Ocular Hypertension (OHT), Primary Open-Angle Glaucoma (POAG)
Conditions
Keywords
glaucoma, primary open-angle glaucoma, ocular hypertension, adenosine agonist, eye drop, trabodenoson, trabecular meshwork
Brief summary
Phase II, randomized, double-masked study to evaluate the efficacy and tolerability of topical ocular delivery of fixed-dosed combinations of trabodenoson and latanoprost in subjects with Ocular Hypertension or Primary Open-Angle Glaucoma. All subjects who meet the study's enrollment criteria following Screening will undergo washout of all prohibited medications (if washout is needed), including their routine glaucoma medications. During the Placebo Run-In Period, placebo is applied twice daily to both eyes in all subjects. During the Treatment Period, study drug is applied to both eyes for a total of 8 weeks. Each subject will be assigned 4 weeks of AM and 4 weeks of PM dosing in a masked manner. AM vs PM dosing is masked utilizing Placebo in addition to the active drug product. During the Treatment Period, study drug (Active and Placebo) eye drop applications will occur twice daily, in the morning and in the evening. The Treatment Period will be followed by an Observation Period of approximately 7 days wherein no study eye drops are instilled. The purpose of the study is to assess the overall benefit/risk profile of binocular topical application of different doses of trabodenoson (3.0% and 6.0%) when combined with latanoprost (0.005% or 0.0025%) one drop daily (QD) for 8 weeks.
Detailed description
This is a phase II, randomized, double-masked study to evaluate the efficacy and tolerability of topical ocular delivery of fixed-dose combinations of trabodenoson and latanoprost in subjects with OHT or POAG. The Primary Objective of this Trial is to evaluate the efficacy of different topical ocular doses of trabodenoson (3.0% and 6.0%) when added to latanoprost (0.005% or 0.0025%), one drop daily to both eyes over two consecutive 4 week periods. The Secondary Objective is to evaluate the tolerability and safety of different doses of trabodenoson (3.0% and 6.0%) when added to latanoprost (0.005% or 0.0025%), one drop daily to both eyes over two consecutive 4 week periods. the Hypotheses is that topical ocular co-administration of 3.0% or 6.0% trabodenoson plus latanoprost 0.0025% or 0.005% ophthalmic formulation will reduce IOP and be well-tolerated. All subjects who meet the study's enrollment criteria following Screening will undergo washout of all prohibited medications, including their routine glaucoma medications. During the Placebo Run-In Period, placebo (vehicle control matched to trabodenoson) is applied twice daily to both eyes in all subjects. During the Treatment Period, study drug is applied to both eyes for a total of 8 weeks. Each subject will be assigned 4 weeks of AM and 4 weeks of PM dosing in a manner that is masked to the patient. The Treatment Period will be followed by an Observation Period of approximately 7 days wherein no study eye drops are instilled. To mimic what is generally seen in clinical trials, the number of subjects with ocular hypertension as their diagnosis will be limited to approximately 30% of the total subjects enrolled. Additionally, so the trial mirrors the general population demographics (so as to improve generalizability of the results) the proportion of African American subjects will be approximately 25% or less but not less than 12% of the total subjects enrolled. The purpose of the study is to assess the efficacy, tolerability, and safety of binocular topical application of different doses of trabodenoson (3.0% and 6.0%) when added to latanoprost (0.005% or 0.0025%) one drop daily over two consecutive 4 week periods in subjects with POAG or OHT. Data collection will include efficacy (masked-IOPs), local (ophthalmic) and systemic tolerability and safety assessments
Interventions
DRUGtrabodenoson 6.0% / latanoprost 0.005% QD
Trabodenoson 6.0% / latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.
DRUGtrabodenoson 3.0% / latanoprost 0.005% QD
Trabodenoson 3.0% / latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.
DRUGtrabodenoson 6.0% / latanoprost 0.0025% QD
Trabodenoson 6.0% / latanoprost 0.0025% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.
DRUGlatanoprost 0.005% QD
Latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.
DRUGlatanoprost 0.0025% QD
Latanoprost 0.0025% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.
Sponsors
Inotek Pharmaceuticals Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of ocular hypertension (OHT) or primary open-angle glaucoma (POAG) * Mean Intraocular pressure (IOP) of ≥25 and ≤34
Exclusion criteria
* Significant visual field loss or any new field loss within the past year * Cup-to-disc ratio \>0.8 * Central corneal thickness \<490 µm or \>610 µm * A recent (acute) or chronic medical condition that might obfuscate the Subject's study data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Intraocular Pressure (IOP) | Two Months | Daily change from diurnal baseline in IOP |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Parameters, Including Treatment Emergent Adverse Events, to Assess Tolerability and Safety. | Through Study Completion, up to 9 weeks. | Collection of safety parameters, including treatment emergent adverse events, laboratory assessments, to assess tolerability and safety. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trabodenoson 6.0% / Latanoprost 0.005% QD trabodenoson 6.0% / latanoprost 0.005% Fixed-Dose Combination
trabodenoson 6.0% / latanoprost 0.005% QD: Trabodenoson 6.0% / latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks. | 39 |
| Trabodenoson 3.0% / Latanoprost 0.005% QD trabodenoson 3.0% / latanoprost 0.005% Fixed-Dose Combination
trabodenoson 3.0% / latanoprost 0.005% QD: Trabodenoson 3.0% / latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks. | 39 |
| Trabodenoson 6.0% / Latanoprost 0.0025% QD trabodenoson 6.0% / latanoprost 0.0025% Fixed-Dose Combination
trabodenoson 6.0% / latanoprost 0.0025% QD: Trabodenoson 6.0% / latanoprost 0.0025% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks. | 40 |
| Latanoprost 0.005% QD latanoprost 0.005% ophthalmic solution
latanoprost 0.005% QD: Latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks. | 41 |
| Latanoprost 0.0025% QD latanoprost 0.0025% ophthalmic solution
latanoprost 0.0025% QD: Latanoprost 0.0025% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks. | 42 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Trabodenoson 6.0% / Latanoprost 0.005% QD | Trabodenoson 3.0% / Latanoprost 0.005% QD | Trabodenoson 6.0% / Latanoprost 0.0025% QD | Latanoprost 0.005% QD | Latanoprost 0.0025% QD | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 12.08 | 64.4 years STANDARD_DEVIATION 9.18 | 68.8 years STANDARD_DEVIATION 8.43 | 66.5 years STANDARD_DEVIATION 9.84 | 66.4 years STANDARD_DEVIATION 8.57 | 66.0 years STANDARD_DEVIATION 9.74 |
| Baseline IOP | 27.67 mm of mercury STANDARD_DEVIATION 2.329 | 27.17 mm of mercury STANDARD_DEVIATION 2.278 | 27.28 mm of mercury STANDARD_DEVIATION 2.155 | 27.48 mm of mercury STANDARD_DEVIATION 2.627 | 27.31 mm of mercury STANDARD_DEVIATION 2.276 | 27.38 mm of mercury STANDARD_DEVIATION 2.323 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 9 Participants | 8 Participants | 9 Participants | 10 Participants | 44 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 27 Participants | 31 Participants | 32 Participants | 32 Participants | 152 Participants |
| Region of Enrollment United States | 39 participants | 39 participants | 40 participants | 41 participants | 42 participants | 201 participants |
| Sex: Female, Male Female | 17 Participants | 23 Participants | 19 Participants | 22 Participants | 27 Participants | 108 Participants |
| Sex: Female, Male Male | 22 Participants | 16 Participants | 21 Participants | 19 Participants | 15 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 39 | 0 / 40 | 0 / 41 | 0 / 42 |
| other Total, other adverse events | 9 / 39 | 5 / 39 | 6 / 40 | 3 / 41 | 5 / 42 |
| serious Total, serious adverse events | 0 / 39 | 0 / 39 | 0 / 40 | 0 / 41 | 0 / 42 |
Outcome results
Primary
Mean Intraocular Pressure (IOP)
Daily change from diurnal baseline in IOP
Time frame: Two Months
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trabodenoson 6.0% / Latanoprost 0.005% QD | Mean Intraocular Pressure (IOP) | -6.4 mm of mercury | Standard Error 0.48 |
| Trabodenoson 3.0% / Latanoprost 0.005% QD | Mean Intraocular Pressure (IOP) | -6.8 mm of mercury | Standard Error 0.56 |
| Trabodenoson 6.0% / Latanoprost 0.0025% QD | Mean Intraocular Pressure (IOP) | -6.4 mm of mercury | Standard Error 0.56 |
| Latanoprost 0.005% QD | Mean Intraocular Pressure (IOP) | -7.1 mm of mercury | Standard Error 0.46 |
| Latanoprost 0.0025% QD | Mean Intraocular Pressure (IOP) | -5.9 mm of mercury | Standard Error 0.53 |
Other Pre-specified
Safety Parameters, Including Treatment Emergent Adverse Events, to Assess Tolerability and Safety.
Collection of safety parameters, including treatment emergent adverse events, laboratory assessments, to assess tolerability and safety.
Time frame: Through Study Completion, up to 9 weeks.