A Study to Evaluate Efficacy and Safety of a Fixed Combination Ocular Insert in Participants With Open-angle Glaucoma or Ocular Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to determine if a combination of two drugs (bimatoprost and timolol) delivered to the surface of the eye over 10 weeks is better at lowering intraocular pressure (IOP) than either of the drugs delivered alone.

Official Title
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A Phase 1B, Multicenter, Randomized, Double-masked, Controlled Study to Evaluate the Efficacy and Safety of a Fixed Combination Bimatoprost/Timolol Ocular Insert Compared to Its Individual Components With Crossover to Timolol 0.5% in Subjects With Open-angle Glaucoma (OAG) or Ocular Hypertension (OHT)

Conditions
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Open-Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: Fixed Combination
* Drug: Bimatoprost
* Drug: Timolol
* Device: Placebo Segment
* Drug: Timolol 0.5%


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: IOP for each eye is ≥ 23 mmHg at T=0hr, ≥ 20 mmHg at T=4hr and T=8hr. Inter-eye IOP difference of ≤ 5.0 mmHg at T=0hr, T=4hr and T=8hr. IOP for each eye is ≤ 30 mmHg at T=0hr, T=4hr and T=8hr. 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 a topical beta-blocker Use of any agents known to have a substantial effect on IOP during planned study period (e.g. beta-blockers) 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 7 days of Screening Inability to adequately evaluate the retina Subjects who will require contact lens use during the study period. Subjects 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed Combination (FC) Ocular Insert<br>Washout plus Placebo Ocular Insert in each eye for 24 to 48 days, followed by one segment of bimatoprost and one segment of timolol maleate combined onto a single ocular insert in each eye for 70 days. Following a second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112. | Drug: Fixed Combination<br>* Continuous elution from the ocular insert.<br>* Other names: Bimatoprost-Timolol combination;Device: Placebo Segment<br>* One segment of placebo (no drug product)<br>Drug: Timolol 0.5%<br>* 0.5% timolol drops twice daily.<br>|
| Experimental: Bimatoprost Ocular Insert<br>Washout plus Placebo Ocular Insert in each eye for 24 to 48 days, followed by one segment of bimatoprost and one placebo segment (no drug product) combined onto a single ocular insert in each eye for 70 days. Following a second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112. | Drug: Bimatoprost<br>* Continuous elution from the ocular insert. This is an active control arm.<br>* Other names: Bimatoprost component only;Device: Placebo Segment<br>* One segment of placebo (no drug product)<br>Drug: Timolol 0.5%<br>* 0.5% timolol drops twice daily.<br>|
| Experimental: Timolol Ocular Insert<br>Washout plus Placebo Ocular Insert in each eye for 24 to 48 days, followed by one segment of timolol and one placebo segment (no drug product) combined onto a single ocular insert in each eye for 70 days. Following a second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112. | Drug: Timolol<br>* Continuous elution from the ocular insert. This is an active control arm.<br>* Other names: Timolol component only;Device: Placebo Segment<br>* One segment of placebo (no drug product)<br>Drug: Timolol 0.5%<br>* 0.5% timolol drops twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular Pressure (IOP) on Day 8 | IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour). The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint. | Day 8 | 
| IOP on Day 16 | IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour). The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint. | Day 16 | 
| IOP on Day 28 | IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour). The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint. | Day 28 | 
| IOP on Day 49 | IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour). The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint. | Day 49 | 
| IOP on Day 70 | IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour). The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint. | Day 70 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Ocular and Non-Ocular Adverse Events | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with adverse events related to the eye as well as number of participants with all other adverse events. | From Randomization (Day 0) to Day 70 | 
| IOP During Open Label Period | IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour) at the start (Day 98) and end (Day 112) of the Open Label Period during which participants were treated with timolol 0.5% ophthalmic solution twice daily. The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint. | Day 98, Day 112 |