Bimatoprost Ocular Insert Compared to Topical Timolol Solution in Patients With Glaucoma or Ocular Hypertension

• Sponsor: ForSight Vision5, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01915940
• Collaborator: (none)
• Enrollment: 169
• Locations: 10
• Arms: 2
• Actual Duration (Months): 12.7
• Patients Per Site: 16.9
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The objective of this Phase 2 study is to evaluate whether the Bimatoprost Ocular Insert is non-inferior to that of timolol ophthalmic solution (0.5%) at 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Primary Open-Angle Glaucoma; Ocular Hypertension	Drug: Bimatoprost; Drug: Timolol 0.5%; Drug: Placebo Eye Drops; Device: Placebo Ocular Insert	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 169 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Subject- and Examiner-masked, Controlled Clinical Trial Designed to Evaluate the Safety and Effectiveness of the Bimatoprost Ocular Insert as Compared to Topical Timolol Solution (0.5%) in Patients With Glaucoma or Ocular Hypertension.
• Actual Study Start Date: Oct 23, 2013
• Actual Primary Completion Date: Sep 30, 2014
• Actual Study Completion Date: Nov 14, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 13 mg Bimatoprost Ocular Insert Washout and placebo ocular insert in each eye for at least 4 weeks, followed by 13 mg Bimatoprost Ocular Insert in each eye and placebo eye drops twice a day in each eye for 6 months.	Drug: Bimatoprost; Bimatoprost ocular insert; Drug: Placebo Eye Drops; Placebo topical eye drops; Device: Placebo Ocular Insert; Ocular insert without any active drug; Other Names: non-medicated (placebo) Ocular Insert
Active Comparator: Timolol 0.5% + Placebo Ocular Insert Washout and placebo ocular insert in each eye for at least 4 weeks, followed by Timolol (timoptic ophthalmic solution 0.5%) twice a day in each eye plus placebo ocular insert for 6 months.	Drug: Timolol 0.5%; Timolol 0.5% solution; Other Names: timoptic ; Device: Placebo Ocular Insert; Ocular insert without any active drug; Other Names: non-medicated (placebo) Ocular Insert

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Intra-Ocular Pressure (IOP) at Week 2 [Baseline (Day 0) to Week 2]

   IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (time (T)=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 2. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.

2. Change From Baseline in Intra-Ocular Pressure (IOP) at Week 6 [Baseline (Day 0) to Week 6]

   IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 6. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.

3. Change From Baseline in Intra-Ocular Pressure (IOP) at Week 12 [Baseline (Day 0) to Week 12]

   IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 12. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.

Secondary Outcome Measures

1. Change From Baseline in IOP at Month 4 [Baseline (Day 1) to Month 4]

   IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Month 4. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.

2. Change From Baseline in IOP at Month 5 [Baseline (Day 0) to Month 5]

   IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Month 5. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.

3. Change From Baseline in IOP at Month 6 [Baseline (Day 0) to Month 6]

   IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Month 6. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Written informed consent

• Primary open-angle glaucoma or ocular hypertension in both eyes

• Best-corrected distance vision of 20/80 or better

• Stable visual field

• corneal thickness between 490-620 micrometers

Key Exclusion Criteria:

• Cup-to-disc ratio greater than 0.8

• significant risk of angle closure due to pupil dilation, defined as a Shaffer classification of less than grade 2 based on gonioscopy

• laser surgery for glaucoma/ocular hypertension on one or both eyes within the last 12 months

• past history of corneal refractive surgery

• past history of any incisional surgery for glaucoma at any time

• corneal abnormalities that would interfere with tonometry readings

• current participation in an investigational drug or device study or participation in such a study within 30 days of screening

• Inability to accurately evaluate the retina

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sall Medical Research Center	Artesia	California	United States	90701
2	Scripps Clinic Torrey Pines	La Jolla	California	United States	92037
3	Eye Research Foundation	Newport Beach	California	United States	92663
4	UC Davis Dept of Ophthalmology & Vision Science	Sacramento	California	United States	95817
5	Coastal Research Associates	Atlanta	Georgia	United States	30076
6	Clayton Eye Center	Morrow	Georgia	United States	30260
7	Ophthalmology Consultants	Saint Louis	Missouri	United States	63131
8	UNC Kittner Eye Center	Chapel Hill	North Carolina	United States	27517
9	Apex Eye	Madeira	Ohio	United States	45243
10	Ophthalmology Associates PC	Fort Worth	Texas	United States	76102

Sponsors and Collaborators

• ForSight Vision5, Inc.

Investigators

• Study Director: Michelle Chen, PhD, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ForSight Vision5, Inc.
• ClinicalTrials.gov Identifier: NCT01915940
• Other Study ID Numbers: FSV5-002
• First Posted: Aug 5, 2013
• Last Update Posted: Apr 20, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by ForSight Vision5, Inc.: Glaucoma; Primary Open-Angle Glaucoma; Ocular Hypertension
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol; Bimatoprost; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	Washout + Placebo Ocular Insert	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Glaucoma medication washout and placebo ocular insert in each eye for at least 4 weeks.	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
Period Title: Pre-randomization Washout Period
STARTED	169	0	0
COMPLETED	130	0	0
NOT COMPLETED	39	0	0
Period Title: Pre-randomization Washout Period
STARTED	0	64	66
COMPLETED	0	53	62
NOT COMPLETED	0	11	4

Baseline Characteristics

Arm/Group Title	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert	Total
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.	Total of all reporting groups
Overall Participants	64	66	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (10.1)	66.3 (8.5)	65.6 (9.4)
Sex: Female, Male (Count of Participants)
Female	33 51.6%	44 66.7%	77 59.2%
Male	31 48.4%	22 33.3%	53 40.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Intra-Ocular Pressure (IOP) at Week 2
Description	IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (time (T)=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 2. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) to Week 2

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS), all randomized participants who had ocular inserts placed in their eye and who had at least 1 on-treatment study visit completed, with data available for analysis at the given time-point.

Arm/Group Title	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
Measure Participants	63	64
Baseline (T=0 hour)	24.99 (0.29)	25.34 (0.29)
Baseline (T=2 hour)	23.65 (0.31)	23.75 (0.28)
Baseline (T=8 hour)	22.95 (0.29)	23.16 (0.29)
Change from Baseline to Week 2 (T=0 hour)	-6.40 (0.41)	-6.30 (0.41)
Change from Baseline to Week 2 (T=2 hour)	-5.20 (0.34)	-5.59 (0.41)
Change from Baseline to Week 2 (T=8 hour)	-4.21 (0.35)	-4.96 (0.37)

2. Primary Outcome

Title	Change From Baseline in Intra-Ocular Pressure (IOP) at Week 6
Description	IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 6. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) to Week 6

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS), all randomized participants who had ocular inserts placed in their eye and who had at least 1 on-treatment study visit completed, with data available for analysis at the given time-point.

Arm/Group Title	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
Measure Participants	63	64
Baseline (T=0 hour)	24.99 (0.29)	25.34 (0.29)
Baseline (T=2 hour)	23.65 (0.31)	23.75 (0.28)
Baseline (T=8 hour)	22.95 (0.29)	23.16 (0.29)
Change from Baseline to Week 6 (T=0 hour)	-5.47 (0.40)	-6.41 (0.41)
Change from Baseline to Week 6 (T=2 hour)	-4.70 (0.31)	-5.40 (0.39)
Change from Baseline to Week 6 (T=8 hour)	-3.78 (0.34)	-4.42 (0.39)

3. Primary Outcome

Title	Change From Baseline in Intra-Ocular Pressure (IOP) at Week 12
Description	IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 12. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) to Week 12

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS), all randomized participants who had ocular inserts placed in their eye and who had at least 1 on-treatment study visit completed, with data available for analysis at the given time-point.

Arm/Group Title	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
Measure Participants	63	64
Baseline (T=0 hour)	24.99 (0.29)	25.34 (0.29)
Baseline (T=2 hour)	23.65 (0.31)	23.75 (0.28)
Baseline (T=8 hour)	22.95 (0.29)	23.16 (0.29)
Change from Baseline to Week 12 (T=0 hour)	-5.26 (0.47)	-6.31 (0.43)
Change from Baseline to Week 12 (T=2 hour)	-4.26 (0.44)	-5.60 (0.43)
Change from Baseline to Week 12 (T=8 hour)	-3.99 (0.33)	-5.19 (0.35)

4. Secondary Outcome

Title	Change From Baseline in IOP at Month 4
Description	IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Month 4. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.
Time Frame	Baseline (Day 1) to Month 4

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS), all randomized participants who had ocular inserts placed in their eye and who had at least 1 on-treatment study visit completed, with data available for analysis at the given time-point.

Arm/Group Title	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
Measure Participants	63	64
Baseline (T=0 hour)	24.99 (0.29)	25.34 (0.29)
Baseline (T=2 hour)	23.65 (0.31)	23.75 (0.28)
Baseline (T=8 hour)	22.95 (0.29)	23.16 (0.29)
Change from Baseline to Month 4 (T=0 hour)	-5.14 (0.43)	-6.29 (0.40)
Change from Baseline to Month 4 (T=2 hour)	-4.37 (0.38)	-5.26 (0.41)
Change from Baseline to Month 4 (T=8 hour)	-3.84 (0.34)	-5.11 (0.36)

5. Secondary Outcome

Title	Change From Baseline in IOP at Month 5
Description	IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Month 5. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) to Month 5

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS), all randomized participants who had ocular inserts placed in their eye and who had at least 1 on-treatment study visit completed, with data available for analysis at the given time-point.

Arm/Group Title	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
Measure Participants	63	64
Baseline (T=0 hour)	24.99 (0.29)	25.34 (0.29)
Baseline (T= 2 hour)	23.65 (0.31)	23.75 (0.28)
Baseline (T=8 hour)	22.95 (0.29)	23.16 (0.29)
Change from Baseline to Month 5 (T=0 hour)	-4.28 (0.36)	-6.35 (0.41)
Change from Baseline to Month 5 (T=2 hour)	-3.87 (0.39)	-5.45 (0.43)
Change from Baseline to Month 5 (T=8 hour)	-3.21 (0.34)	-4.47 (0.38)

6. Secondary Outcome

Title	Change From Baseline in IOP at Month 6
Description	IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Month 6. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) to Month 6

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS), all randomized participants who had ocular inserts placed in their eye and who had at least 1 on-treatment study visit completed, with data available for analysis at the given time-point.

Arm/Group Title	13 mg Bimatoprost Ocular Insert	Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.	Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
Measure Participants	63	64
Baseline (T=0 hour)	24.99 (0.29)	25.34 (0.29)
Baseline (T=2 hour)	23.65 (0.31)	23.75 (0.28)
Baseline (T=8 hour)	22.95 (0.29)	23.16 (0.29)
Change from Baseline to Month 6 (T=0 hour)	-4.58 (0.39)	-5.97 (0.42)
Change from Baseline to Month 6 (T=2 hour)	-3.87 (0.42)	-5.20 (0.41)
Change from Baseline to Month 6 (T=8 hour)	-3.25 (0.32)	-4.24 (0.37)

Adverse Events

Time Frame	Randomization (Day 0) to the end of study (Up to 6 Months)
Arm/Group Title	13 mg Bimatoprost Ocular Insert		Timolol 0.5% + Placebo Ocular Insert
Arm/Group Description	Following the washout period, 13 mg Bimatoprost Ocular Insert and placebo eye drops twice a day in each eye for 6 months.		Following the washout period, timolol ophthalmic solution 0.5% twice a day plus placebo ocular insert in each eye for 6 months.
All Cause Mortality
	13 mg Bimatoprost Ocular Insert		Timolol 0.5% + Placebo Ocular Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	13 mg Bimatoprost Ocular Insert		Timolol 0.5% + Placebo Ocular Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/64 (1.6%)		2/66 (3%)
Cardiac disorders
Atrial fibrillation	0/64 (0%)		1/66 (1.5%)
Immune system disorders
Drug hypersensitivity	0/64 (0%)		1/66 (1.5%)
Vascular disorders
Hypertension	1/64 (1.6%)		0/66 (0%)
Other (Not Including Serious) Adverse Events
	13 mg Bimatoprost Ocular Insert		Timolol 0.5% + Placebo Ocular Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/64 (31.3%)		14/66 (21.2%)
Eye disorders
Eye discharge	7/64 (10.9%)		7/66 (10.6%)
Conjunctival hyperaemia	9/64 (14.1%)		2/66 (3%)
Punctate keratitis	5/64 (7.8%)		4/66 (6.1%)
Eye pruritus	4/64 (6.3%)		1/66 (1.5%)
Infections and infestations
Upper respiratory tract infection	3/64 (4.7%)		5/66 (7.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

No presentation or publication of Institution's data relating to the Trial may occur until after the Trial has been completed at all sites. If Investigator desires to present or publish, investigator must submit any and all manuscripts, posters, abstracts, or other intended publications (hereinafter collectively referred to as "manuscripts") to Sponsor at least sixty (60) days prior to the actual submission of such manuscript(s) for publication.