Presbyopia
Conditions
Brief summary
This study will identify the optimum concentrations of AGN-199201 and AGN-190584 when dosed in combination once a day for the improvement of uncorrected near visual acuity in participants with presbyopia (inability to focus on items close-up).
Interventions
1 drop of AGN-199201 ophthalmic solution Doses A, B, C in the eye.
1 drop AGN-190584 ophthalmic solution doses A, B and C in the eye.
Vehicle to AGN-190584
DRUGAGN-199201 + AGN-190584 Combination
1 drop AGN-199201 and AGN-190584 fixed combination ophthalmic solution in the eye.
Vehicle to AGN-199201
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
-Normal vision at distance, either natural or post corneal laser refractive surgery, with presbyopia in each eye and complaints of poor near vision that impacts activities of daily living.
Exclusion criteria
* Use of any topical ophthalmic medications, including artificial tears other than the study medications during the study * Corneal abnormalities in either eye that interfere with visual acuity * History of cataract surgery, phakic intraocular lens surgery, corneal inlay surgery or any intraocular surgery * Diagnosis of glaucoma or ocular hypertension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | Baseline, Between hour 1 and hour 10 of each of the five 2-day dosing periods | UNVA is assessed without corrective lenses in the non-dominant eye. UNVA is measured using an eye chart and is reported as the number of lines read correctly. The lower the number of lines read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of lines read correctly means that vision has improved. |
Countries
United States
Participant flow
Pre-assignment details
Randomization and treatment assignment were based on a randomization scheme prepared by Allergan Biostatistics prior to the start of the study.
Participants by arm
| Arm | Count |
|---|---|
| AGN-190584 Vehicle and AGN-199201 Participants will receive 5 different treatments as per protocol for 2 days each. Treatment 1: nondominant eye--1 drop AGN-199201 vehicle followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle; Treatment 2: nondominant eye--1 drop AGN-199201 Lower Dose followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle; Treatment 3: nondominant eye--1 drop AGN-199201 Medium Dose followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle; Treatment 4: nondominant eye--1 drop AGN-199201 Higher Dose followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle; Treatment 5: nondominant eye--1 drop fixed combination of AGN-199201 and AGN-190584 followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle. | 41 |
| AGN-190584 Lower Dose and AGN-199201 Participants will receive 5 different treatments as per protocol for 2 days each. Treatment 1: nondominant eye--1 drop AGN-199201 vehicle followed by 1 drop AGN-190584 Lower Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 2: nondominant eye--1 drop AGN-199201 Lower Dose followed by 1 drop AGN-190584 Lower Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 3: nondominant eye--1 drop AGN-199201 Medium Dose followed by 1 drop AGN-190584 Lower Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 4: nondominant eye--1 drop AGN-199201 Higher Dose followed by 1 drop AGN-190584 Lower Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 5: nondominant eye--1 drop fixed combination of AGN-199201 and AGN-190584 followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle. | 39 |
| AGN-190584 Medium Dose and AGN-199201 Participants will receive 5 different treatments as per protocol for 2 days each. Treatment 1: nondominant eye--1 drop AGN-199201 vehicle followed by 1 drop AGN-190584 Medium Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 2: nondominant eye--1 drop AGN-199201 Lower Dose followed by 1 drop AGN-190584 Medium Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 3: nondominant eye--1 drop AGN-199201 Medium Dose followed by 1 drop AGN-190584 Medium Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 4: nondominant eye--1 drop AGN-199201 Higher Dose followed by 1 drop AGN-190584 Medium Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 5: nondominant eye--1 drop fixed combination of AGN-199201 and AGN-190584 followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle. | 42 |
| AGN-190584 Higher Dose and AGN-199201 Participants will receive 5 different treatments as per protocol for 2 days each. Treatment 1: nondominant eye--1 drop AGN-199201 vehicle followed by 1 drop AGN-190584 Higher Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 2: nondominant eye--1 drop AGN-199201 Lower Dose followed by 1 drop AGN-190584 Higher Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 3: nondominant eye--1 drop AGN-199201 Medium Dose followed by 1 drop AGN-190584 Higher Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 4: nondominant eye--1 drop AGN-199201 Higher Dose followed by 1 drop AGN-190584 Higher Dose, dominant eye--2 drops AGN-190584 vehicle; Treatment 5: nondominant eye--1 drop fixed combination of AGN-199201 and AGN-190584 followed by 1 drop AGN-190584 vehicle, dominant eye--2 drops AGN-190584 vehicle. | 39 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | AGN-190584 Lower Dose and AGN-199201 | AGN-190584 Medium Dose and AGN-199201 | AGN-190584 Higher Dose and AGN-199201 | AGN-190584 Vehicle and AGN-199201 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.1 Years STANDARD_DEVIATION 2.7 | 46.8 Years STANDARD_DEVIATION 2.8 | 46.7 Years STANDARD_DEVIATION 2.3 | 46.6 Years STANDARD_DEVIATION 2.9 | 46.8 Years STANDARD_DEVIATION 2.6 |
| Baseline UNVA severity ≤ 20/80 | 28 Participants | 28 Participants | 26 Participants | 26 Participants | 108 Participants |
| Baseline UNVA severity > 20/80 | 11 Participants | 14 Participants | 13 Participants | 15 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 3 Participants | 9 Participants | 7 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 39 Participants | 30 Participants | 34 Participants | 131 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 13 Participants | 3 Participants | 6 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 30 Participants | 28 Participants | 36 Participants | 32 Participants | 126 Participants |
| Sex: Female, Male Female | 27 Participants | 29 Participants | 24 Participants | 32 Participants | 112 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 15 Participants | 9 Participants | 49 Participants |
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 / 41 | 0 / 39 | 0 / 42 | 0 / 39 |
| other Total, other adverse events | 9 / 41 | 9 / 39 | 16 / 42 | 17 / 39 |
| serious Total, serious adverse events | 1 / 41 | 1 / 39 | 0 / 42 | 1 / 39 |
Outcome results
Primary
Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters
UNVA is assessed without corrective lenses in the non-dominant eye. UNVA is measured using an eye chart and is reported as the number of lines read correctly. The lower the number of lines read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of lines read correctly means that vision has improved.
Time frame: Baseline, Between hour 1 and hour 10 of each of the five 2-day dosing periods
Population: Modified Intent-to-Treat (mITT) population: all randomized patients who were randomized with a baseline and at least 1 post baseline assessment of mesopic, high contrast, UNVA.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AGN-190584 Vehicle | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Vehicle | 1.12 letters correctly read | Standard Error 0.48 |
| AGN-190584 Vehicle | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Lower Dose | 1.24 letters correctly read | Standard Error 0.44 |
| AGN-190584 Vehicle | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Medium Dose | 1.47 letters correctly read | Standard Error 0.47 |
| AGN-190584 Vehicle | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Higher Dose | 1.34 letters correctly read | Standard Error 0.55 |
| AGN-190584 Lower Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Lower Dose | 3.94 letters correctly read | Standard Error 0.34 |
| AGN-190584 Lower Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Medium Dose | 4.16 letters correctly read | Standard Error 0.39 |
| AGN-190584 Lower Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Higher Dose | 3.99 letters correctly read | Standard Error 0.41 |
| AGN-190584 Lower Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Vehicle | 3.83 letters correctly read | Standard Error 0.37 |
| AGN-190584 Medium Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Medium Dose | 5.56 letters correctly read | Standard Error 0.39 |
| AGN-190584 Medium Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Lower Dose | 5.37 letters correctly read | Standard Error 0.34 |
| AGN-190584 Medium Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Higher Dose | 5.36 letters correctly read | Standard Error 0.4 |
| AGN-190584 Medium Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Vehicle | 5.26 letters correctly read | Standard Error 0.37 |
| AGN-190584 Higher Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Higher Dose | 5.46 letters correctly read | Standard Error 0.56 |
| AGN-190584 Higher Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Lower Dose | 5.52 letters correctly read | Standard Error 0.46 |
| AGN-190584 Higher Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Vehicle | 5.42 letters correctly read | Standard Error 0.5 |
| AGN-190584 Higher Dose | Weighted Average Change From Baseline in Mesopic, High Contrast Uncorrected Near Visual Acuity (UNVA) Letters | AGN-199201 Medium Dose | 5.70 letters correctly read | Standard Error 0.48 |
Comparison: AGN-190584 Quadraticp-value: 0.0029Mixed model for repeated measures
Comparison: AGN-190584 Linearp-value: <0.0001Mixed model for repeated measures
Comparison: AGN-199201 Quadraticp-value: 0.4126Mixed model for repeated measures
Comparison: AGN-199201 Linearp-value: 0.3752Mixed model for repeated measures