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Comparing the Safety and Efficacy of BOL-303259-X Ophthalmic Solution With Timolol Maleate Ophthalmic Solution in Subjects With Open-Angle Glaucoma or Ocular Hypertension (LUNAR)

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ClinicalTrials.gov Identifier: NCT01749930
Recruitment Status : Completed
First Posted : December 17, 2012
Results First Posted : November 21, 2018
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Bausch & Lomb Incorporated

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Open-Angle Glaucoma
Ocular Hypertension
Interventions Drug: BOL-303259-X
Drug: Timolol
Enrollment 420

Recruitment Details  
Pre-assignment Details  
Arm/Group Title BOL-303259-X Timolol
Hide Arm/Group Description

BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye(s).

BOL-303259-X: BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning

BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).

Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye(s).

Timolol: Timolol will be administered BID once in the morning and once in the evening.

BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).

Period Title: Overall Study
Started 283 [1] 137 [1]
Completed 253 [1] 125 [1]
Not Completed 30 12
[1]
randomized population
Arm/Group Title BOL-303259-X Timolol Total
Hide Arm/Group Description

BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye(s).

BOL-303259-X: BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning

BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).

Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye(s).

Timolol: Timolol will be administered BID once in the morning and once in the evening.

BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).

Total of all reporting groups
Overall Number of Baseline Participants 278 136 414
Hide Baseline Analysis Population Description
Intent-to-treat population. Of the 420 subjects randomized, 5 subjects did not receive any instillation of study medication. The safety population consisted of 415 subjects, whereas the ITT population consisted of 414 subjects.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 278 participants 136 participants 414 participants
65.0  (9.77) 64.1  (9.71) 64.7  (9.75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 136 participants 414 participants
Female
162
  58.3%
79
  58.1%
241
  58.2%
Male
116
  41.7%
57
  41.9%
173
  41.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 136 participants 414 participants
Hispanic or Latino
36
  12.9%
19
  14.0%
55
  13.3%
Not Hispanic or Latino
242
  87.1%
117
  86.0%
359
  86.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 136 participants 414 participants
American Indian or Alaska Native
1
   0.4%
0
   0.0%
1
   0.2%
Asian
4
   1.4%
1
   0.7%
5
   1.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
69
  24.8%
46
  33.8%
115
  27.8%
White
204
  73.4%
89
  65.4%
293
  70.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Mean IOP
Hide Description Mean intraocular pressure (IOP) in the study eye measured at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3).
Time Frame 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with LOCF
Arm/Group Title BOL-303259-X Timolol
Hide Arm/Group Description:
BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye.
Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye.
Overall Number of Participants Analyzed 277 135
Least Squares Mean (Standard Deviation)
Unit of Measure: mm Hg
8 am week 2 Number Analyzed 275 participants 134 participants
19.17  (3.748) 19.61  (3.092)
12 pm week 2 Number Analyzed 270 participants 134 participants
18.46  (3.327) 19.22  (3.241)
4 pm week 2 Number Analyzed 270 participants 134 participants
18.10  (3.135) 18.79  (3.022)
8 am week 6 Number Analyzed 277 participants 135 participants
18.67  (3.272) 19.59  (3.324)
12 pm week 6 Number Analyzed 271 participants 135 participants
18.02  (3.073) 18.86  (3.169)
4 pm week 6 Number Analyzed 271 participants 135 participants
17.87  (3.114) 18.85  (3.415)
8 am Month 3 Number Analyzed 277 participants 135 participants
18.68  (3.195) 19.56  (3.318)
12 pm Month 3 Number Analyzed 271 participants 135 participants
17.92  (3.119) 19.21  (3.129)
4 pm Month 3 Number Analyzed 271 participants 135 participants
17.72  (3.153) 19.06  (3.002)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOL-303259-X, Timolol
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The 2 treatments were compared for each time point by visit. LS mean of each treatment group, the difference in the LS mean, and the 2-sided 95% CI for the difference were obtained. Noninferiority could be claimed if the upper limit of the CIs <1.5 mmHg at all time points of each visit and <1.00 mmHg for at least 5 out of the 9 time points. If noninferiority was determined, superiority at each time point could be claimed if the upper limit of the 95% CI<0 mmHg at all time points of each visit.
Statistical Test of Hypothesis P-Value 0.216
Comments The ANCOVA results for the comparison of LS means of mean IOP between treatment groups demonstrated noninferiority of BOL-303259-X to timolol. Superiority of BOL-303259-X to timolol was demonstrated at 8 of 9 time points (exception at 8 am Week 2).
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title IOP ≤ 18 mm Hg
Hide Description Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months
Time Frame 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to treat population with LOCF
Arm/Group Title BOL-303259-X Timolol
Hide Arm/Group Description:
BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye.
Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye.
Overall Number of Participants Analyzed 277 135
Measure Type: Count of Participants
Unit of Measure: Participants
49
  17.7%
15
  11.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOL-303259-X, Timolol
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.084
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
3.Secondary Outcome
Title IOP Reduction ≥ 25%
Hide Description Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months
Time Frame 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with LOCF
Arm/Group Title BOL-303259-X Timolol
Hide Arm/Group Description:
BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye.
Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye.
Overall Number of Participants Analyzed 277 135
Measure Type: Count of Participants
Unit of Measure: Participants
86
  31.0%
25
  18.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOL-303259-X, Timolol
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Other Pre-specified Outcome
Title Number of Participants With Ocular and Systemic Adverse Events
Hide Description Following assessments through 3 months (Visit 6), all participants, irrespective of previous randomization, converted to a single open label safety arm receiving BOL-303259-X QD in the evening for an additional 3 months through Visit 7. Adverse events were recorded throughout the comparative efficacy phase and open label extension phase.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population. Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population
Arm/Group Title BOL-303259-X Timolol BOL-303259-X Safety Extension Phase
Hide Arm/Group Description:
BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye during the efficacy phase
Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye during the efficacy phase
Following completion of the efficacy phase, all subjects were converted to BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label safety extension phase
Overall Number of Participants Analyzed 279 136 384
Measure Type: Count of Participants
Unit of Measure: Participants
>/= 1 nonocular AE
36
  12.9%
18
  13.2%
23
   6.0%
>/= 1 ocular (Study eye) AE
66
  23.7%
18
  13.2%
53
  13.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOL-303259-X, Timolol
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Time Frame 6 months
Adverse Event Reporting Description

Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population.

All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.

 
Arm/Group Title BOL-303259-X Timolol BOL-303259-X Safety Extension Phase
Hide Arm/Group Description BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye during the efficacy phase Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye during the efficacy phase. Following completion of the efficacy phase, all subjects were converted to BL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label extension phase
All-Cause Mortality
BOL-303259-X Timolol BOL-303259-X Safety Extension Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
BOL-303259-X Timolol BOL-303259-X Safety Extension Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/279 (1.43%)      0/136 (0.00%)      2/384 (0.52%)    
Cardiac disorders       
Coronary artery disease  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Chest pain  1  0/279 (0.00%)  0 0/136 (0.00%)  0 1/384 (0.26%)  1
Hepatobiliary disorders       
Cholelethiasis  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Injury, poisoning and procedural complications       
left shoulder subluxation of acromioclavicular joint  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Scapular fracture  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Fall  1  2/279 (0.72%)  2 0/136 (0.00%)  0 0/384 (0.00%)  0
head injury  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Subdural hermorrhage  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Closed dislocation of finger  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Closed fracture of distal end of ulna  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Pain in joint (shoulder)  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Nervous system disorders       
Other convulsions  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Subarachnoid hemorrhage  1  1/279 (0.36%)  1 0/136 (0.00%)  0 0/384 (0.00%)  0
Vascular disorders       
Uncontrolled hypertension  1  0/279 (0.00%)  0 0/136 (0.00%)  0 1/384 (0.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
BOL-303259-X Timolol BOL-303259-X Safety Extension Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   50/279 (17.92%)      12/136 (8.82%)      32/384 (8.33%)    
Eye disorders       
Conjunctival hyperemia  1  25/279 (8.96%)  32 1/136 (0.74%)  1 18/384 (4.69%)  19
Eye irritation  1  20/279 (7.17%)  20 6/136 (4.41%)  7 8/384 (2.08%)  8
Eye pain  1  16/279 (5.73%)  16 5/136 (3.68%)  6 6/384 (1.56%)  7
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
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: H. DeCory, Director Medical Affairs
Organization: Bausch + Lomb, a division of Valeant Pharmaceuticals
Phone: 585 732-3284
Responsible Party: Bausch & Lomb Incorporated
ClinicalTrials.gov Identifier: NCT01749930     History of Changes
Other Study ID Numbers: 770
First Submitted: December 11, 2012
First Posted: December 17, 2012
Results First Submitted: May 2, 2018
Results First Posted: November 21, 2018
Last Update Posted: November 21, 2018