Efficacy and Safety Study of Bimatoprost Sustained-Release (SR) in Participants With Open-angle Glaucoma or Ocular Hypertension

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02247804
• Collaborator: (none)
• Enrollment: 594
• Locations: 106
• Arms: 3
• Actual Duration (Months): 55.1
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of bimatoprost SR in participants with open-angle glaucoma or ocular hypertension. The study includes a 12-month treatment period with an 8-month extended follow-up.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma, Open-Angle; Ocular Hypertension	Drug: Bimatoprost SR; Drug: Active Comparator: Timolol 0.5%; Other: Sham: Applicator Without Needle; Drug: Timolol Vehicle (placebo)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 594 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Efficacy and Safety of Bimatoprost SR in Patients With Open-angle Glaucoma or Ocular Hypertension
• Actual Study Start Date: Dec 15, 2014
• Actual Primary Completion Date: Feb 19, 2018
• Actual Study Completion Date: Jul 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Bimatoprost SR; Bimatoprost SR administered in the study eye on Day 1, Week 16, and Week 32.; Other Names: AGN-192024 ; Drug: Active Comparator: Timolol 0.5%; Timolol 0.5% administered once in the morning and once in the evening for up to 20 months.; Other: Sham: Applicator Without Needle; Sham administered on Day 1, Week 16, and Week 32.; Drug: Timolol Vehicle (placebo); Timolol vehicle administered once in the morning and once in the evening for up to 20 months.
Experimental: 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.	Drug: Bimatoprost SR; Bimatoprost SR administered in the study eye on Day 1, Week 16, and Week 32.; Other Names: AGN-192024 ; Drug: Active Comparator: Timolol 0.5%; Timolol 0.5% administered once in the morning and once in the evening for up to 20 months.; Other: Sham: Applicator Without Needle; Sham administered on Day 1, Week 16, and Week 32.; Drug: Timolol Vehicle (placebo); Timolol vehicle administered once in the morning and once in the evening for up to 20 months.
Active Comparator: Timolol 0.5% 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%; Timolol 0.5% administered once in the morning and once in the evening for up to 20 months.; Other: Sham: Applicator Without Needle; Sham administered on Day 1, Week 16, and Week 32.

Outcome Measures

Primary Outcome Measures

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

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

3. IOP in the Study Eye at Week 2 (Hour 2) [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.

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

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

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

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

Secondary Outcome Measures

1. Change From Baseline in IOP in the Study Eye [Baseline (Hours 0 and 2) to Weeks 2 and 6 (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. MMRM was used for analyses. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

-Diagnosis of either open-angle glaucoma or ocular hypertension in each eye and both eyes require IOP-lowering treatment.

Exclusion Criteria:

• Previous enrollment in another Allergan Bimatoprost SR Study.

• Eye surgery (including cataract surgery) and/or any eye laser surgery within the past 6 months in the study eye

• Anticipated need for laser eye surgery in either eye within the first 52 weeks of the study duration

• History of glaucoma surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Glaucoma Specialists	Phoenix	Arizona	United States	85050
2	Lugene Eye Institute	Glendale	California	United States	91205
3	Lakeside Vision Center	Irvine	California	United States	92604
4	Hamilton Glaucoma Center, Shiley Eye Center UCSD	La Jolla	California	United States	92037
5	Atlantis Eye Care	Long Beach	California	United States	90808
6	Glaucoma Institute of Beverly Hills	Los Angeles	California	United States	90048
7	Montebello Medical Eye Center Inc.	Montebello	California	United States	90640
8	Stanford University	Palo Alto	California	United States	94303
9	Foothill Eye Institute	Pasadena	California	United States	91107
10	Martel Eye Medical Group	Rancho Cordova	California	United States	95670
11	Grutzmacher, Lewis and Sierra, Inc.	Sacramento	California	United States	95815
12	Pacific Eye Associates	San Francisco	California	United States	94115
13	Eye Associates of Colorado Springs	Colorado Springs	Colorado	United States	80907
14	Palm Beach Eye Center, INC	Atlantis	Florida	United States	33461
15	Nature Coast Clinical Research	Crystal River	Florida	United States	34429
16	Levenson Eye Associates	Jacksonville	Florida	United States	32204
17	East Florida Eye Institute	Stuart	Florida	United States	34994
18	International Research Center	Tampa	Florida	United States	33603
19	Coastal Research Associates, LLC	Roswell	Georgia	United States	30076
20	Chicago Eye Specialists	Chicago	Illinois	United States	60619
21	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
22	Heart of America Eye Care PA	Shawnee Mission	Kansas	United States	66204
23	Tulane Medical Center	New Orleans	Louisiana	United States	70112
24	Eye Doctors of Washington	Chevy Chase	Maryland	United States	20815
25	MedRACS, LLC	Quincy	Massachusetts	United States	02169
26	Ocular Immunology and Uveitis Foundation	Waltham	Massachusetts	United States	02451
27	University of Michigan	Ann Arbor	Michigan	United States	48109
28	Minnesota Eye Constultants, P.A.	Bloomington	Minnesota	United States	55431
29	Lifelong Vision Foundation	Chesterfield	Missouri	United States	63017
30	Moyes Eye Center, PC	Kansas City	Missouri	United States	64154
31	Northern New Jersey Eye Institute P.A.	South Orange	New Jersey	United States	07079
32	Eyecare Ophthalmology Associates, PC	Bethpage	New York	United States	11714
33	Montefiore Medical Center	Bronx	New York	United States	10467
34	New York Eye and Ear Infirmary of Mount Sinai	New York	New York	United States	10003
35	Rochester Ophthalmological Group PC	Rochester	New York	United States	14618
36	2000 North Village Avenue	Rockville Centre	New York	United States	11570
37	Glaucoma Consultants of the Capital Region	Slingerlands	New York	United States	12159
38	8 Medical Park Drive	Asheville	North Carolina	United States	28803
39	Albemarle Clinical Trials, LLC	Elizabeth City	North Carolina	United States	27909
40	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
41	The Ohio State University Havener Eye Institute	Columbus	Ohio	United States	43212
42	Drs Fine Hoffman & Sims, LLC	Eugene	Oregon	United States	97401
43	Wills Eye Institute - Glaucoma Research Center	Philadelphia	Pennsylvania	United States	19107
44	Associates in Ophthalmology	Pittsburgh	Pennsylvania	United States	15219
45	Carolinas Centers for Sight PC	Florence	South Carolina	United States	29501
46	VRF Eye Specialty Group	Memphis	Tennessee	United States	38120
47	Nashville Vision Associates	Nashville	Tennessee	United States	37205
48	Keystone Research, LTD	Austin	Texas	United States	78731
49	Glaucoma Associates of Texas	Dallas	Texas	United States	75231
50	The Cataract, Glaucoma & Refractive Surgery Center	El Paso	Texas	United States	79902
51	Houston Eye Associates	Houston	Texas	United States	77025
52	Focal Point Vision	San Antonio	Texas	United States	78229
53	R and R Eye Research, LLC	San Antonio	Texas	United States	78234
54	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
55	Piedmont Eye Center	Lynchburg	Virginia	United States	24502
56	West Virginia University	Morgantown	West Virginia	United States	26506
57	Vision Eye Institute Chatswood	Chatsworth		Australia	New South Wales
58	Melbourne Eye Specialists	Fitzroy		Australia	Victoria 3065
59	Waverley Eye Clinic	Glen Waverley		Australia	Vctoria 3150
60	Marsden Eye Specialists, Parramatta	Paramatta		Australia	New South Wales
61	Preston Eye Clinic	Preston		Australia	Victoria 3072
62	University of Graz	Graz		Austria	A-8036
63	University of Vienna	Vienna		Austria	1090
64	University Hospitals Leuven	Leuven		Belgium	B-3000
65	CHU Sart Tilman	Liege		Belgium	4000
66	Universidade Federal de Goias	Goiania	Goias	Brazil	74180-010
67	Elo Oftalmologistas Associados	Belo Horizonte	Minas Gerais	Brazil	30140-090
68	Nova Campinas Oftalmologia	Campinas	Sao Paulo	Brazil	13010-111
69	Hospital Medicina dos Olhos	Osasco	Sao Paulo	Brazil	06010-130
70	Hospital de Olhos MS	Rio Verde		Brazil	79002-075
71	Escola Paulista de Medicina	Sao Paulo		Brazil	04023-062
72	Hospital das Clínicas - Faculdade de Medicina	Sao Paulo		Brazil	14049-900
73	Glostrup Hospital	Glostrup		Denmark	2600
74	Hong Kong Eye Hospital	Hong Kong		Hong Kong
75	The University of Hong Kong	Hong Kong		Hong Kong
76	Ganglion Medical Center	Pecs		Hungary	H-7621
77	Markusovszky Korhaz	Szombathely		Hungary	H-9700
78	Zala Megyei Kórház	Zalaegerszeg		Hungary	H-8900
79	Barzilai Medical Center	Ashkelon		Israel	78278
80	Bnai Zion M.C.	Haifa		Israel	31048
81	Rambam Medical Center	Haifa		Israel	31096
82	Carmel Medical Center	Haifa		Israel	34362
83	Centro Oftalmológico Mácula Diagnóstico y Tratamiento	Lima		Peru	Lima 27
84	Asian Eye Institute	Makati		Philippines	1200
85	Pacific Eyecare & Laser Institute	Makati		Philippines	1200
86	Makati Medical Center	Makati		Philippines	1229
87	Prywatna Klinika Okulistyczna OFTALMIKA	Bydgoszcz		Poland	85-631
88	Optimum Profesorskie Centrum Okulistyki	Gdansk		Poland	80-211
89	Public Clinical Hospital No. 1	Lublin		Poland	20-079
90	ZOZ OKO- TEST Poradnia Okulistyczna	Nowy Targ		Poland	34-400
91	Diagnostic and Microsurgery Center of the Eye LENS	Olsztyn		Poland	10-424
92	Retina Sp. z o.o	Warsaw		Poland	01-364
93	Klinika Okulistyki WIML	Warsaw		Poland	01-755
94	Uniwersytecki Szpital Kliniczny	Warszawa		Poland	01-755
95	Uniwersyteck Szpital Kliniczny	Wroclaw		Poland	50-368
96	Institut Clinic d'Oftalmologia	Barcelona		Spain	08006
97	Institut Catala de la Retina	Barcelona		Spain	08017
98	Hospital General de Catalunya	Barcelona		Spain	08195
99	Hospital Universitario Reina Sofía	Cordoba		Spain	14004
100	Hospital Clinico San Carlos	Madrid		Spain	28004
101	Hospital Universitario Virgen Macarena	Sevilla		Spain	41071
102	Hospital General	Valencia		Spain	46017
103	Hospital Universitario Rio Hortega	Valladolid		Spain	47012
104	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
105	Buddhist Tzu Chi General Hospital (BTCGH)	Hualien		Taiwan	970
106	Kaohsiung Veterans General Hospital	Kaohsiung		Taiwan	81362

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Marina Bejanian, Allergan

Study Documents (Full-Text)

• Statistical Analysis Plan - Apr 19, 2018
• Study Protocol - Mar 16, 2017

More Information

Additional Information:

• More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02247804
• Other Study ID Numbers: 192024-091; 2014-003037-26
• First Posted: Sep 25, 2014
• Last Update Posted: Jun 11, 2020
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol; Bimatoprost

Study Results

Participant Flow

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Period Title: Treatment Period 1
STARTED	198	198	198
Received (Sham or Bimatoprost SR)	193	197	197
COMPLETED	176	194	190
NOT COMPLETED	22	4	8
Period Title: Treatment Period 1
STARTED	172	191	187
COMPLETED	164	186	179
NOT COMPLETED	8	5	8
Period Title: Treatment Period 1
STARTED	158	183	177
COMPLETED	147	173	167
NOT COMPLETED	11	10	10

Baseline Characteristics

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	198	198	198	594
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (13.0)	62.6 (11.5)	62.5 (11.0)	62.5 (11.9)
Sex: Female, Male (Count of Participants)
Female	96 48.5%	86 43.4%	106 53.5%	288 48.5%
Male	102 51.5%	112 56.6%	92 46.5%	306 51.5%
Race/Ethnicity, Customized (Count of Participants)
White	122 61.6%	123 62.1%	130 65.7%	375 63.1%
Black or African American	30 15.2%	31 15.7%	21 10.6%	82 13.8%
Asian	12 6.1%	17 8.6%	16 8.1%	45 7.6%
Hispanic	27 13.6%	23 11.6%	25 12.6%	75 12.6%
Other	6 3%	4 2%	5 2.5%	15 2.5%
Not Reported	1 0.5%	0 0%	1 0.5%	2 0.3%
Intraocular Pressure (IOP) (mm Hg) [Mean (Full Range) ]
Hour 0	24.76	24.64	24.63	24.68
Hour 2	23.56	23.29	23.19	23.35

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in IOP in the Study Eye at Week 12 (Hours 0 and 2)
Description	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.
Time Frame	Baseline (Hours 0 and 2) to Week 12 (Hours 0 and 2)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	198	198	198
Change from Baseline at Hour 0, Week 12	-6.46 (0.29)	-6.38 (0.28)	-6.05 (0.28)
Change from Baseline at Hour 2, Week 12	-7.18 (0.26)	-6.69 (0.25)	-6.48 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	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).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.2950
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -1.17 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 12, Hour 0: The null hypothesis was that bimatoprost SR 10 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).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.3904
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -1.09 to 0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 12, Hour 2: 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).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0464
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 95%; -1.40 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 12, Hour 2: The null hypothesis was that bimatoprost SR 10 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).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.5383
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.90 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

2. Primary Outcome

Title	IOP in the Study Eye at Week 2 (Hour 0)
Description	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.
Time Frame	Week 2 (Hour 0)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	191	196	196
Least Squares Mean (Standard Error) [mm Hg]	16.82 (0.25)	17.02 (0.25)	17.83 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Week 2, 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -1.68 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Week 2, Hour 0: The null hypothesis was that bimatoprost SR 10 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0187
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.47 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

3. Primary Outcome

Title	IOP in the Study Eye at Week 2 (Hour 2)
Description	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.
Time Frame	Week 2 (Hour 2)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	191	196	196
Least Squares Mean (Standard Error) [mm Hg]	16.48 (0.22)	16.42 (0.22)	17.33 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Week 2, Hour 2: 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0057
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.85
	Confidence Interval	() 95%; -1.45 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Week 2, Hour 2: The null hypothesis was that bimatoprost SR 10 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.90
	Confidence Interval	() 95%; -1.50 to -0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.30
	Estimation Comments

4. Primary Outcome

Title	IOP in the Study Eye at Week 6 (Hour 0)
Description	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.
Time Frame	Week 6 (Hour 0)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	188	197	194
Least Squares Mean (Standard Error) [mm Hg]	17.08 (0.24)	16.88 (0.23)	17.71 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Week 6, 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0547
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.63
	Confidence Interval	() 95%; -1.26 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Week 6, Hour 0: The null hypothesis was that bimatoprost SR 10 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0107
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.82
	Confidence Interval	() 95%; -1.46 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

5. Primary Outcome

Title	IOP in the Study Eye at Week 6 (Hour 2)
Description	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.
Time Frame	Week 6 (Hour 2)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	187	197	193
Least Squares Mean (Standard Error) [mm Hg]	16.62 (0.23)	16.51 (0.22)	17.16 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Week 6, Hour 2: 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0860
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	0.08
	Confidence Interval	() 95%; -1.16 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Week 6, Hour 2: The null hypothesis was that bimatoprost SR 10 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0362
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.66
	Confidence Interval	() 95%; -1.27 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments

6. Primary Outcome

Title	IOP in the Study Eye at Week 12 (Hour 0)
Description	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.
Time Frame	Week 12 (Hour 0)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	185	192	191
Least Squares Mean (Standard Error) [mm Hg]	17.53 (0.29)	17.61 (0.28)	17.94 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.2950
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.41
	Confidence Interval	() 95%; -1.17 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Week 12, Hour 0: The null hypothesis was that bimatoprost SR 10 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.3904
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -1.09 to 0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments

7. Primary Outcome

Title	IOP in the Study Eye at Week 12 (Hour 2)
Description	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.
Time Frame	Week 12 (Hour 2)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	183	192	191
Least Squares Mean (Standard Error) [mm Hg]	16.81 (0.26)	17.30 (0.25)	17.51 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Week 12, Hour 2: 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0464
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.70
	Confidence Interval	() 95%; -1.40 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Week 12, Hour 2: The null hypothesis was that bimatoprost SR 10 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 Weeks 2, 6, 12).
	Type of Statistical Test	Non-Inferiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.5383
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.21
	Confidence Interval	() 95%; -0.90 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in IOP in the Study Eye
Description	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.
Time Frame	Baseline (Hours 0 and 2) to Weeks 2 and 6 (Hours 0 and 2)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bimatoprost SR 15 μg	Bimatoprost SR 10 μg	Timolol 0.5%: Comparator
Arm/Group Description	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.	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.	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.
Measure Participants	198	198	198
Change from Baseline at Hour 0, Week 2	-7.17 (0.25)	-6.97 (0.25)	-6.17 (0.25)
Change from Baseline at Hour 2, Week 2	-7.52 (0.22)	-7.57 (0.22)	-6.67 (0.22)
Change from Baseline at Hour 0, Week 6	-6.91 (0.24)	-7.11 (0.23)	-6.29 (0.24)
Change from Baseline at Hour 2, Week 6	-7.37 (0.23)	-7.48 (0.22)	-6.83 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 2, Hour 0: The null hypothesis was that bimatoprost SR 10 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -1.68 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 2, Hour 0: The null hypothesis was that bimatoprost SR 10 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0187
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.47 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 2, Hour 2: The null hypothesis was that bimatoprost SR 15 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0057
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95%; -1.45 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 2, Hour 2: The null hypothesis was that bimatoprost SR 10 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.90
	Confidence Interval	(2-Sided) 95%; -1.50 to -0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.30
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 6, Hour 0: The null hypothesis was that bimatoprost SR 15 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0547
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -1.26 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 6, Hour 0: The null hypothesis was that bimatoprost SR 10 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0107
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95%; -1.46 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 15 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 6, Hour 2: The null hypothesis was that bimatoprost SR 15 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0860
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -1.16 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost SR 10 μg, Timolol 0.5%: Comparator
	Comments	Change from Baseline Week 6, Hour 2: The null hypothesis was that bimatoprost SR 10 μg was to be declared superior to timolol 0.5% if the upper limit of the 95% CI was < 0 mm Hg for all scheduled timepoints (Hours 0 and 2 at Weeks 2, 6, 12).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0362
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least-squares Mean Difference
	Estimated Value	-0.66
	Confidence Interval	() 95%; -1.27 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments

Adverse Events

Time Frame	First dose of study drug to last visit (Up to approximately 20 months)
Adverse Event Reporting Description	Safety population included all participants who received at least 1 dose of study treatment.
Arm/Group Title	Bimatoprost SR 15 μg		Bimatoprost SR 10 μg		Timolol 0.5%: Comparator
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Bimatoprost SR 15 μg		Bimatoprost SR 10 μg		Timolol 0.5%: Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/193 (1%)		1/197 (0.5%)		1/197 (0.5%)
Serious Adverse Events
	Bimatoprost SR 15 μg		Bimatoprost SR 10 μg		Timolol 0.5%: Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/193 (16.1%)		25/197 (12.7%)		18/197 (9.1%)
Cardiac disorders
Acute myocardial infarction	2/193 (1%)		0/197 (0%)		0/197 (0%)
Acute coronary syndrome	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Cardiac arrest	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Myocardial infarction	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Atrial fibrillation	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Cardiac failure	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Bradycardia	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Eye disorders
Corneal endothelial cell loss	12/193 (6.2%)		4/197 (2%)		0/197 (0%)
Corneal oedema	3/193 (1.6%)		2/197 (1%)		0/197 (0%)
Iridocyclitis	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Corneal touch	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Macular oedema	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Retinal tear	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Ulcerative keratitis	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Uveitis	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Retinal detachment	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Gastrointestinal disorders
Haemorrhoids	1/193 (0.5%)		0/197 (0%)		1/197 (0.5%)
Small intestinal obstruction	1/193 (0.5%)		0/197 (0%)		1/197 (0.5%)
Gastric ulcer	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Intestinal obstruction	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Umbilical hernia	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Diarrhoea	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Abdominal pain	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Peptic ulcer	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Hiatus hernia	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
General disorders
Chest pain	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Infections and infestations
Clostridium difficile infection	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Appendicitis perforated	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Diverticulitis	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Gastroenteritis	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Post procedural sepsis	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Urinary tract infection	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Injury, poisoning and procedural complications
Femur fracture	1/193 (0.5%)		1/197 (0.5%)		1/197 (0.5%)
Road traffic accident	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Humerus fracture	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Radius fracture	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Fall	0/193 (0%)		0/197 (0%)		2/197 (1%)
Head injury	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Rib fracture	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Metabolism and nutrition disorders
Dehydration	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Lumbar spinal stenosis	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Osteoarthritis	0/193 (0%)		1/197 (0.5%)		1/197 (0.5%)
Intervertebral disc protrusion	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Joint instability	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal proliferative breast lesion	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Basal cell carcinoma	0/193 (0%)		2/197 (1%)		0/197 (0%)
Prostate cancer	0/193 (0%)		1/197 (0.5%)		1/197 (0.5%)
Squamous cell carcinoma	0/193 (0%)		1/197 (0.5%)		1/197 (0.5%)
Malignant melanoma	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Parathyroid tumour benign	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Hepatocellular carcinoma	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Invasive breast carcinoma	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Meningioma	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Prostate cancer recurrent	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Nervous system disorders
Cerebrovascular accident	1/193 (0.5%)		0/197 (0%)		2/197 (1%)
Cerebral haemorrhage	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Embolic stroke	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Headache	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Trigeminal neuralgia	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Sciatica	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
VIth nerve paralysis	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Renal and urinary disorders
Renal failure	1/193 (0.5%)		1/197 (0.5%)		0/197 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/193 (0.5%)		1/197 (0.5%)		1/197 (0.5%)
Acute pulmonary oedema	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Chronic obstructive pulmonary disease	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Pneumothorax spontaneous	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Pulmonary hypertension	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Vascular disorders
Internal haemorrhage	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Varicose vein	1/193 (0.5%)		0/197 (0%)		0/197 (0%)
Deep vein thrombosis	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Hypotension	0/193 (0%)		1/197 (0.5%)		0/197 (0%)
Peripheral arterial occlusive disease	0/193 (0%)		0/197 (0%)		1/197 (0.5%)
Other (Not Including Serious) Adverse Events
	Bimatoprost SR 15 μg		Bimatoprost SR 10 μg		Timolol 0.5%: Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	143/193 (74.1%)		138/197 (70.1%)		105/197 (53.3%)
Eye disorders
Conjunctival hyperaemia	74/193 (38.3%)		60/197 (30.5%)		47/197 (23.9%)
Foreign body sensation in eyes	31/193 (16.1%)		23/197 (11.7%)		12/197 (6.1%)
Eye pain	28/193 (14.5%)		26/197 (13.2%)		12/197 (6.1%)
Eye irritation	28/193 (14.5%)		18/197 (9.1%)		22/197 (11.2%)
Photophobia	23/193 (11.9%)		19/197 (9.6%)		4/197 (2%)
Corneal endothelial cell loss	20/193 (10.4%)		14/197 (7.1%)		0/197 (0%)
Conjunctival haemorrhage	19/193 (9.8%)		17/197 (8.6%)		16/197 (8.1%)
Iritis	19/193 (9.8%)		11/197 (5.6%)		1/197 (0.5%)
Dry eye	17/193 (8.8%)		19/197 (9.6%)		12/197 (6.1%)
Punctate keratitis	16/193 (8.3%)		12/197 (6.1%)		14/197 (7.1%)
Lacrimation increased	13/193 (6.7%)		10/197 (5.1%)		12/197 (6.1%)
Vision blurred	12/193 (6.2%)		10/197 (5.1%)		11/197 (5.6%)
Corneal oedema	12/193 (6.2%)		5/197 (2.5%)		2/197 (1%)
Anterior chamber cell	11/193 (5.7%)		9/197 (4.6%)		0/197 (0%)
Infections and infestations
Nasopharyngitis	13/193 (6.7%)		10/197 (5.1%)		14/197 (7.1%)
Influenza	8/193 (4.1%)		13/197 (6.6%)		4/197 (2%)
Investigations
Intraocular pressure increased	13/193 (6.7%)		20/197 (10.2%)		7/197 (3.6%)
Nervous system disorders
Headache	8/193 (4.1%)		14/197 (7.1%)		7/197 (3.6%)
Visual field defect	4/193 (2.1%)		10/197 (5.1%)		5/197 (2.5%)
Vascular disorders
Hypertension	17/193 (8.8%)		12/197 (6.1%)		8/197 (4.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.