Safety and Exploratory Efficacy Study of SF0166 for the T... | NCT02914613

Label	Type	Description	Intervention Names
SF0166 low dose BID	Experimental	SF0166 low dose instilled in study eye BID for 28 days of treatment.	Drug: SF0166 Topical Ophthalmic Solution
SF0166 high dose BID	Experimental	SF0166 high dose instilled in study eye BID for 28 days of treatment.	Drug: SF0166 Topical Ophthalmic Solution

Name	Type	Description	Arm Group Labels	Other Names
SF0166 Topical Ophthalmic Solution	Drug		SF0166 high dose BID SF0166 low dose BID	OTT166 Ophthalmic Solution

Measure	Description	Time Frame
Number of Subjects With No Cells Observed Following Slit Lamp Examination From Baseline to Week 8	Percentage of subjects with red blood cell counts in the anterior chamber in the ranges from 0 to > 30 with the higher number being worse	Baseline, 2, 4, 6, and 8 weeks
Number of Subjects With Flare Observed Following Slit Lamp Examination From Baseline to Week 8	Number and percentage of subjects with flare in the anterior chamber graded on a scale from 0 (none) to 4 (severe).	Baseline, 2, 4, 6, and 8 weeks
Number of Subjects With Hyphema Observed Following Slit Lamp Examination From Baseline to Week 8	Number and percentage of subjects with hyphema	Baseline, 2, 4, 6 and 8 weeks
Number of Subjects With Bulbar Conjunctival Injection Observed Following Slit Lamp Examination From Baseline to Week 8	Number and percentage of subjects with bulbar conjunctival injection	Baseline, 2,4,6 and 8 weeks
Number of Subjects With Erythema Observed Following Slit Lamp Examination From Baseline to Week 8	Number and percentage of subjects with erythema	Baseline, 2, 4, 6 and 8 weeks
Number of Subjects With Edema Observed Following Slit Lamp Examination From Baseline to Week 8	Number and percentage of subjects with edema	Baseline, 2,4, 6 and 8 weeks
Number of Subjects With Any Lens Opacity Observed Following Slit Lamp Examination From Baseline to Week 8

Measure	Description	Time Frame
Change in Best-corrected Visual Acuity (BCVA) for Study Eye From Baseline (Day 0) at Week 4 and Week 8		2, 4, 6 and 8 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, 18 years of age or older.
Retinal thickening secondary to type 1 or type 2 diabetes mellitus with Diabetic Macular Edema (DME) defined as central subfield thickness ≥325 microns (µm) on spectral domain OCT in the study eye.
Best-corrected Visual Acuity (BCVA) between 78 and 25 letters, inclusive, in the study eye at the screening/randomization visit using Early Treatment Diabetic Retinopathy Study (ETDRS) testing, with BCVA decrement primarily attributable to Diabetic Macular Edema (DME).
Treatment naïve (i.e., no previous anti--vascular endothelial growth factor [VEGF] treatment in the study eye) or previously treated study eye with adequate washout defined below:
1. Lucentis (ranibizumab): 30-day washout
2. Avastin (bevacizumab): 30-day washout
3. Eylea (aflibercept): 60-day washout
4. Macugen (pegaptanib): 45-day washout
Willing and able to return for all study visits.
Able to adhere to the study dosing requirements.
Understands and signs the written informed consent form.

Exclusion Criteria:

Active proliferative diabetic retinopathy (PDR) in the study eye, such as neovascularization of the optic disc (NVD), neovascularization elsewhere (NVE), vitreous hemorrhage, or neovascular glaucoma.
Uncontrolled glaucoma or ocular hypertension in the study eye defined as an intraocular pressure (IOP) >25 millimeter of mercury (mmHg) regardless of concomitant treatment with IOP-lowering medications.
Uncontrolled hypertension defined as systolic >180 mmHg or >160 mmHg on 2 consecutive measurements (during the same visit) or diastolic >100 mmHg on optimal medical regimen.
Screening glycated hemoglobin (HbA1c) blood test >12.0%.
Previous panretinal photocoagulation (PRP) in the study eye within 4 months of study enrollment, or the need for PRP during the study based on the Investigator's opinion.
Previous focal laser photocoagulation in the study eye, within the foveal avascular zone.
Intravitreal/periocular/topical ocular steroids of any type in the study eye within 90 days (3 months) prior to study enrollment.
Placement of Iluvien or Retisert (fluocinolone acetonide intravitreal implant) in the study eye within 36 months (3 years) prior to study enrollment.
Use of Ozurdex (dexamethasone intravitreal implant) in the study eye within 180 days (6 months) prior to study enrollment.
Significant epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular traction in the study eye as determined by the optical coherence tomography (OCT) results.
Previous pars plana vitrectomy in the study eye.
Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrollment.
Yttrium aluminium garnet (YAG) laser treatment in the study eye within 30 days (1 month) prior to study enrollment.
Concomitant use of any topical ophthalmic medications in the study eye, including dry eye or glaucoma medications, unless on a stable dose for at least 90 days (3 months) prior to study enrollment and expected to stay on stable dose throughout study participation. Artificial tears are allowed.
High myopia in the study eye, with a spherical equivalent of >8.00 Diopters (D) at screening.
Chronic or recurrent uveitis in the study eye.
Ongoing ocular infection or inflammation in either eye.
A history of cataract surgery complicated by vitreous loss in the study eye.
Congenital eye malformations in the study eye.
A history of penetrating ocular trauma in the study eye.
Mentally handicapped.
Females of childbearing potential (i.e., who are not postmenopausal for at least 1 year or surgically sterile for at least 6 weeks prior to Visit 1 - Screening/Randomization) who are lactating, or who are pregnant as determined by a positive urine pregnancy test (UPT) at Visit 1 - Screening/Randomization. Women of childbearing potential must agree to use acceptable methods of birth control throughout the study. Acceptable methods of birth control include tubal ligation, transdermal patch, intrauterine devices/systems, oral/implantable/injectable or contraceptives, sexual abstinence, double barrier method, or vasectomized partner.
Participation in any other investigational device or drug clinical research study within 30 days of Visit 1 - Screening/Randomization.
Contraindication to the study medications or fluorescein dye.
Other ocular pathologies that in the Investigator's opinion would interfere with the subject's vision in the study eye.

Name	Affiliation	Role
Gary Foulks, MD	Medical Monitor	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Retina-Vitreous Associates Medical Group		Beverly Hills	California	90211	United States
United Medical Research Institute

ID	Title	Description
FG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
FG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Nov 22, 2016

ID	Title	Description
BG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
BG001	SF0166 High Dose 5% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00022 BG00122 BG00244

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Subjects With No Cells Observed Following Slit Lamp Examination From Baseline to Week 8

Percentage of subjects with red blood cell counts in the anterior chamber in the ranges from 0 to > 30 with the higher number being worse

The analysis population at Baseline includes all randomized participants, 22 in each group. Before Week 2, there were two discontinuations, one in each group. Before Week 4 there was one discontinuation in the high dose 5.0% group. One participant in each dose group missed the Week 4 visit. Prior to Week 6 there was one discontinuation in the low dose 2.5% group. One low dose 2.5% group participant missed the Week 6 visit. At Week 8, all the non-discontinued were assessed, 20 in each dose group.

Posted

Count of Participants

Participants

Baseline, 2, 4, 6, and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants	OG00022 OG00122

Title

Denominators

Categories

Baseline (Study Eye) - No cells seen

- ParticipantsOG00022
- ParticipantsOG00122

Title	Measurements
	OG00022

Primary

Number of Subjects With Flare Observed Following Slit Lamp Examination From Baseline to Week 8

Number and percentage of subjects with flare in the anterior chamber graded on a scale from 0 (none) to 4 (severe).

Posted

Count of Participants

Participants

Baseline, 2, 4, 6, and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0 % instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Hyphema Observed Following Slit Lamp Examination From Baseline to Week 8

Number and percentage of subjects with hyphema

Posted

Count of Participants

Participants

Baseline, 2, 4, 6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Bulbar Conjunctival Injection Observed Following Slit Lamp Examination From Baseline to Week 8

Number and percentage of subjects with bulbar conjunctival injection

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Erythema Observed Following Slit Lamp Examination From Baseline to Week 8

Number and percentage of subjects with erythema

Posted

Count of Participants

Participants

Baseline, 2, 4, 6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Edema Observed Following Slit Lamp Examination From Baseline to Week 8

Number and percentage of subjects with edema

Posted

Count of Participants

Participants

Baseline, 2,4, 6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Any Lens Opacity Observed Following Slit Lamp Examination From Baseline to Week 8

Number and percentage of subjects with any lens opacity

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Abnormal Findings in Optic Nerve Following Fundus Examination From Baseline to Week 8

Number and percentage of subjects with abnormal findings in the optic nerve

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Abnormal Findings in Vitreous Following Fundus Examination From Baseline to Week 8

Number and percentage of subjects (both eyes) with abnormal findings in the vitreous

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Abnormal Findings in Fundus Following Fundus Examination From Baseline to Week 8

Number and percentage of subjects with abnormal findings in the fundus

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Abnormal Findings in Macula/Choroid Following Fundus Examination From Baseline to Week 8

Number and percentage of subjects with abnormal findings in the macula/choroid

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Abnormal Findings in Vessels Following Fundus Examination From Baseline to Week 8

Number and percentage of subjects with abnormal findings in the retinal vessels

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Cup:Disc Ratio of Subjects Following Fundus Examination From Baseline to Week 8

Number and percentage of subjects with specified Cup:Disc ratio in the range from 0.1 to 0.6 with the higher number being worse

Posted

Count of Participants

Participants

Baseline, 2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Number of Subjects With Abnormal Findings Following A Fluorescein Angiogram at Week 4 Compared to Baseline (Day 0)

Number and percentage of subjects with abnormal fluorescein angiogram findings

The analysis population at Baseline includes all randomized participants, 22 in each group. The only planned subsequent assessment was at Week 4, end of treatment.

Posted

Count of Participants

Participants

Baseline and 4 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants	OG000

Primary

Change in Intraocular Pressure From Baseline to Week 8

Mean and standard deviation of change from Baseline in intra-ocular pressure

Posted

Mean

Standard Deviation

mmHg

2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Primary

Change in Central Retinal Thickness (CRT) for Study Eye From Baseline (Day 0) to Week 8

The analysis population is the per protocol population with 19 participants in each dose group at Baseline. One participant in each group missed the Week 4 visit and one participant in the low dose 2.5% group missed the Week 6 visit. Four participants, three in the low dose group and one in the high dose group, were administered rescue medication at clinic visits and their data from subsequent visits are excluded. One participant in each dose group was excluded for having an out-of-window visit.

Posted

Mean

Standard Deviation

change from baseline

2,4,6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% will be instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% will be instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Secondary

Change in Best-corrected Visual Acuity (BCVA) for Study Eye From Baseline (Day 0) at Week 4 and Week 8

Posted

Mean

Standard Deviation

change from baseline

2, 4, 6 and 8 weeks

ID	Title	Description
OG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% will be instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution
OG001	SF0166 High Dose 5% BID	SF0166 high dose 5.0% will be instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypercoagulation	Blood and lymphatic system disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Atrial flutter	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Cardiomyopathy	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected22 at risk EG0011 affected22 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0011 affected22 at risk
Vitreous haemorrhage	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Blepharitis	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected22 at risk EG0012 affected22 at risk
Cataract	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected22 at risk EG0012 affected22 at risk
Ocular hyperaemia	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected22 at risk EG0012 affected22 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Non-cardiac chest pain	General disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Unevaluable event	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Hypersensitivity	Immune system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Cellulitis	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Oral candidiasis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Pharyngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Pneumonia	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Sepsis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Sinusitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Urinary tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Wound	Injury, poisoning and procedural complications	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Foot fracture	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected22 at risk EG0011 affected22 at risk
Blood potassium increased	Investigations	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected22 at risk EG0011 affected22 at risk
Dizziness	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Anxiety	Psychiatric disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected22 at risk EG0010 affected22 at risk
Hypertension	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected22 at risk EG0012 affected22 at risk

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SF0166 Low Dose 2.5% BID	SF0166 low dose 2.5% will be instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution	0	22	5	22	10	22
EG001	SF0166 High Dose 5.0% BID	SF0166 high dose 5.0% will be instilled in study eye BID for 28 days of treatment. SF0166 Topical Ophthalmic Solution	0	22	1	22	4	22