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In participants with a diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT), the primary objective is to demonstrate that the mean IOP reduction after 3 months of treatment with BOL-303259-X once daily (QD) is non-inferior to timolol maleate 0.5% twice daily (BID). The secondary objective is to demonstrate the superiority of BOL-303259-X QD to timolol maleate 0.5% BID. This assessment will be performed if the non-inferiority of BOL-303259-X QD to timolol maleate 0.5% BID is determined. An open label safety phase will be conducted at the end of Visit 6 (3 months) where all participants will receive BOL-303259-X QD for an additional 3 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BOL-303259-X | Experimental | BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye(s). |
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| Timolol | Active Comparator | Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye(s). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BOL-303259-X | Drug | BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning |
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| Measure | Description | Time Frame |
|---|---|---|
| Mean IOP | 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). | 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) |
| Measure | Description | Time Frame |
|---|---|---|
| IOP ≤ 18 mm Hg | Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months | 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) |
| IOP Reduction ≥ 25% |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Ocular and Systemic Adverse Events | 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. | 6 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jason Vittitow | Bausch & Lomb Incorporated | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bausch & Lomb Inc. | Rochester | New York | 14609 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27210275 | Result | Medeiros FA, Martin KR, Peace J, Scassellati Sforzolini B, Vittitow JL, Weinreb RN. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study. Am J Ophthalmol. 2016 Aug;168:250-259. doi: 10.1016/j.ajo.2016.05.012. Epub 2016 May 20. | |
| 29194198 | Result |
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| ID | Title | Description |
|---|---|---|
| FG000 | BOL-303259-X | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Timolol | Drug | Timolol will be administered BID once in the morning and once in the evening. |
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| BOL-303259-X | Drug | All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7). |
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Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months
| 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) |
| Weinreb RN, Liebmann JM, Martin KR, Kaufman PL, Vittitow JL. Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings. J Glaucoma. 2018 Jan;27(1):7-15. doi: 10.1097/IJG.0000000000000831. |
| FG001 | Timolol | 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). |
| COMPLETED |
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| NOT COMPLETED |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | BOL-303259-X | 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). |
| BG001 | Timolol | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Mean IOP | 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). | Intent-to-treat population with LOCF | Posted | Least Squares Mean | Standard Deviation | mm Hg | 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) |
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| Secondary | IOP ≤ 18 mm Hg | Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months | Intent-to treat population with LOCF | Posted | Count of Participants | Participants | 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) |
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| Secondary | IOP Reduction ≥ 25% | Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months | Intent-to-treat population with LOCF | Posted | Count of Participants | Participants | 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) |
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| Other Pre-specified | Number of Participants With Ocular and Systemic Adverse Events | 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. | Safety population. Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population | Posted | Count of Participants | Participants | 6 months |
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6 months
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BOL-303259-X | BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye during the efficacy phase | 4 | 279 | 50 | 279 | ||
| EG001 | Timolol | Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye during the efficacy phase. | 0 | 136 | 12 | 136 | ||
| EG002 | BOL-303259-X Safety Extension 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 | 2 | 384 | 32 | 384 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| left shoulder subluxation of acromioclavicular joint | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
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| Scapular fracture | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
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| Uncontrolled hypertension | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
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| Chest pain | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
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| Cholelethiasis | Hepatobiliary disorders | MedDRA (13.0) | Systematic Assessment |
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| head injury | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
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| Other convulsions | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
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| Pain in joint (shoulder) | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
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| Subarachnoid hemorrhage | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
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| Subdural hermorrhage | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
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| Closed dislocation of finger | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
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| Closed fracture of distal end of ulna | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctival hyperemia | Eye disorders | MedDRA (13.0) | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA (13.0) | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA (13.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| H. DeCory, Director Medical Affairs | Bausch + Lomb, a division of Valeant Pharmaceuticals | 585 732-3284 | heleen_H_decory@bausch.com |
| ID | Term |
|---|---|
| D005902 | Glaucoma, Open-Angle |
| D009798 | Ocular Hypertension |
| ID | Term |
|---|---|
| D005901 | Glaucoma |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| C568859 | BOL 303259-X |
| D013999 | Timolol |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D013830 | Thiadiazoles |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009025 | Morpholines |
| D010078 | Oxazines |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| 12 pm week 2 |
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| 4 pm week 2 |
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| 8 am week 6 |
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| 12 pm week 6 |
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| 4 pm week 6 |
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| 8 am Month 3 |
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| 12 pm Month 3 |
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| 4 pm Month 3 |
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