Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia (GEMINI 1)

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

A study to evaluate the efficacy, safety, and pharmacokinetics of pilocarpine hydrochloride (HCl) ophthalmic solution (AGN-190584) when administered bilaterally, once daily for 30 days in participants with presbyopia.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 323
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Eye Center
    • Scottsdale, Arizona, United States, 85260
      • Schwartz Laser Eye Center
  • California
    • Beverly Hills, California, United States, 90210
      • Assil Eye Institute
    • Los Angeles, California, United States, 90017
      • American Institute of Research
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
    • Rancho Cordova, California, United States, 95670
      • Martel Eye Medical Group
    • Sacramento, California, United States, 95815
      • Grutzmacher & Lewis, A Medical Corporation DBA Sacramento Eye Consultants
  • Colorado
    • Colorado Springs, Colorado, United States, 80919
      • Haas Vision Center
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Danbury Eye Physicians and Surgeons P.C.
  • Florida
    • Bradenton, Florida, United States, 34209
      • The Eye Associates
    • Delray Beach, Florida, United States, 33484
      • Bruce Segal, MD
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Research Center
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Tampa, Florida, United States, 33612
      • USF Eye Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Price Vision Group
  • Kansas
    • Leawood, Kansas, United States, 66211
      • Sabates Eye Centers
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • The Eye Care Institute
  • Maryland
    • Havre De Grace, Maryland, United States, 21078
      • Seidenberg Protzko Eye Associates
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Tauber Eye Center
  • New York
    • Poughkeepsie, New York, United States, 12603
      • Alterman, Modi & Wolter
    • Rochester, New York, United States, 14618
      • Rochester Ophthalmological Group, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Mundorf Eye Center
  • Ohio
    • Columbus, Ohio, United States, 43212
      • The Ohio State University
    • Powell, Ohio, United States, 43065
      • EyeCare Professionals DWA Insight Research Clinic, LLC
  • Oregon
    • Portland, Oregon, United States, 97210
      • Devers Eye Institute
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Scott & Christie and Associates, PC
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
    • Sioux Falls, South Dakota, United States, 57108
      • Vance Thompson Vision
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Southern College of Optometry
    • Nashville, Tennessee, United States, 37205
      • Nashville Vision Associates
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Hill Country Eye Center
    • Dallas, Texas, United States, 75243
      • Key-Whitman Eye Center
    • San Antonio, Texas, United States, 78229
      • R and R Eye Research, LLC
    • San Antonio, Texas, United States, 78229
      • PNV Clinical Research LLC
  • Utah
    • Draper, Utah, United States, 84020
      • Hoopes, Durrie, Rivera Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 55 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:

• History of cataract surgery, phakic intraocular lens surgery, corneal inlay surgery, radial keratotomy, or any intraocular surgery
• Use of any topical ophthalmic medications, including artificial tears other than the study medications during the study
• Use of temporary or permanent punctal plugs or history of punctal cautery in one or both eyes
• 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
• Diagnosis of any type of glaucoma or ocular hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• 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 Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3	Visual acuity for near (40 centimeters (cm)) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (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 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (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 candelas per square meter 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) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter 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 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 low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. Mixed effect model for repeated measures (MMRM) was used for analyses.	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. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.	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 an article in newspaper, 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, rating their vision-related reading ability 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 on performance 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. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.	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 (40cm) 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 (Day1) 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. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.	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) target was measured in mesopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.	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 an article in newspaper, 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, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close to 5=excellent; impact of squinting on performance 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,1=dissatisfied,2=neither satisfied nor dissatisfied,3=satisfied, 4=very satisfied. The score based on satisfaction items=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses) for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline=higher satisfaction.	Baseline (Day 1) to Day 30 (Hour 3)
Mean Change From Baseline in Presbyopia Impact and 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. PICQ Impact domain had 6 items: Item 9:Rely on others,15:rest eyes,16:Feel older,17:Feel self-conscious,19:Take longer to complete a task,20:Inconvenient. First 5 impacts items included response categories: 0=never to 4=all the time. Item 20 had response categories: 0=not at all to 4=extremely. Item 9 included an additional response category with a value of 9 to indicate question was not applicable to participant and the responses were assigned missing values. PICQ Impacts Score=[(Item9+Item15+Items16,17Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16,17 Testlet=(Item16+Item17)/non-missing responses to Items 16 and 17. PICQ Impact score ranges from 0 to 4; with 0=least amount of impacts to 4=greatest amount of impacts. Higher scores correspond to poorer outcomes. A negative change from Baseline=improvement.	Baseline (Day 1) to Day 30 (Hour 3)

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

General Publications

• Westheimer G. Topical Review: Pilocarpine-induced Miosis as Help for Early Presbyopes? Optom Vis Sci. 2022 Aug 1;99(8):632-634. doi: 10.1097/OPX.0000000000001924. Epub 2022 Jul 14.
• Waring GO 4th, Price FW Jr, Wirta D, McCabe C, Moshirfar M, Guo Q, Gore A, Liu H, Safyan E, Robinson MR. Safety and Efficacy of AGN-190584 in Individuals With Presbyopia: The GEMINI 1 Phase 3 Randomized Clinical Trial. JAMA Ophthalmol. 2022 Apr 1;140(4):363-371. doi: 10.1001/jamaophthalmol.2022.0059.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 21, 2018
• Primary Completion (ACTUAL): October 31, 2019
• Study Completion (ACTUAL): October 31, 2019

Study Registration Dates

• First Submitted: January 11, 2019
• First Submitted That Met QC Criteria: January 11, 2019
• First Posted (ACTUAL): January 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 28, 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: 1883-301-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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