Patient Satisfaction With Timolol in Subjects With Open-Angle Glaucoma or Ocular Hypertension

• Sponsor: Vistakon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00804648
• Collaborator: (none)
• Enrollment: 30
• Locations: 2
• Arms: 6
• Duration (Days): 30
• Patients Per Site: 15
• Patients Per Site Per Month: 15.2

Study Details

Study Description

Brief Summary

This study compares patient symptoms and anterior segment safety in patients treated with timolol hemihydrate, generic timolol gel forming solution or timolol maleate.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma, Open Angle; Ocular Hypertension	Drug: Timolol Maleate in Sorbate; Drug: Timolol hemihydrate; Drug: Timolol maleate gel forming solution	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Patient Satisfaction With Timolol Maleate in Sorbate, Generic Timolol Gel Forming Solution or Timolol Hemihydrate in Subjects With Open-Angle Glaucoma or Ocular Hypertension
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: hemihydrate/maleate/maleate gel Period one - Timolol hemihydrate 0.5% Period two - Timolol maleate 0.5% Period three - Timolol maleate gel forming solution 0.5%	Drug: Timolol Maleate in Sorbate; 0.5%; Drug: Timolol hemihydrate; 0.5%; Drug: Timolol maleate gel forming solution; 0.5%
Active Comparator: maleate/maleate gel/hemihydrate Period one - Timolol maleate 0.5% Period two - Timolol maleate gel forming solution 0.5% Period three - Timolol hemihydrate 0.5%	Drug: Timolol Maleate in Sorbate; 0.5%; Drug: Timolol hemihydrate; 0.5%; Drug: Timolol maleate gel forming solution; 0.5%
Active Comparator: maleate gel/hemihydrate/maleate Period one - Timolol maleate gel forming solution 0.5% Period two - Timolol hemihydrate 0.5% Period three - Timolol maleate 0.5%	Drug: Timolol Maleate in Sorbate; 0.5%; Drug: Timolol hemihydrate; 0.5%; Drug: Timolol maleate gel forming solution; 0.5%
Active Comparator: hemihydrate/maleate gel/maleate Period one - Timolol hemihydrate 0.5% Period two - Timolol maleate gel forming solution 0.5% Period three - Timolol maleate 0.5%	Drug: Timolol Maleate in Sorbate; 0.5%; Drug: Timolol hemihydrate; 0.5%; Drug: Timolol maleate gel forming solution; 0.5%
Active Comparator: maleate/hemihydrate/maleate gel Period 1 - Timolol maleate 0.5% Period 2 - Timolol hemihydrate 0.5% Period 3 - Timolol maleate gel forming solution 0.5%	Drug: Timolol Maleate in Sorbate; 0.5%; Drug: Timolol hemihydrate; 0.5%; Drug: Timolol maleate gel forming solution; 0.5%
Active Comparator: maleate gel, maleate, hemihydrate Period 1 - Timolol maleate gel forming solution 0.5% Period 2 - Timolol maleate 0.5% Period 3 - Timolol hemihydrate 0.5%	Drug: Timolol Maleate in Sorbate; 0.5%; Drug: Timolol hemihydrate; 0.5%; Drug: Timolol maleate gel forming solution; 0.5%

Outcome Measures

Primary Outcome Measures

1. Stinging on Instillation [following 3 days of treatment]

   Assessed from subject response to survey question asking about tolerability of medicine upon instillation, using a 0 through 7 scale, with 0=complete comfort and 7=worst pain imaginable.

Secondary Outcome Measures

1. Conjunctival Hyperemia [following 3 days of treatment]

   Assessed by investigator using a slit lamp and a photographic grading scale. Photographs were graded: grade 0, grade 1, grade 2, grade 3. The higher the graded the worse the hyperemia.

2. Tear Film Break-up Time [following 3 days of treatment]

3. Corneal Staining Grade [following 3 days of treatment]

   Assessed by the investigator using a slit lamp and Oxford Scheme, grading 0,1,2,3,4,5. The higher the grade the worse the staining.

4. Corneal Staining Count [following 3 days of treatment]

   Assessed by the investigator using a slit lamp, counting the number of spots.

5. Intraoclular Pressure [following 3 days of treatment]

6. Basic Schirmer's [following 3 days of treatment]

   Schirmer's measures basic tear function. The higher the number, the less dry the eye.

7. Conjunctival Staining - Nasal Grade [following 3 days of treatment]

   Assessed by investigator using a slit lamp and the Oxford Scheme, grading 0,1,2,3,4,5 according to pictures provided. The higher the grade the worse the staining.

8. Conjunctival Staining - Nasal Count [following 3 days of treatment]

   Assessed by investigator using slit lamp and counting number of spots.

9. Conjunctival Staining - Temporal Grade [following 3 days of treatment]

   Assessed by investigator using a slit lamp and Oxford Scheme, grading 0,1,2,3,4,5 according to pictures provided. The higher the grade the worse the staining.

10. Conjunctival Staining - Temporal Count [following 3 days of treatment]

    Assessed by investigator using a slit lamp and counting number of spots.

11. Visual Acuity [following 3 days of treatment]

    The visual acuity score is a count of the number of letters the subject successfully read from the eye chart. The higher the score, the better the vision.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• willing to comply with investigator's and protocol's instructions

• patients signature on the informed consent document

• primary open-angle glaucoma, pigment dispersion or exfoliation glaucoma, or ocular hypertension in at least one eye

• at screening intraocular pressure must be considered to be safe, in both eyes

• in non-qualifying eyes the intraocular pressure should be able to be controlled safely on no pharmacologic therapy or on study medicine alone

• currently treated with one glaucoma medication, untreated intraocular pressure of less than or equal to 28 mm Hg at visit 2 in both eyes

Exclusion Criteria:

• any abnormality preventing reliable applanation tonometry in either eye

• any opacity or subject uncooperativeness that restricts adequate examination of the ocular fundus or anterior chamber in either eye

• any concurrent infectious/noninfectious conjunctivitis, keratitis or uveitis in either eye

• any history of allergic hypersensitivity or poor tolerance to any components of the preparations used in this trial

• females of childbearing potential not using reliable means of birth control

• pregnant or lactating females

• any clinically significant, serious, or severe medical or psychiatric condition

• participation (or current participation) in any investigational drug or device trial within 30 days prior to Visit 1

• severe prior visual acuity or field loss from any cause

• inability to understand the trial procedures, and thus inability to give informed consent

• progressive retinal or optic nerve disease apart from glaucoma

• serious systemic or ocular disease

• intraocular laser surgery within the past three months or corneal or intraocular conventional surgery within the past 6 months

• concurrent use of systemic corticosteroids, by IV, oral, dermal or topical ophthalmic route.

• subjects requiring tear replacement drops or allergy medications with sympathomimetics 24 hours prior to a scheduled study visit

• contraindication to beta-blocker usage including: reactive airway disease, uncontrolled heart failure, or second as well as third degree cardiac block, myasthenia gravis

• any subject the investigator believes will be at risk for glaucomatous progression by their participation in this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bourbonnais	Illinois	United States
2		Charlotte	North Carolina	United States

Sponsors and Collaborators

• Vistakon Pharmaceuticals

Investigators

• Study Director: William C. Stewart, MD, PRN Pharmacuetical Research Network, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vistakon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00804648
• Other Study ID Numbers: VPH0111
• First Posted: Dec 9, 2008
• Last Update Posted: Mar 6, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol; Maleic acid

Study Results

Participant Flow

Arm/Group Title	Hemihydrate/Maleate/Maleate Gel	Maleate/Maleate Gel/Hemihydrate	Maleate Gel/Hemihydrate/Maleate	Hemihydrate/Maleate Gel/Maleate	Maleate/Hemihydrate/Maleate Gel	Maleate Gel/Maleate/Hemihydrate
Arm/Group Description	Period one - Timolol hemihydrate 0.5% Period two - Timolol maleate 0.5% Period three - Timolol maleate gel forming solution 0.5%	Period one - Timolol maleate 0.5% Period two - Timolol maleate gel forming solution 0.5% Period three - Timolol hemihydrate 0.5%	Period one - Timolol maleate gel forming solution 0.5% Period two - Timolol hemihydrate 0.5% Period three - Timolol maleate 0.5%	Period one - Timolol hemihydrate 0.5% Period two - Timolol maleate gel forming solution 0.5% Period three - Timolol maleate 0.5%	Period 1 - Timolol maleate 0.5% Period 2 - Timolol hemihydrate 0.5% Period 3 - Timolol maleate gel forming solution 0.5%	Period 1 - Timolol maleate gel forming solution 0.5% Period 2 - Timolol maleate 0.5% Period 3 - Timolol hemihydrate 0.5%
Period Title: First Intervention
STARTED	3	5	6	4	4	8
COMPLETED	3	5	6	4	4	8
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	3	5	6	4	4	8
COMPLETED	3	5	6	4	4	8
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	3	5	6	4	4	8
COMPLETED	3	5	6	4	4	8
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.3 (8.9)
Sex: Female, Male (Count of Participants)
Female	15 50%
Male	15 50%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Stinging on Instillation
Description	Assessed from subject response to survey question asking about tolerability of medicine upon instillation, using a 0 through 7 scale, with 0=complete comfort and 7=worst pain imaginable.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [Units on a scale]	0.6 (1.0)	1.0 (1.4)	0.6 (1.0)

2. Secondary Outcome

Title	Conjunctival Hyperemia
Description	Assessed by investigator using a slit lamp and a photographic grading scale. Photographs were graded: grade 0, grade 1, grade 2, grade 3. The higher the graded the worse the hyperemia.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [Units on a scale]	0.2 (0.5)	0.4 (0.5)	0.3 (0.5)

3. Secondary Outcome

Title	Tear Film Break-up Time
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [Seconds]	8.5 (6.1)	7.7 (4.9)	8.5 (5.7)

4. Secondary Outcome

Title	Corneal Staining Grade
Description	Assessed by the investigator using a slit lamp and Oxford Scheme, grading 0,1,2,3,4,5. The higher the grade the worse the staining.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [Units on a scale]	1.2 (0.9)	1.1 (0.9)	1.0 (0.8)

5. Secondary Outcome

Title	Corneal Staining Count
Description	Assessed by the investigator using a slit lamp, counting the number of spots.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [Number of spots]	10.5 (12.5)	10.4 (13.4)	8.3 (8.3)

6. Secondary Outcome

Title	Intraoclular Pressure
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [mm of mercury]	16.3 (3.1)	16.2 (2.4)	16.2 (2.2)

7. Secondary Outcome

Title	Basic Schirmer's
Description	Schirmer's measures basic tear function. The higher the number, the less dry the eye.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [mm of moisture]	17.7 (9.7)	14.8 (7.3)	15.4 (6.4)

8. Secondary Outcome

Title	Conjunctival Staining - Nasal Grade
Description	Assessed by investigator using a slit lamp and the Oxford Scheme, grading 0,1,2,3,4,5 according to pictures provided. The higher the grade the worse the staining.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [Units on a scale]	1.2 (0.9)	1.1 (1.0)	1.3 (1.0)

9. Secondary Outcome

Title	Conjunctival Staining - Nasal Count
Description	Assessed by investigator using slit lamp and counting number of spots.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [number of spots]	11.0 (12.5)	10.3 (15.7)	12.9 (14.8)

10. Secondary Outcome

Title	Conjunctival Staining - Temporal Grade
Description	Assessed by investigator using a slit lamp and Oxford Scheme, grading 0,1,2,3,4,5 according to pictures provided. The higher the grade the worse the staining.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [Units on a scale]	0.8 (0.6)	0.7 (0.7)	0.8 (0.7)

11. Secondary Outcome

Title	Conjunctival Staining - Temporal Count
Description	Assessed by investigator using a slit lamp and counting number of spots.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [number of spots]	4.7 (7.3)	4.8 (8.6)	5.3 (6.7)

12. Secondary Outcome

Title	Visual Acuity
Description	The visual acuity score is a count of the number of letters the subject successfully read from the eye chart. The higher the score, the better the vision.
Time Frame	following 3 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Timolol Hemihydrate 0.5%	Timolol Maleate 0.5%	Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
Measure Participants	30	30	30
Mean (Standard Deviation) [number of letters]	52.3 (5.6)	52.5 (6.1)	51.4 (5.8)

Adverse Events

Arm/Group Title	Timolol Hemihydrate 0.5%		Timolol Maleate 0.5%		Timolol Maleate Gel Forming Solution 0.5%
Arm/Group Description
All Cause Mortality
	Timolol Hemihydrate 0.5%		Timolol Maleate 0.5%		Timolol Maleate Gel Forming Solution 0.5%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Timolol Hemihydrate 0.5%		Timolol Maleate 0.5%		Timolol Maleate Gel Forming Solution 0.5%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Timolol Hemihydrate 0.5%		Timolol Maleate 0.5%		Timolol Maleate Gel Forming Solution 0.5%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)		2/30 (6.7%)		0/30 (0%)
Eye disorders
Tearing	2/30 (6.7%)	2	0/30 (0%)	0	0/30 (0%)	0
Blurred Vision	0/30 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Prior to submission for publication or presentation, the PI will provide the Sponsor with at least 60 days for review of a manuscript. If requested in writing, the PI will withhold publication for up to an additional 60 days.