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

Conditions

Open-Angle Glaucoma, Ocular Hypertension

Brief summary

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.

Related papers

No related papers found yet.

Interventions

DRUGFixed Combination

Continuous elution from the ocular insert.

DRUGBimatoprost

Continuous elution from the ocular insert. This is an active control arm.

DRUGTimolol

Continuous elution from the ocular insert. This is an active control arm.

DEVICEPlacebo Segment

One segment of placebo (no drug product)

DRUGTimolol 0.5%

0.5% timolol drops twice daily.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
IOP on Day 16	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.
IOP on Day 49	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.
IOP on Day 70	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.
Intraocular Pressure (IOP) on Day 8	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.
IOP on Day 28	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.

Secondary

Measure	Time frame	Description
IOP During Open Label Period	Day 98, Day 112	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.
Number of Participants With Ocular and Non-Ocular Adverse Events	From Randomization (Day 0) to Day 70	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.

Countries

Panama

Participant flow

Participants by arm

Arm	Count
Fixed Combination (FC) Ocular Inset Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	17
Bimatoprost Ocular Insert Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	17
Timolol Ocular Insert Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	16
Total	50

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG004
Double-Blind Treatment Period	Adverse Event	0	1	0
Open-Label Period	Lost to Follow-up	0	0	1
Pre-Randomization Washout Period	Washout/Randomization Failure	5	0	0

Baseline characteristics

Characteristic	Fixed Combination (FC) Ocular Inset	Bimatoprost Ocular Insert	Timolol Ocular Insert	Total
Age, Continuous	67.24 years STANDARD_DEVIATION 12.94	68.94 years STANDARD_DEVIATION 5.75	67.56 years STANDARD_DEVIATION 9.27	67.92 years STANDARD_DEVIATION 9.61
Intraocular Pressure (IOP) Randomization (T=0 hour)	24.34 mm Hg STANDARD_DEVIATION 2.06	24.30 mm Hg STANDARD_DEVIATION 1.89	24.18 mm Hg STANDARD_DEVIATION 1.78	24.27 mm Hg STANDARD_DEVIATION 1.88
Intraocular Pressure (IOP) Randomization (T=4 hour)	22.98 mm Hg STANDARD_DEVIATION 2.92	22.93 mm Hg STANDARD_DEVIATION 3.06	23.33 mm Hg STANDARD_DEVIATION 2.77	23.07 mm Hg STANDARD_DEVIATION 2.87
Intraocular Pressure (IOP) Randomization (T=8 hour)	22.44 mm Hg STANDARD_DEVIATION 2.57	22.90 mm Hg STANDARD_DEVIATION 3.13	23.03 mm Hg STANDARD_DEVIATION 2.7	22.78 mm Hg STANDARD_DEVIATION 2.77
Sex: Female, Male Female	14 Participants	11 Participants	11 Participants	36 Participants
Sex: Female, Male Male	3 Participants	6 Participants	5 Participants	14 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 17	0 / 17	0 / 16
other Total, other adverse events	16 / 17	16 / 17	11 / 16
serious Total, serious adverse events	2 / 17	1 / 17	0 / 16