Efficacy and Safety Study of Bimatoprost Sustained-Releas... | NCT02247804

NCT02247804

ID	Type	Description	Link
2014-003037-26	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Bimatoprost SR 15 μg	Experimental	Study Eye: bimatoprost sustained release (SR) 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Drug: Bimatoprost SR Drug: Active Comparator: Timolol 0.5% Other: Sham: Applicator Without Needle Drug: Timolol Vehicle (placebo)
Bimatoprost SR 10 μg	Experimental	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Drug: Bimatoprost SR Drug: Active Comparator: Timolol 0.5% Other: Sham: Applicator Without Needle Drug: Timolol Vehicle (placebo)
Timolol 0.5%	Active Comparator	Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Drug: Active Comparator: Timolol 0.5% Other: Sham: Applicator Without Needle

Name	Type	Description	Arm Group Labels	Other Names
Bimatoprost SR	Drug	Bimatoprost SR administered in the study eye on Day 1, Week 16, and Week 32.	Bimatoprost SR 10 μg Bimatoprost SR 15 μg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in IOP in the Study Eye at Week 12 (Hours 0 and 2)	IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. A mixed-effects model with repeated measures (MMRM) was used for analyses. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.	Baseline (Hours 0 and 2) to Week 12 (Hours 0 and 2)
IOP in the Study Eye at Week 2 (Hour 0)	IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.	Week 2 (Hour 0)
IOP in the Study Eye at Week 2 (Hour 2)	IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.	Week 2 (Hour 2)
IOP in the Study Eye at Week 6 (Hour 0)	IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in IOP in the Study Eye	IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.

Eligibility Module

Name	Affiliation	Role
Marina Bejanian	Allergan	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Glaucoma Specialists		Phoenix	Arizona	85050	United States
Lugene Eye Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36378864	Derived	Weinreb RN, Bacharach J, Brubaker JW, Medeiros FA, Bejanian M, Bernstein P, Robinson MR. Bimatoprost Implant Biodegradation in the Phase 3, Randomized, 20-Month ARTEMIS Studies. J Ocul Pharmacol Ther. 2023 Jan-Feb;39(1):55-62. doi: 10.1089/jop.2022.0137. Epub 2022 Nov 15.
35643967	Derived	Medeiros FA, Sheybani A, Shah MM, Rivas M, Bai Z, Werts E, Ahmed IIK, Craven ER. Single Administration of Intracameral Bimatoprost Implant 10 microg in Patients with Open-Angle Glaucoma or Ocular Hypertension. Ophthalmol Ther. 2022 Aug;11(4):1517-1537. doi: 10.1007/s40123-022-00527-6. Epub 2022 May 28.

Label	URL
More Information	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost sustained release (SR) 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Apr 19, 2018	Apr 3, 2020

Arm/Group Information

ID	Title	Description
BG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
BG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
BG002	Timolol 0.5%: Comparator	Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00062.5± 13.0 BG00162.6± 11.5 BG00262.5± 11.0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00096 BG00186 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG000122 BG001123 BG002

Intraocular Pressure (IOP)

Mean

Full Range

mm Hg

Title

Denominators

Categories

Hour 0

Title	Measurements
	BG00024.76(18.0 to 32.0) BG001

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

Change From Baseline in IOP in the Study Eye at Week 12 (Hours 0 and 2)

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. A mixed-effects model with repeated measures (MMRM) was used for analyses. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.

ITT population was defined as all randomized participants. Number analyzed is the number of participants with evaluable data at the given timepoint.

Posted

Least Squares Mean

Standard Error

millimeters of mercury (mm Hg)

Baseline (Hours 0 and 2) to Week 12 (Hours 0 and 2)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG002	Timolol 0.5%: Comparator	Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Units	Counts
Participants	OG000198 OG001198 OG002198

Title

Denominators

Categories

Change from Baseline at Hour 0, Week 12

- ParticipantsOG000185
- ParticipantsOG001192
- ParticipantsOG002191

Title	Measurements

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Change from Baseline Week 12, Hour 0: The null hypothesis was that bimatoprost SR 15 μg was to be declared non-inferior to timolol 0.5% if the upper limit of the 95% CI was ≤ 1.5 mm Hg for all scheduled timepoints (Hours 0 and 2 at Week 12).	MMRM		0.2950		Least-squares Mean Difference	-0.41	Standard Error of the Mean	0.39	2-Sided	95	-1.17	0.36					Non-Inferiority	MMRM analyses was used with response variable:IOP time-matched change from baseline;Fixed factors: Treatment,timepoint,treatment-by-timepoint interaction and baseline IOP stratification;Covariate:Time-matched baseline IOP and timepoint by time-matched baseline IOP interaction. Unstructured covariance matrix was used.

Primary

IOP in the Study Eye at Week 2 (Hour 0)

ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

mm Hg

Week 2 (Hour 0)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Primary

IOP in the Study Eye at Week 2 (Hour 2)

ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

mm Hg

Week 2 (Hour 2)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Primary

IOP in the Study Eye at Week 6 (Hour 0)

ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

mm Hg

Week 6 (Hour 0)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Primary

IOP in the Study Eye at Week 6 (Hour 2)

ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

mm Hg

Week 6 (Hour 2)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Primary

IOP in the Study Eye at Week 12 (Hour 0)

ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

mm Hg

Week 12 (Hour 0)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Primary

IOP in the Study Eye at Week 12 (Hour 2)

ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

mm Hg

Week 12 (Hour 2)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Secondary

Change From Baseline in IOP in the Study Eye

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.

ITT population was defined as all randomized participants. Number analyzed is the number of participants with evaluable data at the given timepoint.

Posted

Least Squares Mean

Standard Error

mm Hg

Baseline (Hours 0 and 2) to Weeks 2 and 6 (Hours 0 and 2)

ID	Title	Description
OG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
OG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bimatoprost SR 15 μg	Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	2	193	31	193	143	193
EG001	Bimatoprost SR 10 μg	Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	1	197	25	197	138	197
EG002	Timolol 0.5%: Comparator	Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	1	197	18	197	105	197

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Cardiac arrest	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Cardiac failure	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Bradycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Corneal endothelial cell loss	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00012 affected193 at risk EG0014 affected197 at risk EG0020 affected197 at risk
Corneal oedema	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected193 at risk EG0012 affected197 at risk EG0020 affected197 at risk
Iridocyclitis	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Corneal touch	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Macular oedema	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Retinal tear	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Ulcerative keratitis	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Uveitis	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Retinal detachment	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Peptic ulcer	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Chest pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Appendicitis perforated	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Diverticulitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Post procedural sepsis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0011 affected197 at risk EG0021 affected197 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0022 affected197 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Chondrocalcinosis pyrophosphate	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0021 affected197 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Joint instability	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0012 affected197 at risk EG0020 affected197 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0021 affected197 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0021 affected197 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Invasive breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Prostate cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0022 affected197 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Embolic stroke	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Trigeminal neuralgia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Sciatica	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
VIth nerve paralysis	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Renal failure	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0011 affected197 at risk EG0021 affected197 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Internal haemorrhage	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Varicose vein	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Hypotension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0011 affected197 at risk EG0020 affected197 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected193 at risk EG0010 affected197 at risk EG0021 affected197 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected193 at risk EG0010 affected197 at risk EG0020 affected197 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Conjunctival hyperaemia	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00074 affected193 at risk EG00160 affected197 at risk EG00247 affected197 at risk
Foreign body sensation in eyes	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00031 affected193 at risk EG00123 affected197 at risk EG00212 affected197 at risk
Eye pain	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00028 affected193 at risk EG00126 affected197 at risk EG00212 affected197 at risk
Eye irritation	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00028 affected193 at risk EG00118 affected197 at risk EG00222 affected197 at risk
Photophobia	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00023 affected193 at risk EG00119 affected197 at risk EG0024 affected197 at risk
Corneal endothelial cell loss	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00020 affected193 at risk EG00114 affected197 at risk EG0020 affected197 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00019 affected193 at risk EG00117 affected197 at risk EG00216 affected197 at risk
Iritis	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00019 affected193 at risk EG00111 affected197 at risk EG0021 affected197 at risk
Dry eye	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00017 affected193 at risk EG00119 affected197 at risk EG00212 affected197 at risk
Punctate keratitis	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00016 affected193 at risk EG00112 affected197 at risk EG00214 affected197 at risk
Lacrimation increased	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00013 affected193 at risk EG00110 affected197 at risk EG00212 affected197 at risk
Vision blurred	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00012 affected193 at risk EG00110 affected197 at risk EG00211 affected197 at risk
Corneal oedema	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00012 affected193 at risk EG0015 affected197 at risk EG0022 affected197 at risk
Anterior chamber cell	Eye disorders	MedDRA 22.0	Systematic Assessment	EG00011 affected193 at risk EG0019 affected197 at risk EG0020 affected197 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG00013 affected193 at risk EG00110 affected197 at risk EG00214 affected197 at risk
Influenza	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0008 affected193 at risk EG00113 affected197 at risk EG0024 affected197 at risk
Intraocular pressure increased	Investigations	MedDRA 22.0	Systematic Assessment	EG00013 affected193 at risk EG00120 affected197 at risk EG0027 affected197 at risk
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0008 affected193 at risk EG00114 affected197 at risk EG0027 affected197 at risk
Visual field defect	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0004 affected193 at risk EG00110 affected197 at risk EG0025 affected197 at risk
Hypertension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG00017 affected193 at risk EG00112 affected197 at risk EG0028 affected197 at risk

ID	Term
D004864	Equipment and Supplies
D011412	Propanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D020005	Propanols
D000588	Amines
D013830	Thiadiazoles
D013844	Thiazoles
D013457	Sulfur Compounds
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009025	Morpholines
D010078	Oxazines