Glaucoma, Open-Angle, Hypertension, Ocular
Conditions
Brief summary
The objective of this clinical study is to evaluate the safety and efficacy of NCX 470 ophthalmic solution in lowering intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. Three different concentrations of NCX 470 ophthalmic solution (0.021%, 0.042%, and 0.065%) will be compared to latanoprost 0.005% ophthalmic solution.
Interventions
DRUGNCX 470
NCX 470 Ophthalmic Solution
Latanoprost 0.005% Ophthalmic Solution
Sponsors
Nicox Ophthalmics, Inc.
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 85 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of open-angle glaucoma or ocular hypertension in both eyes * Qualifying IOP at 3 time points throughout the day at 2 visits following washout of IOP-lowering medication, if applicable * Qualifying best-corrected visual acuity (BCVA) using the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol in each eye * Ability to provide informed consent and follow study instructions
Exclusion criteria
* Pigmentary or pseudoexfoliative glaucoma * Narrow anterior chamber angles or disqualifying corneal thickness in either eye * Clinically significant ocular disease in either eye * Previous complicated surgery or certain types of glaucoma surgery in either eye * Incisional ocular surgery or severe trauma in either eye within the past 6 months * Uncontrolled systemic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Study Eye Mean Diurnal IOP at the Week 4 | Baseline, Week 4 | Participants used medication in both eyes for 4 weeks with one eye was designated the study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or the right eye if both eyes had the same IOP value at baseline). Mean diurnal IOP at week 4 is the average of the 8AM, 10AM and 4PM IOPs at week 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Baseline, week 1, week 2, exit visit | Participants used medication in both eyes from baseline to the evening prior to the week 4 visit. One eye was designated the study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or the right eye if both eyes had the same IOP value at baseline). Mean diurnal IOP is the average of the 8AM, 10AM and 4PM values. Visits were conducted at week 1, week 2, week 4, and an exit visit (1 to 2 days following the week 4 visit) |
| Percentage of Subjects With Treatment-emergent Ocular Adverse Events | 4 weeks for adverse events and through 30 days post-treatment for serious adverse events | Safety and tolerability based on percentage of subjects with treatment-emergent ocular adverse events |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from ophthalmologists' clinics in the US. The first participant for the study was screened in August 2018 and the last participant exited the trial in August 2019.
Pre-assignment details
Potential participants were screened for eligibility and those on intraocular pressure (IOP) lowering medication were required to undergo a wash out of 5 to 42 days (dependent on the class of medication). After the appropriate washout period, or after a minimum of 5 days for participants who were not on IOP lowering medication at screening, participants underwent 2 eligibility visits held 3 to 7 days apart. Those who qualified were randomized to one of the 4 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| NCX 470 0.021% NCX 470 Ophthalmic Solution, 0.021% dosed once daily for 4 weeks
NCX 470: NCX 470 Ophthalmic Solution | 111 |
| NCX 470 0.042% NCX 470 Ophthalmic Solution, 0.042% dosed once daily for 4 weeks
NCX 470: NCX 470 Ophthalmic Solution | 108 |
| NCX 470 0.065% NCX 470 Ophthalmic Solution, 0.065% dosed once daily for 4 weeks
NCX 470: NCX 470 Ophthalmic Solution | 107 |
| Latanoprost 0.005% Latanoprost Ophthalmic Solution, 0.005% dosed once daily for 4 weeks
Latanoprost 0.005%: Latanoprost 0.005% Ophthalmic Solution | 107 |
| Total | 433 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | NCX 470 0.021% | NCX 470 0.042% | NCX 470 0.065% | Latanoprost 0.005% | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 63 Participants | 62 Participants | 54 Participants | 52 Participants | 231 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 46 Participants | 53 Participants | 55 Participants | 202 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 20 Participants | 16 Participants | 18 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 88 Participants | 91 Participants | 89 Participants | 356 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 32 Participants | 32 Participants | 35 Participants | 134 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 72 Participants | 74 Participants | 71 Participants | 70 Participants | 287 Participants |
| Region of Enrollment United States | 111 Participants | 108 Participants | 107 Participants | 107 Participants | 433 Participants |
| Sex: Female, Male Female | 54 Participants | 71 Participants | 58 Participants | 57 Participants | 240 Participants |
| Sex: Female, Male Male | 57 Participants | 37 Participants | 49 Participants | 50 Participants | 193 Participants |
| Study Eye Baseline Mean Diurnal IOP (mmHg) | 26.62 mmHg STANDARD_DEVIATION 1.663 | 26.89 mmHg STANDARD_DEVIATION 1.987 | 26.80 mmHg STANDARD_DEVIATION 2.069 | 26.68 mmHg STANDARD_DEVIATION 1.745 | 26.75 mmHg STANDARD_DEVIATION 1.866 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 111 | 0 / 108 | 0 / 107 | 0 / 107 |
| other Total, other adverse events | 24 / 111 | 42 / 108 | 39 / 107 | 20 / 107 |
| serious Total, serious adverse events | 1 / 111 | 2 / 108 | 1 / 107 | 0 / 107 |
Outcome results
Primary
Change From Baseline in Study Eye Mean Diurnal IOP at the Week 4
Participants used medication in both eyes for 4 weeks with one eye was designated the study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or the right eye if both eyes had the same IOP value at baseline). Mean diurnal IOP at week 4 is the average of the 8AM, 10AM and 4PM IOPs at week 4.
Time frame: Baseline, Week 4
Population: All participants who were randomized and who had diurnal IOP values at week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NCX 470 0.021% | Change From Baseline in Study Eye Mean Diurnal IOP at the Week 4 | -7.79 mmHg | Standard Deviation 2.606 |
| NCX 470 0.042% | Change From Baseline in Study Eye Mean Diurnal IOP at the Week 4 | -8.28 mmHg | Standard Deviation 2.511 |
| NCX 470 0.065% | Change From Baseline in Study Eye Mean Diurnal IOP at the Week 4 | -8.70 mmHg | Standard Deviation 3.15 |
| Latanoprost 0.005% | Change From Baseline in Study Eye Mean Diurnal IOP at the Week 4 | -7.41 mmHg | Standard Deviation 2.666 |
Comparison: NCX 470 0.21% was compared to latanoprost.p-value: 0.266695% CI: [-1.11, 0.31]ANCOVA
Comparison: NCX 0.042% was compared to latanoprost.p-value: 0.028195% CI: [-1.52, -0.09]ANCOVA
Comparison: NCX 0.065% was compared to latanoprost.p-value: 0.000995% CI: [-1.96, -0.51]ANCOVA
Secondary
Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit
Participants used medication in both eyes from baseline to the evening prior to the week 4 visit. One eye was designated the study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or the right eye if both eyes had the same IOP value at baseline). Mean diurnal IOP is the average of the 8AM, 10AM and 4PM values. Visits were conducted at week 1, week 2, week 4, and an exit visit (1 to 2 days following the week 4 visit)
Time frame: Baseline, week 1, week 2, exit visit
Population: All participants who were randomized and who had diurnal IOP values at the week 1, week 2, exit visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NCX 470 0.021% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 1 | -7.73 mmHg | Standard Deviation 2.783 |
| NCX 470 0.021% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Exit Visit | -4.95 mmHg | Standard Deviation 3.237 |
| NCX 470 0.021% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 2 | -7.96 mmHg | Standard Deviation 2.774 |
| NCX 470 0.042% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 1 | -8.15 mmHg | Standard Deviation 2.577 |
| NCX 470 0.042% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Exit Visit | -5.59 mmHg | Standard Deviation 2.827 |
| NCX 470 0.042% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 2 | -8.38 mmHg | Standard Deviation 2.439 |
| NCX 470 0.065% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 2 | -8.87 mmHg | Standard Deviation 2.797 |
| NCX 470 0.065% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 1 | -8.66 mmHg | Standard Deviation 3.098 |
| NCX 470 0.065% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Exit Visit | -5.98 mmHg | Standard Deviation 3.019 |
| Latanoprost 0.005% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 1 | -7.54 mmHg | Standard Deviation 2.735 |
| Latanoprost 0.005% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Exit Visit | -4.89 mmHg | Standard Deviation 3.009 |
| Latanoprost 0.005% | Change From Baseline in Study Eye Mean Diurnal IOP at Week 1, Week 2, and Exit Visit | Week 2 | -7.99 mmHg | Standard Deviation 2.504 |
Comparison: NCX 470 0.021% was compared to latanoprost.p-value: <0.9788ANCOVA
Comparison: NCX 470 0.042% was compared to latanoprost.p-value: <0.3863ANCOVA
Comparison: NCX 470 0.065% was compared to latanoprost.p-value: <0.0174ANCOVA
Secondary
Percentage of Subjects With Treatment-emergent Ocular Adverse Events
Safety and tolerability based on percentage of subjects with treatment-emergent ocular adverse events
Time frame: 4 weeks for adverse events and through 30 days post-treatment for serious adverse events
Population: Safety population defined as all participants who received at least one dose of the study medication during the 4-week treatment period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NCX 470 0.021% | Percentage of Subjects With Treatment-emergent Ocular Adverse Events | 34 Participants |
| NCX 470 0.042% | Percentage of Subjects With Treatment-emergent Ocular Adverse Events | 52 Participants |
| NCX 470 0.065% | Percentage of Subjects With Treatment-emergent Ocular Adverse Events | 50 Participants |
| Latanoprost 0.005% | Percentage of Subjects With Treatment-emergent Ocular Adverse Events | 21 Participants |