A Phase 3 Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia (GEMINI 2)

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

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.

Study Overview

• Status: Completed
• Conditions: Presbyopia
• Intervention / Treatment: Other: Vehicle; Drug: Pilocarpine HCl Ophthalmic Solution

• Study Type: Interventional
• Enrollment (Actual): 427
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36301
      • Eye Center South
  • Arizona
    • Prescott, Arizona, United States, 86301
      • M&M Eye Institute
    • Sun City, Arizona, United States, 85351
      • Walman Eye Center
  • California
    • Azusa, California, United States, 91702
      • Milton M. Hom, OD, FAAO
    • Glendale, California, United States, 91204
      • Global Research Management
    • Los Angeles, California, United States, 90067
      • Advanced Vision Care
    • Mission Hills, California, United States, 91345
      • North Valley Eye Medical Group, Inc.
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
  • Colorado
    • Littleton, Colorado, United States, 80120
      • Corneal Consultants of Colorado
  • Florida
    • Crystal River, Florida, United States, 34429
      • Benjamin Knox Lambright, MD
    • Fort Lauderdale, Florida, United States, 33309
      • South Florida Vision Center
    • Jacksonville, Florida, United States, 32256
      • Bowden Eye Associates
    • Mount Dora, Florida, United States, 32757
      • Mid Florida Eye Center
    • Sebring, Florida, United States, 33870
      • Newsom Eye & Laser Center
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Clayton Eye Center
  • Illinois
    • Des Plaines, Illinois, United States, 60016
      • The Midwest Center for Sight
    • Lake Villa, Illinois, United States, 60046
      • Jacksoneye
  • Kansas
    • Pittsburg, Kansas, United States, 66762
      • Kannarr Eye Care
    • Shawnee Mission, Kansas, United States, 66204
      • Heart of America Eyecare
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Cincinnati Eye Institute
  • Minnesota
    • Bloomington, Minnesota, United States, 55420
      • Chu Laser Eye Institute
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • Moyes Eye Center
    • Kansas City, Missouri, United States, 64133
      • Silverstein Eye Centers
    • Saint Louis, Missouri, United States, 63128
      • Tekwani Vision Center
  • Nevada
    • Las Vegas, Nevada, United States, 89117
      • Amel Youssef, OD
    • Las Vegas, Nevada, United States, 89128
      • Debry Medical Services PC
  • Pennsylvania
    • Wilkes-Barre, Pennsylvania, United States, 18702
      • Bucci Laser Vision
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Waring Vision Institute
  • Tennessee
    • Maryville, Tennessee, United States, 37803
      • University Eye Surgeons
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care, PA
  • Texas
    • Austin, Texas, United States, 78731
      • Keystone Research ltd. at Texan Eye
    • El Paso, Texas, United States, 79902
      • The Cataract and Glaucoma Center
    • Hurst, Texas, United States, 76054
      • Texas Eye & Laser Ctr
  • Utah
    • Ogden, Utah, United States, 84403
      • Benjamin Travis Dastrup, MD
  • Virginia
    • Falls Church, Virginia, United States, 22046
      • Vision Consultants and Surgeons

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vehicle; Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Other: Vehicle; Vehicle, one drop in each eye, once daily, for up to 30 days.
Experimental: Pilocarpine HCl Ophthalmic Solution; 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; Pilocarpine HCl ophthalmic solution 1.25%, one drop in each eye, once daily, for up to 30 days.; Other Names: AGN-190584; VUITY

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Allergan

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): September 10, 2020
• Study Completion (Actual): September 10, 2020

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: November 27, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Presbyopia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Cholinergic Agonists; Pharmaceutical Solutions; Miotics; Muscarinic Agonists; Ophthalmic Solutions; Pilocarpine
• Other Study ID Numbers: 1883-302-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Allergan will share de-identified patient-level data and study-level data including protocols and clinical study reports for phase 2 - 4 trials completed after 2008 that are registered to ClinicalTrials.gov or EudraCT, have received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published. To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes. More information can be found on http://www.allerganclinicaltrials.com/.
• IPD Sharing Time Frame: After having received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published.
• IPD Sharing Access Criteria: To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes.
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No