A Phase 3 Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia

Study Overview
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Brief Summary
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This clinical study will evaluate pilocarpine hydrogen chloride (HCl) ophthalmic solution (AGN-190584) in an expanded participant population to establish efficacy, safety, and tolerability versus the vehicle-control when administered, over a 30-day study intervention period, once daily bilaterally in participants with presbyopia.

Official Title
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A Phase 3, Multicenter, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of AGN-190584 in Participants With Presbyopia

Conditions
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Presbyopia

Intervention / Treatment
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* Drug: Pilocarpine HCl Ophthalmic Solution
* Other: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjective complaints of poor near vision that impact activities of daily living Exclusion Criteria Uncontrolled systemic disease Any clinical condition or previous surgery that might affect the absorption, distribution, biotransformation, or excretion of AGN-190584. History of cataract surgery, phakic intraocular lens surgery, corneal inlay surgery, radial keratotomy, or any intraocular surgery. However, participants with history of photorefractive keratectomy (PRK) or laser-assisted in situ keratomileusis (LASIK) with corrected distance visual acuity (CDVA) meeting inclusion criteria will be allowed to enroll. Known allergy or sensitivity to the study intervention or its components or other cholinergic agonist medications Concurrent use of any topical ophthalmic medications, including artificial tears, other than the study intervention during the course of the study Concurrent use of temporary or permanent punctal plugs or history of punctal cautery in one or both eyes Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study Participation in a blood or plasma donation program within 30 days prior to study intervention administration Severe dry eye disease (defined as total corneal staining ≥ grade 3 on the 5-point Oxford scale and an ocular surface disease index (OSDI) score of > 33) at the screening visit Corneal abnormalities (including keratoconus, corneal scar, Fuchs' endothelial dystrophy, guttata, or edema) in either eye that are likely to interfere with visual acuity Narrow iridocorneal angles (Shaffer grade ≤ 2 or lower on gonioscopy examination), history of angle-closure glaucoma, or previous iridotomy History of iris trauma, Adie's tonic pupil, abnormal pupil shape in either eye, or anisocoria > 1 mm between pupils under mesopic conditions at the screening visit Lens opacity in either eye that is determined to cause significant disturbance of the central visual axis on screening biomicroscopy Diagnosis of any type of glaucoma or ocular hypertension Bifocal or multifocal spectacles or contact lenses for habitual correction. Participants willing to wear study-provided monofocal correction (either spectacles or contact lenses) during the study can be enrolled Abnormal and clinically significant results according to the investigator or designee, on physical/ophthalmic examination or medical history Females who are pregnant, nursing, or planning a pregnancy during the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle<br>Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Other: Vehicle<br>* Vehicle, one drop in each eye, once daily, for up to 30 days.<br>|
| Experimental: Pilocarpine HCl Ophthalmic Solution<br>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. | Drug: Pilocarpine HCl Ophthalmic Solution<br>* Pilocarpine HCl ophthalmic solution 1.25%, one drop in each eye, once daily, for up to 30 days.<br>* Other names: VUITY;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular DCNVA, Without Losing More Than 5 Letters of Mesopic, High-Contrast, Binocular CDVA With the Same Refractive Correction at Day 30, Hour 3 | Visual acuity for near (40 centimeter (cm)) and distance (4 meter (m)) targets were measured in mesopic conditions using an eye chart. High contrast corrected distance visual acuity (CDVA) was assessed binocularly (in each eye) using the provided visual acuity charts for distance vision in a room with mesopic lighting conditions measured at the target. Forced choice letter by-letter scoring was used for each test and the total number of correct letters or the highest value (number) of the grid identified (as applicable) were recorded. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. DCNVA= distance-corrected near visual acuity. | Baseline (Day 1) to Day 30 (Hour 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular DCNVA at Day 30, Hour 6 | Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported. | Baseline (Day 1) to Day 30 (Hour 6) | 
| Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8 | Visual acuity for near (40 cm) was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. Baseline for efficacy was defined as the last non-missing efficacy assessment before the first dose of study intervention. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported. | Baseline (Day 1) to Day 30 (Hour 8) | 
| Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5 | Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as lighting 3.2 to 3.5 cd/m^2 measured at the target. Mixed effect model for repeated measures (MMRM) was used for the analysis. | Baseline (Day 1) to Day 30 (Hour 0.5) | 
| Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular DCNVA at Day 30, Hour 1 | Visual acuity for near (40 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. | Day 30 (Hour 1) | 
| Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3 | NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from a newspaper article, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rated as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent; impact of squinting as 0=No,I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes,but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. The score based on vision-related ability and impact of squinting=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses), total possible score of 0-5. Higher scores=better outcomes;positive change from Baseline=improved performance (reading ability). | Baseline (Day 1) to Day 30 (Hour 3) | 
| Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3 | Visual acuity for intermediate (66 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. MMRM was used for the analysis. | Baseline (Day 1) to Day 30 (Hour 3) | 
| Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10 | Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported. | Baseline (Day 1) to Day 30 (Hour 10) | 
| Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25 | Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. MMRM was used for the analysis. | Baseline (Day 1) to Day 30 (Hour 0.25) | 
| Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3 | Visual acuity for near (40 cm) targets was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. | Day 30 (Hour 3) | 
| Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3 | NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from a newspaper article, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, related as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent; impact of squinting as 0=No, I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes, but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. NVPTQ Satisfaction Score=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses)based on satisfaction items for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline indicates higher satisfaction. | Baseline (Day 1) to Day 30 (Hour 3) | 
| Mean Change From Baseline in Presbyopia Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3 | PICQ=20 questions about impact experienced by participants due to their problems over past 7 days.PICQ Coping domain had 8 items: 1:Normal-sized text,2:Small-sized text,3:Information on a computer,4:Information on a cell phone,5:Increase font size,6:Use glasses to read close,12:Hold reading materials farther out/closer,13:Squint to read. Each item had response categories:0=never to 4=all the time. Items 3, 4, 5, and 6 had additional response categories with values of 9/10 to indicate the question is not applicable to participant and were assigned missing values.PICQ Coping Score:(Item 1,2 Testlet+Item 3,4 Testlet+Item 5+Item 6+Item 12+Item 13)/non-missing responses to the 6 components of coping score where Items 1,2 Testlet=(Item1+Item2)/non-missing responses to Items 1,2;Items 3,4 Testlet=(Item3+Item4)/non-missing responses to Items 3, 4. Score ranges:0=to least amount of coping to 4=greatest amount of coping. Higher scores=poorer outcome; a negative change from Baseline=improvement. | Baseline (Day 1) to Day 30 (Hour 3) | 
| Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3 | PICQ had 20 questions about impact experienced by participants due to their problems seeing up over past 7 days. Impact domain of PICQ has 6 items:Item9:Rely on others,Item15:rest eyes,Item16:Feel older,Item17:Feel self-conscious,Item19:Take longer to complete task,Item20:Inconvenient.First 5 impacts items include response ranges from 0=never to 4=all of time. Item20 ranged from 0=Not at all,to 4=Extremely. Item9 included an additional response category, labeled with value of 9 to indicate question is not applicable because participant did not have opportunity to experience impact responses are assigned missing values. PICQ Impacts Score=[(Items 9+15+16&17 Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16&17 Testlet=(Items16+17)/non-missing responses to Items16 and 17. PICQ Impact score ranged 0-4, 0=least amount of impacts,4=greatest amount of impacts. Higher scores correspond to poorer outcomes; negative change from Baseline=improvement. | Baseline (Day 1) to Day 30 (Hour 3) |