	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Labyrinthitis	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Lobar pneumonia	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Localised infection	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Lower respiratory tract infection	0/250 (0%)		0/258 (0%)		2/260 (0.8%)
Lung infection	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Pancreatic abscess	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Pneumonia	3/250 (1.2%)		9/258 (3.5%)		5/260 (1.9%)
Pyelonephritis acute	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Sepsis	1/250 (0.4%)		3/258 (1.2%)		1/260 (0.4%)
Sinusitis	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Urinary tract infection	0/250 (0%)		3/258 (1.2%)		1/260 (0.4%)
Urosepsis	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Arthropod bite	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Fall	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Injury	16/250 (6.4%)		14/258 (5.4%)		15/260 (5.8%)
Intraocular lens dislocation	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Overdose	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Post procedural complication	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Skin laceration	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Subdural haematoma	1/250 (0.4%)		0/258 (0%)		1/260 (0.4%)
Investigations
Arthroscopy	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Catheterisation cardiac	2/250 (0.8%)		1/258 (0.4%)		1/260 (0.4%)
Endoscopy	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Investigation	0/250 (0%)		0/258 (0%)		2/260 (0.8%)
Oxygen saturation decreased	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Renal function test abnormal	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Metabolism and nutrition disorders
Dehydration	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Hyponatraemia	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/250 (0.4%)		0/258 (0%)		2/260 (0.8%)
Arthritis	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Costochondritis	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Intervertebral disc degeneration	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Intervertebral disc disorder	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Intervertebral disc protrusion	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Kyphosis	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Musculoskeletal chest pain	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Osteoarthritis	2/250 (0.8%)		5/258 (1.9%)		2/260 (0.8%)
Osteoporosis	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Osteoporotic fracture	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Rheumatoid arthritis	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Rotator cuff syndrome	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Spinal column stenosis	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Temporomandibular joint syndrome	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Bladder cancer	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Breast cancer	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Breast cancer metastatic	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Bronchial carcinoma	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Cardiac valve fibroelastoma	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Colon cancer metastatic	1/250 (0.4%)		0/258 (0%)		1/260 (0.4%)
Endometrial cancer	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Hepatic neoplasm malignant non-resectable	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Lung adenocarcinoma stage III	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Lung adenocarcinoma stage IV	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Lung neoplasm malignant	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Malignant melanoma	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Metastases to abdominal cavity	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Metastases to central nervous system	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Metastases to lung	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Multiple myeloma	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Myelodysplastic syndrome	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Neoplasm malignant	3/250 (1.2%)		1/258 (0.4%)		0/260 (0%)
Pancreatic carcinoma non-resectable	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Parathyroid tumour benign	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Prostate cancer	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Renal cell carcinoma	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Squamous cell carcinoma of skin	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Thyroid adenoma	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Thyroid neoplasm	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Ureteric cancer metastatic	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Nervous system disorders
Altered state of consciousness	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Carpal tunnel syndrome	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Cerebral artery occlusion	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Cerebral haematoma	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Cerebral haemorrhage	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Cerebrovascular accident	3/250 (1.2%)		4/258 (1.6%)		3/260 (1.2%)
Convulsion	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Dementia	1/250 (0.4%)		0/258 (0%)		1/260 (0.4%)
Dizziness	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Dysarthria	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Extrapyramidal disorder	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Grand mal convulsion	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Haemorrhage intracranial	0/250 (0%)		0/258 (0%)		2/260 (0.8%)
Headache	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Ischaemic stroke	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Loss of consciousness	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Nerve compression	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Parkinson's disease	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Sciatica	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Subarachnoid haemorrhage	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Syncope	1/250 (0.4%)		2/258 (0.8%)		2/260 (0.8%)
Syringomyelia	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Transient ischaemic attack	4/250 (1.6%)		2/258 (0.8%)		2/260 (0.8%)
Psychiatric disorders
Confusional state	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Depression	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Depression suicidal	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Disorientation	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Hallucination, visual	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Major depression	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Mental status changes	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Schizophrenia	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Renal and urinary disorders
Bladder disorder	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Haematuria	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Hydronephrosis	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Nephrolithiasis	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Pelvi-ureteric obstruction	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Renal failure	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Renal failure acute	1/250 (0.4%)		1/258 (0.4%)		1/260 (0.4%)
Renal failure chronic	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Urinary retention	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/250 (0.4%)		3/258 (1.2%)		1/260 (0.4%)
Ovarian cyst	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Prostatomegaly	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Vaginal fistula	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/250 (0%)		0/258 (0%)		3/260 (1.2%)
Atelectasis	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Chronic obstructive pulmonary disease	1/250 (0.4%)		4/258 (1.6%)		1/260 (0.4%)
Dyspnoea	2/250 (0.8%)		1/258 (0.4%)		0/260 (0%)
Dyspnoea exertional	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Hypoxia	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Lung disorder	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Pneumonia aspiration	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Pulmonary congestion	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Pulmonary embolism	1/250 (0.4%)		0/258 (0%)		3/260 (1.2%)
Respiratory acidosis	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Respiratory arrest	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Respiratory failure	0/250 (0%)		0/258 (0%)		2/260 (0.8%)
Sleep apnoea syndrome	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Surgical and medical procedures
Angioplasty	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Aortic aneurysm repair	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Aortic valve repair	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Aortic valve replacement	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Appendicectomy	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Bunion operation	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Cardiac pacemaker insertion	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Cardioversion	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Haemorrhoid operation	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Hip arthroplasty	0/250 (0%)		2/258 (0.8%)		1/260 (0.4%)
Hip surgery	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Inguinal hernia repair	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Intraocular lens implant	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Intrathecal pump insertion	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Joint arthroplasty	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Keratoplasty	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Knee arthroplasty	2/250 (0.8%)		1/258 (0.4%)		0/260 (0%)
Knee operation	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Malignant tumour excision	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Radiotherapy to eye	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Salivary gland operation	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Scoliosis surgery	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Spinal operation	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Vasodilation procedure	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Vascular disorders
Aortic aneurysm	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Aortic stenosis	1/250 (0.4%)		1/258 (0.4%)		0/260 (0%)
Arterial occlusive disease	0/250 (0%)		1/258 (0.4%)		1/260 (0.4%)
Circulatory collapse	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Deep vein thrombosis	2/250 (0.8%)		0/258 (0%)		0/260 (0%)
Haemorrhage	0/250 (0%)		1/258 (0.4%)		0/260 (0%)
Hypertension	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Hypertensive crisis	0/250 (0%)		2/258 (0.8%)		0/260 (0%)
Hypotension	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Peripheral arterial occlusive disease	1/250 (0.4%)		0/258 (0%)		0/260 (0%)
Peripheral vascular disorder	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Temporal arteritis	0/250 (0%)		0/258 (0%)		1/260 (0.4%)
Other (Not Including Serious) Adverse Events
	AL-8309B 1.0%		AL-8309B 1.75%		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	207/250 (82.8%)		212/258 (82.2%)		207/260 (79.6%)
Eye disorders
Blepharitis	15/250 (6%)		19/258 (7.4%)		7/260 (2.7%)
Cataract	30/250 (12%)		23/258 (8.9%)		23/260 (8.8%)
Choroidal neovascularisation	20/250 (8%)		20/258 (7.8%)		16/260 (6.2%)
Eye irritation	20/250 (8%)		27/258 (10.5%)		9/260 (3.5%)
Eye pain	16/250 (6.4%)		21/258 (8.1%)		11/260 (4.2%)
Lacrimation increased	8/250 (3.2%)		15/258 (5.8%)		3/260 (1.2%)
Macular degeneration	18/250 (7.2%)		20/258 (7.8%)		14/260 (5.4%)
Retinal haemorrhage	14/250 (5.6%)		16/258 (6.2%)		21/260 (8.1%)
Visual acuity reduced	101/250 (40.4%)		107/258 (41.5%)		109/260 (41.9%)
Gastrointestinal disorders
Constipation	13/250 (5.2%)		4/258 (1.6%)		13/260 (5%)
Gastrooesophageal reflux disease	15/250 (6%)		11/258 (4.3%)		9/260 (3.5%)
Nausea	15/250 (6%)		8/258 (3.1%)		8/260 (3.1%)
General disorders
Oedema peripheral	14/250 (5.6%)		4/258 (1.6%)		11/260 (4.2%)
Infections and infestations
Bronchitis	15/250 (6%)		21/258 (8.1%)		28/260 (10.8%)
Influenza	7/250 (2.8%)		8/258 (3.1%)		14/260 (5.4%)
Nasopharyngitis	19/250 (7.6%)		19/258 (7.4%)		22/260 (8.5%)
Urinary tract infection	20/250 (8%)		28/258 (10.9%)		19/260 (7.3%)
Injury, poisoning and procedural complications
Injury	34/250 (13.6%)		38/258 (14.7%)		31/260 (11.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/250 (2.4%)		15/258 (5.8%)		9/260 (3.5%)
Back pain	13/250 (5.2%)		12/258 (4.7%)		17/260 (6.5%)
Osteoarthritis	14/250 (5.6%)		21/258 (8.1%)		12/260 (4.6%)
Nervous system disorders
Headache	19/250 (7.6%)		15/258 (5.8%)		9/260 (3.5%)
Psychiatric disorders
Depression	10/250 (4%)		9/258 (3.5%)		18/260 (6.9%)
Vascular disorders
Hypertension	24/250 (9.6%)		30/258 (11.6%)		36/260 (13.8%)

Limitations/Caveats

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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.