Efficacy and Safety of Bimatoprost Sustained-Release (SR)... | NCT02250651

NCT02250651

ID	Type	Description	Link
2014-003186-24	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 micrograms (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 Other: Sham: Applicator Without Needle Drug: Active Comparator: Timolol 0.5% 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 Other: Sham: Applicator Without Needle Drug: Active Comparator: Timolol 0.5% Drug: Timolol Vehicle (placebo)
Timolol 0.5%: Comparator	Active Comparator	Both Eyes: 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.	Other: Sham: Applicator Without Needle Drug: Active Comparator: Timolol 0.5%

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 Intraocular Pressure (IOP) in the Study Eye to 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 (Up to 3 days prior to Day 1 at 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
Margot Goodkin	Allergan	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Eye Center South		Dothan	Alabama	36301	United States
Arizona Eye Center

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 micrograms (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
Prot	Yes	No	No	Study Protocol	Jun 5, 2018	Apr 29, 2021

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
	ParticipantsBG000176 ParticipantsBG001176 ParticipantsBG002176 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000176 ParticipantsBG001176 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000176 ParticipantsBG001176 ParticipantsBG002

Intraocular Pressure (IOP)

The number analyzed is the number of participants with data available for IOP at Baseline.

Mean

Full Range

millimeters of mercury (mmHg)

Title	Denominators	Categories
Hour 0	ParticipantsBG000176 ParticipantsBG001

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 Intraocular Pressure (IOP) in the Study Eye to 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.

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

millimeters of mercury (mmHg)

Baseline (Up to 3 days prior to Day 1 at 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	OG000176 OG001176 OG002176

Title

Denominators

Categories

Change from Baseline at Week 12, Hour 0

- ParticipantsOG000168
- ParticipantsOG001169
- ParticipantsOG002165

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 at Week 12, Hour 0: The 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 mmHg for all scheduled timepoints (Hours 0 and 2 at Week 12).	MMRM		0.3738		Least-squares Mean Difference	-0.36	Standard Error of the Mean	0.41	2-Sided	95	-1.17	0.44					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)

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

mmHg

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)

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

mmHg

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)

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

mmHg

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)

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

mmHg

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)

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

mmHg

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)

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

mmHg

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.

Participants from the ITT Population, all randomized participants, with data available for analyses.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline (Up to 3 days prior to Day 1 at 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.	1	176	36	176	133	176
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.	0	176	22	175	103	175
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	176	16	173	72	173

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Angina pectoris	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Angina unstable	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Coronary artery disease	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Sudden hearing loss	Ear and labyrinth disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Ascites	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0022 affected173 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Nausea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Death	General disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Sarcoidosis	Immune system disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Pneumonia	Infections and infestations	MedDRA 22.0	Systematic Assessment		EG0003 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Appendicitis	Infections and infestations	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Jaw fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0012 affected175 at risk EG0020 affected173 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0021 affected173 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment		EG0003 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	Number of participants at risk are male participants as this adverse event is specific to males.	EG0002 affected85 at risk EG0010 affected85 at risk EG0021 affected88 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0002 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Breast cancer stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Natural killer-cell leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Waldenstrom's macroglobulinaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Bronchial carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Oropharyngeal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Follicular thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Small intestine carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Encephalopathy	Nervous system disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0012 affected175 at risk EG0020 affected173 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Bipolar disorder	Psychiatric disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Depression	Psychiatric disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Schizophrenia	Psychiatric disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
End stage renal disease	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA 22.0	Systematic Assessment	Number of participants at risk are female participants as this adverse event is specific to females.	EG0000 affected91 at risk EG0011 affected90 at risk EG0020 affected85 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 22.0	Systematic Assessment	Number of participants at risk are female participants as this adverse event is specific to females.	EG0000 affected91 at risk EG0011 affected90 at risk EG0020 affected85 at risk
Aortic stenosis	Vascular disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Penetrating aortic ulcer	Vascular disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 22.0	Systematic Assessment		EG0000 affected176 at risk EG0010 affected175 at risk EG0021 affected173 at risk
Corneal endothelial cell loss	Eye disorders	MedDRA 22.0	Systematic Assessment	12 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=9, Bimatoprost SR 10 ug=3).	EG0009 affected176 at risk EG0013 affected175 at risk EG0020 affected173 at risk
Corneal oedema	Eye disorders	MedDRA 22.0	Systematic Assessment	3 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=2, Bimatoprost SR 10 ug=1).	EG0002 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Macular oedema	Eye disorders	MedDRA 22.0	Systematic Assessment	1 adverse event occurred in the study eye.	EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Product administered at inappropriate site	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Pterygium	Eye disorders	MedDRA 22.0	Systematic Assessment	1 adverse event occurred in the study eye.	EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
VIth nerve paralysis	Nervous system disorders	MedDRA 22.0	Systematic Assessment		EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk
Corneal decompensation	Eye disorders	MedDRA 22.0	Systematic Assessment	1 adverse event occurred in the study eye.	EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Retinal detachment	Eye disorders	MedDRA 22.0	Systematic Assessment	1 adverse event occurred in the study eye.	EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Visual impairment	Eye disorders	MedDRA 22.0	Systematic Assessment	1 adverse event occurred in the study eye.	EG0000 affected176 at risk EG0011 affected175 at risk EG0020 affected173 at risk
Retinal tear	Eye disorders	MedDRA 22.0	Systematic Assessment	1 adverse event occurred in the fellow (non-study) eye.	EG0001 affected176 at risk EG0010 affected175 at risk EG0020 affected173 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Conjunctival hyperaemia	Eye disorders	MedDRA 22.0	Systematic Assessment	138 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=71, Bimatoprost SR 10 ug=48, and Timolol 0.5%=19); 86 adverse events occurred in the fellow (non-study) eye.	EG00073 affected176 at risk EG00148 affected175 at risk EG00220 affected173 at risk
Corneal endothelial cell loss	Eye disorders	MedDRA 22.0	Systematic Assessment	50 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=38, Bimatoprost SR 10 ug=11, and Timolol 0.5%=1); 4 adverse events occurred in the fellow (non-study) eye.	EG00038 affected176 at risk EG00112 affected175 at risk EG0022 affected173 at risk
Eye pain	Eye disorders	MedDRA 22.0	Systematic Assessment	40 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=21, Bimatoprost SR 10 ug=11, and Timolol 0.5%=8); 16 adverse events occurred in the fellow (non-study) eye.	EG00023 affected176 at risk EG00112 affected175 at risk EG0029 affected173 at risk
Corneal oedema	Eye disorders	MedDRA 22.0	Systematic Assessment	26 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=21, Bimatoprost SR 10 ug=5).	EG00021 affected176 at risk EG0015 affected175 at risk EG0020 affected173 at risk
Foreign body sensation in eyes	Eye disorders	MedDRA 22.0	Systematic Assessment	37 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=18, Bimatoprost SR 10 ug=17, and Timolol 0.5%=2); 17 adverse events occurred in the fellow (non-study) eye.	EG00019 affected176 at risk EG00118 affected175 at risk EG0022 affected173 at risk
Dry eye	Eye disorders	MedDRA 22.0	Systematic Assessment	33 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=16, Bimatoprost SR 10 ug=10, and Timolol 0.5%=7); 31 adverse events occurred in the fellow (non-study) eye.	EG00018 affected176 at risk EG00112 affected175 at risk EG0027 affected173 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 22.0	Systematic Assessment	42 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=14, Bimatoprost SR 10 ug=16, and Timolol 0.5%=12); 22 adverse events occurred in the fellow (non-study) eye.	EG00017 affected176 at risk EG00120 affected175 at risk EG00215 affected173 at risk
Punctate keratitis	Eye disorders	MedDRA 22.0	Systematic Assessment	28 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=13, Bimatoprost SR 10 ug=8, and Timolol 0.5%=7); 26 adverse events occurred in the fellow (non-study) eye.	EG00014 affected176 at risk EG00110 affected175 at risk EG0028 affected173 at risk
Photophobia	Eye disorders	MedDRA 22.0	Systematic Assessment	26 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=13, Bimatoprost SR 10 ug=13); 13 adverse events occurred in the fellow (non-study) eye.	EG00013 affected176 at risk EG00113 affected175 at risk EG0020 affected173 at risk
Eye irritation	Eye disorders	MedDRA 22.0	Systematic Assessment	28 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=12, Bimatoprost SR 10 ug=9, and Timolol 0.5%=7); 23 adverse events occurred in the fellow (non-study) eye.	EG00013 affected176 at risk EG00110 affected175 at risk EG0029 affected173 at risk
Anterior chamber cell	Eye disorders	MedDRA 22.0	Systematic Assessment	19 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=12, Bimatoprost SR 10 ug=6, and Timolol 0.5%=1); 1 adverse event occurred in the fellow (non-study) eye.	EG00013 affected176 at risk EG0016 affected175 at risk EG0021 affected173 at risk
Ocular discomfort	Eye disorders	MedDRA 22.0	Systematic Assessment	15 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=11, Bimatoprost SR 10 ug=3, and Timolol 0.5%=1); 4 adverse events occurred in the fellow (non-study) eye.	EG00011 affected176 at risk EG0013 affected175 at risk EG0021 affected173 at risk
Iritis	Eye disorders	MedDRA 22.0	Systematic Assessment	17 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=9, Bimatoprost SR 10 ug=8); 1 adverse event occurred in the fellow (non-study) eye.	EG0009 affected176 at risk EG0018 affected175 at risk EG0020 affected173 at risk
Lacrimation increased	Eye disorders	MedDRA 22.0	Systematic Assessment	16 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=9, Bimatoprost SR 10 ug=6, and Timolol 0.5%=1); 12 adverse events occurred in the fellow (non-study) eye.	EG0009 affected176 at risk EG0017 affected175 at risk EG0021 affected173 at risk
Vision blurred	Eye disorders	MedDRA 22.0	Systematic Assessment	17 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=7, Bimatoprost SR 10 ug=9, and Timolol 0.5%=1); 11 adverse events occurred in the fellow (non-study) eye.	EG0007 affected176 at risk EG00111 affected175 at risk EG0021 affected173 at risk
Blepharitis	Eye disorders	MedDRA 22.0	Systematic Assessment	21 adverse events occurred in the study eye: (Bimatoprost SR 15 ug=7, Bimatoprost SR 10 ug=9, and Timolol 0.5%=5); 18 adverse events occurred in the fellow (non-study) eye.	EG0007 affected176 at risk EG00110 affected175 at risk EG0025 affected173 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment		EG0009 affected176 at risk EG00112 affected175 at risk EG00214 affected173 at risk
Intraocular pressure increased	Investigations	MedDRA 22.0	Systematic Assessment		EG00017 affected176 at risk EG00115 affected175 at risk EG0026 affected173 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