Presbyopia
Conditions
Brief summary
Safety and efficacy of POS in participants with presbyopia
Detailed description
Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Study of the Efficacy and Safety of Phentolamine Ophthalmic Solution (POS) 0.75% in Participants with Presbyopia
Interventions
Once daily dosing
DRUGPlacebo
Once daily dosing
Sponsors
Ocuphire Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double-masked, placebo-controlled
Intervention model description
Parallel assignment
Eligibility
Sex/Gender
ALL
Age
45 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
Participants must meet all of the following criteria: 1. Males or females ≥ 45 and ≤ 64 years of age 2. Able to comply with all protocol-mandated procedures independently and to attend all scheduled office visits 3. Able and willing to give signed informed consent 4. Able to self-administer study medication throughout the study period Inclusion criteria #5, #6, and #7 must all be met at both Screening and Baseline Visits: 5. BCDVA of 55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/20 Snellen equivalent) or better in photopic conditions in each eye 6. DCNVA of 50 ETDRS letters (20/50 Snellen equivalent) or worse but not \<35 ETDRS letters (20/100 Snellen equivalent) in photopic conditions in each eye and binocularly 7. For participants who depend on reading glasses or bifocals, binocular best-corrected near VA of 65 ETDRS letters (20/25 Snellen equivalent) or better 8. Photopic PD of ≥ 4 mm in the study eye at Screening
Exclusion criteria
Excluded from the study will be individuals with any of the following characteristics: Ophthalmic (in either eye): 1. Use of any topical prescription (including Vuity® or Qlosi™) or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of Screening until study completion, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.) and artificial tears as specified in Exclusion Criterion #2 below 2. Use of any OTC artificial tears (preserved or unpreserved) during visit days or 15 min before or after instillation of study medication 3. Use of Ryzumvi™ (POS) within 7 days prior to Screening 4. Use of any dry eye product, such as topical ophthalmic therapy for dry eye (eg, generic cyclosporine, Restasis®, Xiidra®, Cequa®, Eysuvis®, and Meibo®) or intranasal dry eye product (eg, Tyrvaya®) or other devices within 12 months prior to Screening 5. Tear break-up time of \< 5 seconds or corneal fluorescein staining (CFS) Grade ≥ 2 in the inferior zone or Grade ≥ 1 in the central zone using the National Eye Institute scale 6. Clinically significant ocular disease (eg, cataract, glaucoma, corneal edema, uveitis, retinal degeneration, loss of visual field, or any macular pathology) that, in the judgment of the Investigator, might interfere with study procedures 7. Recent or current evidence of ocular infection or inflammation in either eye (such as current evidence of clinically significant blepharitis, conjunctivitis, keratitis, etc.). Participants must be symptom free for at least 7 days prior to Screening 8. Any history of herpes simplex or herpes zoster keratitis 9. Known allergy, hypersensitivity, or contraindication to any component of the phentolamine or vehicle formulations 10. Prior participation in a study involving the use of POS for the treatment of presbyopia or night vision disturbance 11. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal 12. Ocular trauma within 6 months prior to Screening 13. Ocular surgery or any ocular laser treatment within 6 months prior to Screening. Any history of radial keratotomy is prohibited 14. Participants with surgical monovision, multifocal, or extended depth-of-focus intraocular lenses (IOLs). Monofocal IOLs are acceptable if in place \> 6 months prior to Screening 15. Monofocal IOL in place \> 6 months prior to Screening with any posterior capsule opacification 16. History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris (eg, irregularly shaped pupil, neurogenic pupil disorder, iris atrophy, iridotomy, iridectomy, iritis, etc.) 17. Unwilling or unable to discontinue use of contact lenses at least 1 hour prior to Screening for soft contact lenses or at least 8 hours prior to Screening for hard gas permeable contact lenses, and at least 8 hours (for both types of lenses) prior to all other office visits Systemic: 18. Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists (eg, chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure (BP) or heart rate (HR); second- or third-degree heart blockage or congestive heart failure) 19. Known hypersensitivity or contraindication to any systemic cholinergic parasympathomimetic agent 20. Clinically significant systemic disease (eg, uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere with the study as deemed by the judgment of the Investigator 21. Initiation of treatment with, or any changes to, the current dosage, drug, or regimen of any systemic adrenergic or cholinergic drugs within 7 days prior to Screening or during the study; however, Flomax® (tamsulosin) is specifically excluded 22. Participation in any investigational study within 30 days prior to Screening 23. Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Acceptable methods include the use of at least one of the following: intrauterine device, hormonal contraception (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence. A female is considered to be of childbearing potential unless she is 1 year postmenopausal or 3 months post-surgical sterilization. All females of childbearing potential, including those with post-tubal ligation, must have a negative urine pregnancy test result at Visit 1 (Screening) 24. Resting HR outside the range of 50 to 110 beats per min (bpm) following at least a 5 min rest period in the sitting position at Visit 1 (Screening). HR may be repeated only once if outside the specified range, following another 5 min rest period in the sitting position 25. Hypertension with resting diastolic BP \> 105 mmHg or systolic BP \> 160 mmHg following at least a 5-min rest period in the sitting position at Visit 1 (Screening). BP may be repeated only once if outside the specified range, following another 5-min rest period in the sitting position
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With ≥ 15 Letters of Improvement in Binocular DCNVA and With < 5 Letters of Loss in Binocular BCDVA From Baseline Comparing POS-treated Participants to Placebo-treated Participants at 12 Hours Post-dose at Visit 4 (Day 8) | 8 Days | The primary efficacy endpoint is the percentage of participants with ≥ 15 letters of improvement in binocular DCNVA and with \< 5 letters of loss in binocular BCDVA from baseline comparing POS-treated participants to placebo-treated participants at 12 hours post-dose at Visit 4 (Day 8). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With ≥ 15 Letters of Improvement in Binocular DCNVA and With < 5 Letters of Loss in Binocular BCDVA From Baseline at Day 1 (1-hour Post-dose), Day 3, and Week 6 | 6 Weeks | This secondary efficacy endpoint is the percentage of participants with ≥ 15 letters of improvement in binocular DCNVA and with \< 5 letters of loss in binocular BCDVA from baseline comparing POS-treated participants to placebo-treated participants at 12 hours post-dose at Day 1 (1-hour post-dose), Day 3, and Week 6. |
| Percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in DCNVA From Baseline (Binocular) at Day 1 (0.5 Hours and 1 Hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | The percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in DCNVA From Baseline (Monocular and Binocular) at Day 1 (0.5 hours and 1 hour post-dose), Day 3, Day 8, and Week 6. |
| Percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in DCNVA From Baseline (Monocular - Study Eye) at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in DCNVA from baseline (monocular - study eye) at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6. |
| Change in DCNVA From Baseline (Binocular) at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the change in DCNVA from baseline (binocular) at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6. |
| Change in DCNVA From Baseline (Monocular - Study Eye) at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the Change in DCNVA From Baseline (Monocular - Study Eye) at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6 |
| Change in Mean Binocular DCNVA From Baseline at Week 6 Compared to the Best Prior Observed Change From Baseline in Mean Binocular DCNVA in Subjects Treated With POS | 6 Weeks | This outcome measure investigates the change in mean binocular DCNVA from baseline at Week 6 compared to the best prior observed change from baseline in mean binocular DCNVA in subjects treated with POS. |
| Percentage of Subjects With DCNVA ≤ 20/15, ≤ 20/20, ≤ 20/25, ≤ 20/32, ≤ 20/40, ≤ 20/50, ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the percentage of subjects with DCNVA ≤ 20/15, ≤ 20/20, ≤ 20/25, ≤ 20/32, ≤ 20/40, ≤ 20/50, ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6. |
| Percentage of Subjects With Baseline DCNVA ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 With a ≥ 10-Letter and ≥ 15-Letter Improvement in DCNVA at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the percentage of subjects with baseline DCNVA ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 with a ≥ 10-Letter and ≥ 15-Letter Improvement in DCNVA at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6. |
| Percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in Binocular DCIVA From Baseline at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in binocular DCIVA from baseline at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6. |
| Change in Binocular DCIVA From Baseline at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the change in binocular DCIVA from baseline at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6. |
| Percentage of Subjects With Loss or Improvement in BCDVA From Baseline (Binocular) at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the percentage of subjects with loss or improvement in BCDVA from baseline (Binocular) at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6. |
| Change in BCDVA From Baseline (Binocular) at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the change in BCDVA from baseline (Binocular) at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6. |
| Change in BCDVA From Baseline (Monocular - Study Eye) at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure will investigate the Change in BCDVA From Baseline (Monocular - Study Eye) at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6. |
| Change in Pupil Diameter From Baseline at Day 3 and Day 8 | 8 Days | This outcome measure will investigate the change in pupil diameter from baseline at Day 3 and Day 8. |
| Percent Change in Pupil Diameter From Baseline at Day 3 & Day 8 | 8 Days | This outcome measure will investigate the Percent Change in Pupil Diameter from Baseline at Day 3 \& Day 8. |
| Percentage of Subjects With Pupil Diameter of < 3.5, < 3.0, < 2.5, < 2.0, and < 1.5 mm at Day 3 and Day 8 | 8 Days | This outcome measure will investigate the percentage of subjects with pupil diameter of \< 3.5, \< 3.0, \< 2.5, \< 2.0, and \< 1.5 mm at Day 3 and Day 8. |
| Percentage of Subjects With Pupil Diameter of 1.5 to < 2.0 mm, 2.0 to < 2.5 mm, 2.5 to < 3.0 mm, and 3.0 to < 3.5 mm at Day 3 and Day 8 | 8 Days | This outcome measure will investigate the percentage of subjects with pupil diameter of 1.5 to \< 2.0 mm, 2.0 to \< 2.5 mm, 2.5 to \< 3.0 mm, and 3.0 to \< 3.5 mm at Day 3 and Day 8. |
| Change From Baseline in Overall and Component Subject-Reported Outcomes at Day 3, Day 8, and Week 6 | 6 Weeks | This outcome measure investigates the change from baseline in overall and component subject-reported outcomes at Day 3, Day 8, and Week 6. : Responses to each question used a 1-5 scale with 1=Worst outcome and 5=Best outcome. |
Countries
United States
Contacts
STUDY_CHAIRJay V Pepose, MD
Ocuphire Pharma
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54.3 Years STANDARD_DEVIATION 5.08 |
| BCDVA Binocular | 59.7 Letters STANDARD_DEVIATION 3.74 |
| BCDVA in the Fellow Eye | 57.8 Letters STANDARD_DEVIATION 3 |
| BCDVA in the Study Eye | 58.1 Letters STANDARD_DEVIATION 3.36 |
| DCIVA Binocular | 50.9 Letters STANDARD_DEVIATION 5.71 |
| DCIVA in the Fellow Eye | 48.4 Letters STANDARD_DEVIATION 6.19 |
| DCIVA in the Study Eye | 47.1 Letters STANDARD_DEVIATION 5.94 |
| DCNVA Binocular | 46.9 Letters STANDARD_DEVIATION 3.96 |
| DCNVA in the Fellow Eye | 45.9 Letters STANDARD_DEVIATION 4.11 |
| DCNVA in the Study Eye | 43.1 Letters STANDARD_DEVIATION 4.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 293 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| IOP in the Fellow Eye | 14.6 mmHg STANDARD_DEVIATION 2.58 |
| IOP in the Study Eye | 14.6 mmHg STANDARD_DEVIATION 2.59 |
| Irides Type Dark | 316 Participants |
| Irides Type Light | 253 Participants |
| PD in Fellow Eye | 4.787 millimeters STANDARD_DEVIATION 0.677 |
| PD in Study Eye | 4.737 millimeters STANDARD_DEVIATION 0.675 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants |
| Race (NIH/OMB) More than one race | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 191 Participants |
| Sex: Female, Male Female | 229 Participants |
| Sex: Female, Male Male | 80 Participants |
| Study Eye OD | 223 Participants |
| Study Eye OS | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 341 | 0 / 228 |
| other Total, other adverse events | 158 / 341 | 21 / 228 |
| serious Total, serious adverse events | 4 / 341 | 3 / 228 |
Outcome results
None listed