Safety and Efficacy of a New Formulation of Bimatoprost/Timolol Ophthalmic Solution Compared With Bimatoprost/Timolol Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01177098
• Collaborator: (none)
• Enrollment: 561
• Locations: 9
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 62.3
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of bimatoprost/timolol formulation A ophthalmic solution with Ganfort® (bimatoprost 0.03%/timolol 0.5% ophthalmic solution) once daily for 12 weeks in patients with glaucoma or ocular hypertension.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma; Ocular Hypertension	Drug: bimatoprost /timolol formulation A fixed combination ophthalmic solution; Drug: bimatoprost/timolol fixed combination ophthalmic solution	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 561 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bimatoprost/timolol formulation A One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	Drug: bimatoprost /timolol formulation A fixed combination ophthalmic solution; One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.
Active Comparator: bimatoprost/timolol fixed combination ophthalmic solution One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.	Drug: bimatoprost/timolol fixed combination ophthalmic solution; One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.; Other Names: GANFORT®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Worse Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 12 [Baseline, Week 12]

   Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP was evaluated at Baseline and Week 12 at Hour 0, Hour 2 and Hour 8 in the worse eye, defined as the eye with the worse (higher) IOP at baseline. A negative number change from baseline indicates a reduction in IOP (improvement).

2. Average Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 2 [Week 2]

   Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP is the average IOP of both eyes and was evaluated at Week 2 at Hour 0, Hour 2 and Hour 8.

3. Average Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 6 [Week 6]

   Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP is the average IOP of both eyes and was evaluated at Week 6 at Hour 0, Hour 2 and Hour 8.

4. Average Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 12 [Week 12]

   Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP is the average IOP of both eyes and was evaluated at Week 12 at Hour 0, Hour 2 and Hour 8.

Secondary Outcome Measures

1. Change From Baseline in Worse Eye IOP at Each Hour Evaluated at Week 12 [Baseline, Week 12]

   Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP was evaluated at Baseline and Week 12 at Hour 0, Hour 2 and Hour 8 in the worse eye, defined as the eye with the worse (higher) IOP at baseline. A negative number change from baseline indicates a reduction in IOP (improvement).

2. Change From Baseline in Average Eye IOP at Each Hour Evaluated at Week 12 [Baseline, Week 12]

   Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP was evaluated at Baseline and Week 12 at Hour 0, Hour 2 and Hour 8. Average eye IOP is defined as the average of the IOP in both eyes. A negative number change from baseline indicates a reduction in IOP (improvement).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient has ocular hypertension or glaucoma in both eyes

• Requires IOP-lowering therapy in each eye

Exclusion Criteria:

• Active or recurrent eye disease that would interfere with interpretation of study data in either eye

• History of any eye surgery or laser in either eye within 6 months

• Required chronic use of other eye medications during the study

• Anticipated wearing of contact lenses during the study.

• Intermittent use of oral, intramuscular, or intravenous corticosteroids within 21 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Artesia	California	United States
2		Sydney	New South Wales	Australia
3		Brno		Czech Republic
4		Leipzig		Germany
5		Budapest		Hungary
6		Tel Aviv		Israel
7		Saint-Petersburg		Russian Federation
8		Valencia		Spain
9		London	England	United Kingdom

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01177098
• Other Study ID Numbers: 192024-050; 2010-021507-24
• First Posted: Aug 6, 2010
• Last Update Posted: Mar 29, 2013
• Last Verified: Mar 1, 2013

• Additional relevant MeSH terms: Glaucoma; Ocular Hypertension; Hypertension; Timolol; Bimatoprost; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Period Title: Overall Study
STARTED	278	283
COMPLETED	269	271
NOT COMPLETED	9	12

Baseline Characteristics

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution	Total
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.	Total of all reporting groups
Overall Participants	278	283	561
Age, Customized (Number) [Number]
<45 Years	12 (10.61) 4.3%	13 (10.82) 4.6%	25 (10.71) 4.5%
45 to 65 Years	132 47.5%	135 47.7%	267 47.6%
>65 Years	134 48.2%	135 47.7%	269 48%
Sex: Female, Male (Count of Participants)
Female	159 57.2%	162 57.2%	321 57.2%
Male	119 42.8%	121 42.8%	240 42.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Worse Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 12
Description	Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP was evaluated at Baseline and Week 12 at Hour 0, Hour 2 and Hour 8 in the worse eye, defined as the eye with the worse (higher) IOP at baseline. A negative number change from baseline indicates a reduction in IOP (improvement).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Per-protocol population included randomized participants who did not have a protocol violation that significantly affected the conduct or the results of the trial.

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Measure Participants	256	260
Baseline_Hour 0	25.41 (2.232)	25.38 (2.209)
Baseline_Hour 2 (n=255,260)	24.79 (2.676)	24.72 (2.470)
Baseline_Hour 8 (n=254,259)	23.88 (3.008)	23.82 (2.747)
Change from baseline at Week 12_Hour 0 (n=244,237)	-9.06 (3.216)	-8.72 (3.088)
Change from baseline at Week 12_Hour 2 (n=235,235)	-8.53 (3.520)	-8.38 (3.297)
Change from baseline at Week 12_Hour 8 (n=237,234)	-7.98 (3.435)	-7.72 (3.172)

2. Primary Outcome

Title	Average Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 2
Description	Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP is the average IOP of both eyes and was evaluated at Week 2 at Hour 0, Hour 2 and Hour 8.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants.

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Measure Participants	278	283
Week 2_Hour 0	16.23 (2.746)	16.49 (2.887)
Week 2_Hour 2	16.05 (2.877)	16.23 (2.826)
Week 2_Hour 8	15.49 (2.596)	15.83 (2.987)

3. Secondary Outcome

Title	Change From Baseline in Worse Eye IOP at Each Hour Evaluated at Week 12
Description	Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP was evaluated at Baseline and Week 12 at Hour 0, Hour 2 and Hour 8 in the worse eye, defined as the eye with the worse (higher) IOP at baseline. A negative number change from baseline indicates a reduction in IOP (improvement).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants.

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Measure Participants	278	283
Baseline_Hour 0	25.34 (2.233)	25.30 (2.244)
Baseline_Hour 2	24.71 (2.700)	24.61 (2.536)
Baseline_Hour 8	23.81 (2.989)	23.80 (2.795)
Change from baseline at Week 12_Hour 0	-8.94 (3.290)	-8.51 (3.253)
Change from baseline at Week 12_Hour 2	-8.44 (3.646)	-8.08 (3.504)
Change from baseline at Week 12_Hour 8	-7.87 (3.496)	-7.52 (3.362)

4. Secondary Outcome

Title	Change From Baseline in Average Eye IOP at Each Hour Evaluated at Week 12
Description	Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP was evaluated at Baseline and Week 12 at Hour 0, Hour 2 and Hour 8. Average eye IOP is defined as the average of the IOP in both eyes. A negative number change from baseline indicates a reduction in IOP (improvement).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants.

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Measure Participants	278	283
Baseline_Hour 0	24.94 (2.116)	24.86 (2.131)
Baseline_Hour 2	24.29 (2.515)	24.23 (2.426)
Baseline_Hour 8	23.42 (2.904)	23.36 (2.703)
Change from baseline at Week 12_Hour 0	-8.65 (3.109)	-8.30 (3.009)
Change from baseline at Week 12_Hour 2	-8.11 (3.392)	-7.86 (3.413)
Change from baseline at Week 12_Hour 8	-7.57 (3.395)	-7.27 (3.226)

5. Primary Outcome

Title	Average Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 6
Description	Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP is the average IOP of both eyes and was evaluated at Week 6 at Hour 0, Hour 2 and Hour 8.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants.

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Measure Participants	278	283
Week 6_Hour 0	16.28 (2.754)	16.31 (2.874)
Week 6_Hour 2	15.90 (2.910)	16.17 (2.894)
Week 6_Hour 8	15.71 (2.755)	15.82 (2.926)

6. Primary Outcome

Title	Average Eye Intraocular Pressure (IOP) at Each Hour Evaluated at Week 12
Description	Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. Average eye IOP is the average IOP of both eyes and was evaluated at Week 12 at Hour 0, Hour 2 and Hour 8.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants.

Arm/Group Title	Bimatoprost/Timolol Formulation A	Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.	One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Measure Participants	278	283
Week 12_Hour 0	16.29 (2.783)	16.56 (2.643)
Week 12_Hour 2	16.18 (2.845)	16.37 (2.699)
Week 12_Hour 8	15.85 (2.786)	16.09 (2.714)

Adverse Events

Adverse Event Reporting Description	The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Arm/Group Title	Bimatoprost/Timolol Formulation A		Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost/timolol formulation A fixed combination ophthalmic solution administered in each eye every morning for 12 weeks.		One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
All Cause Mortality
	Bimatoprost/Timolol Formulation A		Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bimatoprost/Timolol Formulation A		Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/278 (1.4%)		4/282 (1.4%)
General disorders
Non-cardiac chest pain	0/278 (0%)		1/282 (0.4%)
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	1/278 (0.4%)		0/282 (0%)
Osteoarthritis	1/278 (0.4%)		0/282 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	1/278 (0.4%)		0/282 (0%)
Lung neoplasm malignant	0/278 (0%)		1/282 (0.4%)
Non-Hodgkin's lymphoma	0/278 (0%)		1/282 (0.4%)
Nervous system disorders
Cerebellar infarction	0/278 (0%)		1/282 (0.4%)
Vascular disorders
Intermittent claudication	1/278 (0.4%)		0/282 (0%)
Other (Not Including Serious) Adverse Events
	Bimatoprost/Timolol Formulation A		Bimatoprost/Timolol Fixed Combination Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/278 (21.2%)		55/282 (19.5%)
Eye disorders
Conjunctival hyperaemia	59/278 (21.2%)		55/282 (19.5%)

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.