Dose-Ranging Study of the Bimatoprost Ocular Insert

Study Overview
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Brief Summary
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The Bimatoprost Ocular Insert is intended to provide sustained delivery of bimatoprost to the ocular surface to lower the intraocular pressure (IOP) in patients with Open-Angle Glaucoma or Ocular Hypertension. This study evaluated the safety and efficacy of two different doses of the Bimatoprost Ocular Insert, compared to an active control arm with timolol ophthalmic solution (0.5%).

Official Title
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A Phase 2 Prospective, Multicenter, Randomized, Double-masked, Controlled Study to Evaluate the Efficacy and Safety and Dose-response of the Bimatoprost Ocular Insert (2.2 mg, 13 mg) With and Without Concomitant Artificial Tears Compared to a Placebo Ocular Insert With and Without Concomitant Timolol (0.5%) Ophthalmic Solution in Patients With Open-angle Glaucoma or Ocular Hypertension

Conditions
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Primary Open-Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: Bimatoprost
* Drug: Timolol 0.5%
* Device: Placebo Ocular Insert
* Drug: Placebo Eye Drops


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Written informed consent At least 18 years of age Diagnosis in both eyes of either primary open-angle glaucoma (POAG) or ocular hypertension Best corrected-distance visual acuity score equivalent to 20/80 or better Stable visual field Central corneal thickness between 490 - 620 micrometers Inclusion Criteria at the Randomization Visit: (T is defined as time and hr is defined as hour[s]) IOP for each eye is ≥ 23 mm Hg at T=0 hr, ≥ 20 mm Hg at T=2 hr and T=8 hr. Inter-eye IOP difference of ≤ 5.0 mm Hg at T=0 hr, T=2 hr and T=8 hr. IOP for each eye is ≤ 30 mm Hg at T=0 hr, T=2 hr and T=8 hr. Key Exclusion Criteria: Any known contraindication to prostaglandin analog (latanoprost, travoprost, bimatoprost, tafluprost) or timolol A cardiac or pulmonary condition that in the opinion of the Investigator would contraindicate the use of beta-blocker drops Cup-to-disc ratio of greater than 0.8 Significant risk of angle closure due to pupil dilation, defined as a Shaffer classification of less than Grade 2 based on gonioscopy Ocular, orbital, and/or eyelid surgery of any type within the past six (6) months from screening date Laser surgery for glaucoma / ocular hypertension on one (1) or both eyes within the last six (6) months Past history of any incisional surgery for glaucoma at any time Past history of corneal refractive surgery Corneal abnormalities that would interfere with accurate IOP readings with an applanation tonometer Current participation in an investigational drug or device study or participation in such a study within 30 days of Screening Inability to adequately evaluate the retina Participants who will require contact lens use during the study period. Participants who currently have punctal occlusion Pregnant, lactating or of child-bearing potential and not using a medically acceptable form of birth control

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 13 mg Bimatoprost Ocular Insert<br>Washout + Placebo Ocular Insert in each eye for 4 to 6 weeks, followed by 13 mg Bimatoprost Ocular Insert in each eye (OU) for 12 weeks. Note: participants also self-administered placebo ophthalmic eye drops to each eye twice a day (BID) for the first 6 weeks. After 12 weeks, 13 mg Bimatoprost Ocular Insert in each eye for an additional 12 weeks. | Drug: Bimatoprost<br>* Bimatoprost sustained release Ocular Insert<br>Device: Placebo Ocular Insert<br>* Placebo ocular insert OU.<br>Drug: Placebo Eye Drops<br>* Placebo eye drops BID OU.<br>|
| Experimental: 2.2 mg Bimatoprost Ocular Insert<br>Washout + Placebo Ocular Insert in each eye for 4 to 6 weeks, followed by 2.2 mg Bimatoprost Ocular Insert in each eye for 12 weeks. Note: participants also self-administered placebo ophthalmic eye drops in each eye twice a day for the first 6 weeks. After 12 weeks, 13 mg Bimatoprost Ocular Insert in each eye for an additional 12 weeks. | Drug: Bimatoprost<br>* Bimatoprost sustained release Ocular Insert<br>Device: Placebo Ocular Insert<br>* Placebo ocular insert OU.<br>Drug: Placebo Eye Drops<br>* Placebo eye drops BID OU.<br>|
| Active Comparator: Timolol 0.5%<br>Washout + Placebo Ocular Insert in each eye for 4 to 6 weeks, followed by 0.5% timolol ophthalmic solution in each eye for 6 weeks. Note: participants simultaneously wore placebo ocular inserts for 12 weeks. After 12 weeks, 13 mg Bimatoprost Ocular Insert in each eye for an additional 12 weeks. | Drug: Bimatoprost<br>* Bimatoprost sustained release Ocular Insert<br>Drug: Timolol 0.5%<br>* BID drops OU, 0.5% ophthalmic solution<br>Device: Placebo Ocular Insert<br>* Placebo ocular insert OU.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Intraocular Pressure (IOP) at Week 8 | IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 8. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated an improvement. | Baseline (Day 0) to Week 8 | 
| Change From Baseline in IOP at Week 12 | IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 12. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated an improvement. | Baseline (Day 0) to Week 12 | 
| Percentage of Participants by Change From Baseline in Best-corrected Visual Acuity (BCVA) Categories at Week 8 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. | Baseline (Day 0) to Week 8 | 
| Percentage of Participants by Change From Baseline in Best-corrected Visual Acuity (BCVA) Categories at Week 12 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. | Baseline (Day 0) to Week 12 | 
| Percentage of Participants With Clinically Significant Change From Baseline in Slit-Lamp Examination Findings at Week 12 | The clinician examined and graded the eyelids, conjunctiva, cornea and anterior chamber of the eye with the aid of a slit-lamp, (conjunctival erythema was assessed as part of the examination). Fluorescein dye was instilled into the ocular cul-de-sac to facilitate this examination. | Baseline (Day 0) to Week 12 | 
| Change From Baseline in Automated Visual Field at Week 12 | Automated Visual Field was examined used the Humphrey Visual Field Analyzer, a test that measures the entire area of peripheral vision that can be seen while the eye is focused on a central point. A positive change from Baseline indicates improvement. | Baseline (Day 0) to Week 12 | 
| Dilated Fundus Exam: Cup-to-Disc-Ratio | The cup-to-disk-ratio is an eye test to assess the progression of glaucoma. The diameter of the cup is compared to the diameter of the disk and a ratio is determined. The normal cup-disk ratio is 0.3. An increase in the cup-to-disc-ratio is a possible indication of glaucoma. | Week 12 | 
| Percentage of Participants by Dilated Fundus Exam Pathology Grade at Week 12 | Dilated fundus examination pathology findings were noted, described and graded on a scale of None (0), Mild (+1), Moderate (+2) and Severe (+3). The percentage of participants in each grade is reported. | Week 12 | 
| Percentage of Participants With Ocular and Non-ocular Adverse Events (AE) by Severity in Period A/B | An AE was defined as any untoward medical occurrence (eg, sign, symptom, disease, syndrome, intercurrent illness) that occurred in a study participant, regardless of the suspected cause during the study. An ocular AE is an AE that occurred in the eye and non-ocular is an AE that occurred not in the eye. Th investigator assessed the worst severity of each AE as: Mild=aware of sign or symptom, but readily tolerated, Moderate=discomfort enough to cause interference with usual activity or Severe=incapacitating with inability to work or do usual activity. | Baseline (Day 0) to Week 12 | 
| Percentage of Participants With Ocular and Non-ocular Adverse Events (AE) by Severity in Period C | An AE was defined as any untoward medical occurrence (eg, sign, symptom, disease, syndrome, intercurrent illness) that occurred in a study participant, regardless of the suspected cause during the study. An ocular AE is an AE that occurred in the eye and non-ocular is an AE that occurred not in the eye. The investigator assessed the worst severity of each AE as: Mild=aware of sign or symptom, but readily tolerated, Moderate=discomfort enough to cause interference with usual activity or Severe=incapacitating with inability to work or do usual activity. | Week 12 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in IOP at Week 2 | IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 2. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated an improvement. | Baseline (Day 0) to Week 2 | 
| Change From Baseline in IOP at Week 6 | IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Week 6. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated an improvement. | Baseline (Day 0) to Week 6 | 
| Change From Baseline in IOP in Period C | IOP is a measurement of the fluid pressure inside the eye. Diurnal IOP measurements were taken at 8 am (T=0 hour), 10 am (T=2 hour), and 4 pm (T=8 hour) at Weeks 14, 18 and 24. IOP readings from both eyes were averaged to compute a single IOP value for each diurnal timepoint. A negative change from Baseline indicated an improvement. | Baseline (Day 0) to Weeks 14, 18 and 24 |