ClinicalTrials.gov
ClinicalTrials.gov Menu

BOL-303259-X With Timolol 0.5% in Subjects With Open-Angle Glaucoma or Ocular Hypertension (Constellation)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01707381
Recruitment Status : Completed
First Posted : October 16, 2012
Results First Posted : September 3, 2018
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
Bausch & Lomb Incorporated

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Ocular Hypertension
Open Angle Glaucoma
Interventions Drug: BOL-303259-X
Drug: Timolol maleate
Enrollment 25
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Timolol Maleate Cross Over to BOL-303259X BOL-303259-X Crossover to Timolol Maleate
Hide Arm/Group Description Participants first recieved timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks. Thereafter they received BOL-303259X once in the evening for 4 weeks. Participants first received BOL-303259-X topical ophthalmic solution administered 1 drop QD in the evening for 4 weeks. Thereafter, they received timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks.
Period Title: Period 1
Started 12 13
Completed 10 11
Not Completed 2 2
Period Title: Period 2
Started 10 11
Completed 10 11
Not Completed 0 0
Arm/Group Title All Study Participants
Hide Arm/Group Description Participants who were randomized to receive either latanoprostene ophthalmic solution 0.024% or timolol maleate 0.5%
Overall Number of Baseline Participants 21
Hide Baseline Analysis Population Description
ITT Population: All randomized subjects who received at least one dose of study drug, had a baseline and at least one postbaseline intraocular assessment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
<=18 years
0
   0.0%
Between 18 and 65 years
13
  61.9%
>=65 years
8
  38.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants
61.0  (11.13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Female
14
  66.7%
Male
7
  33.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Hispanic or Latino
4
  19.0%
Not Hispanic or Latino
17
  81.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
American Indian or Alaska Native
1
   4.8%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   9.5%
White
18
  85.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Treatment-Naive  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
15
  71.4%
1.Primary Outcome
Title 24 Hour IOP
Hide Description Supine intraocular pressure (IOP) measured in the study eye following 4 weeks of treatment
Time Frame after 4 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population:All randomized subjects who received at least one dose of study drug, had a baseline and at least one postbaseline intraocular assessment.
Arm/Group Title Timolol Maleate BOL-303259-X
Hide Arm/Group Description:

Timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks.

Timolol maleate: Topical ophthalmic solution

BOL-303259-X topical ophthalmic solution administered 1 drop QD in the evening for 4 weeks.

BOL-303259-X: Topical ophthalmic solution

Overall Number of Participants Analyzed 21 21
Least Squares Mean (Standard Deviation)
Unit of Measure: mm Hg
23.55  (2.46) 21.77  (2.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Timolol Maleate, BOL-303259-X
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.773
Confidence Interval (2-Sided) 95%
-2.380 to -1.166
Estimation Comments Treatment Difference = BOL-303259-X 0.024% - Timolol maleate 0.5%.
2.Secondary Outcome
Title 24-hour Ocular Perfusion Pressure
Hide Description Sitting Ocular Perfusion Pressure = 95/140 x mean arterial blood pressure - IOP; Supine Ocular Perfusion Pressure = 115/130 x mean arterial blood pressure - IOP; the nocturnal time frame encompassed measures taken at 10pm, 12am, 2am and 4 am; whereas the diurnal time frame encompassed measures taken at 6am, 8am, 10am, 12pm, 2pm, 4pm, 6pm, and 8pm.
Time Frame after 4 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT): All randomized subjects who received at least one dose of study drug, had a baseline, and at least one post baseline intraocular assessment.
Arm/Group Title Timolol Maleate BOL-303259-X
Hide Arm/Group Description:

Timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks.

Timolol maleate: Topical ophthalmic solution

BOL-303259-X topical ophthalmic solution administered 1 drop QD in the evening for 4 weeks.

BOL-303259-X: Topical ophthalmic solution

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: mm Hg
OPP (nocturnal) 48.4  (9.4) 52.5  (9.5)
OPP (Diurnal supine) 54.8  (7.5) 55.9  (7.8)
OPP (Diurnal sitting) 43.2  (5.7) 45.2  (6.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Timolol Maleate, BOL-303259-X
Comments Statistical analysis of nocturnal (supine) OPP was performed among baseline, the BOL-303259-X treatment and timolol treatment using ANOVA. the criteria for statistical significance was P<0.05. Post hoc Bonferroni T-tests were then utilized to compare BOL and timolol groups.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Bonferroni t-test used for paired compar
Estimated Value 0.010
Estimation Comments the bonferroni result applies to nocturnal supine OPP data comparing BOL group to timolol group
3.Secondary Outcome
Title IOP Area Under the Curve Over 24 Hours
Hide Description The Area Under the Curve(AUC) is the weighted average of IOP over all 24-hour IOP assessment times (2pm, 4pm, 6pm, 8pm, 10pm, 12am, 2am, 4am, 6am, 8am, 10am, 12pm). The AUC was calculated using the trapezoidal rule.
Time Frame after 4 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Timolol Maleate BOL-303259-X
Hide Arm/Group Description:

Timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks.

Timolol maleate: Topical ophthalmic solution

BOL-303259-X topical ophthalmic solution administered 1 drop QD in the evening for 4 weeks.

BOL-303259-X: Topical ophthalmic solution

Overall Number of Participants Analyzed 21 21
Least Squares Mean (Standard Deviation)
Unit of Measure: mm Hg
23.54  (2.44) 21.77  (2.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Timolol Maleate, BOL-303259-X
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.770
Confidence Interval (2-Sided) 95%
-2.915 to -0.625
Estimation Comments Treatment Difference = BOL-303259-X 0.024% - Timolol maleate 0.5%.
Time Frame Four weeks for each intervention
Adverse Event Reporting Description Safety population included all participants who received at least one dose of intervention
 
Arm/Group Title Timolol Maleate BOL-303259-X
Hide Arm/Group Description

Timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks.

Timolol maleate: Topical ophthalmic solution

BOL-303259-X topical ophthalmic solution administered 1 drop QD in the evening for 4 weeks.

BOL-303259-X: Topical ophthalmic solution

All-Cause Mortality
Timolol Maleate BOL-303259-X
Affected / at Risk (%) Affected / at Risk (%)
Total   0/23 (0.00%)   0/23 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Timolol Maleate BOL-303259-X
Affected / at Risk (%) Affected / at Risk (%)
Total   0/23 (0.00%)   0/23 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Timolol Maleate BOL-303259-X
Affected / at Risk (%) Affected / at Risk (%)
Total   4/23 (17.39%)   1/23 (4.35%) 
Cardiac disorders     
Dizziness  1  1/23 (4.35%)  0/23 (0.00%) 
Dyspnoea  1  1/23 (4.35%)  0/23 (0.00%) 
Eye disorders     
Punctate keratitis  1  3/23 (13.04%)  0/23 (0.00%) 
Gastrointestinal disorders     
Nausea  1  1/23 (4.35%)  1/23 (4.35%) 
General disorders     
Instillation site erythema  1  0/23 (0.00%)  1/23 (4.35%) 
Instillation site irritations  1  1/23 (4.35%)  0/23 (0.00%) 
hyperhidrosis  1  0/23 (0.00%)  1/23 (4.35%) 
Investigations     
Blood pressure decreased  1  1/23 (4.35%)  0/23 (0.00%) 
Heart rate decreased  1  1/23 (4.35%)  0/23 (0.00%) 
1
Term from vocabulary, MedDRA (13.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Heleen DeCory, Ph.D.
Organization: Bausch + Lomb
Phone: (585) 338-8161
Responsible Party: Bausch & Lomb Incorporated
ClinicalTrials.gov Identifier: NCT01707381     History of Changes
Other Study ID Numbers: 803
First Submitted: October 12, 2012
First Posted: October 16, 2012
Results First Submitted: June 11, 2018
Results First Posted: September 3, 2018
Last Update Posted: September 3, 2018