Trial Outcomes & Findings for Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia (NCT NCT03804268)

NCT ID: NCT03804268

Last Updated: 2021-12-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 323 participants
• Primary outcome timeframe: Baseline (Day 1) to Day 30 (Hour 3)
• Results posted on: 2021-12-28

Participant Flow

Participant milestones

Measure	Vehicle Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution Participants received one drop of pilocarpine hydrochloride (HCl) ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Overall Study STARTED	160	163
Overall Study COMPLETED	153	161
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Measure	Vehicle Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution Participants received one drop of pilocarpine hydrochloride (HCl) ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Overall Study Adverse Event	2	2
Overall Study Withdrawal by Subject	2	0
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Vehicle n=160 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=163 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.	Total n=323 Participants Total of all reporting groups
Age, Continuous	49.7 years STANDARD_DEVIATION 3.23 • n=5 Participants	49.5 years STANDARD_DEVIATION 3.81 • n=7 Participants	49.6 years STANDARD_DEVIATION 3.53 • n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants	113 Participants n=7 Participants	235 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	50 Participants n=7 Participants	88 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants	31 Participants n=7 Participants	57 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	134 Participants n=5 Participants	132 Participants n=7 Participants	266 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) White	144 Participants n=5 Participants	148 Participants n=7 Participants	292 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Population: Intent-to-treat (ITT) Population included all randomized participants. Missing data was imputed as non-responders.

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.

Outcome measures

Measure	Vehicle n=160 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=163 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3	8.1 percentage of participants	30.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 6)

Population: ITT Population included all randomized participants. Missing data was imputed as non-responders.

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.

Outcome measures

Measure	Vehicle n=160 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=163 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6	8.8 percentage of participants	18.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 8)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.

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.

Outcome measures

Measure	Vehicle n=153 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=161 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8	8.5 percentage of participants	10.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 0.5)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.

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.

Outcome measures

Measure	Vehicle n=153 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=158 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5	4.2 letters read correctly Standard Error 0.55	9.3 letters read correctly Standard Error 0.54

SECONDARY outcome

Timeframe: Day 30 (Hour 1)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.

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.

Outcome measures

Measure	Vehicle n=153 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=161 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1	73.9 percentage of participants	92.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. Analysis of Covariance (ANCOVA) was used for analysis.

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).

Outcome measures

Measure	Vehicle n=148 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=154 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3	0.6 score on a scale Standard Error 0.11	1.4 score on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.

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.

Outcome measures

Measure	Vehicle n=153 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=161 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3	3.1 letters read correctly Standard Error 0.42	6.6 letters read correctly Standard Error 0.41

SECONDARY outcome

Timeframe: Baseline (Day1) to Day 30 (Hour 10)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.

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.

Outcome measures

Measure	Vehicle n=152 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=160 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10	8.6 percentage of participants	7.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 0.25)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.

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.

Outcome measures

Measure	Vehicle n=153 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=158 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25	3.7 letters correctly read Standard Error 0.50	6.3 letters correctly read Standard Error 0.49

SECONDARY outcome

Timeframe: Day 30 (Hour 3)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.

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.

Outcome measures

Measure	Vehicle n=153 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=161 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3	71.9 percentage of participants	84.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.

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.

Outcome measures

Measure	Vehicle n=148 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=154 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3	0.6 score on a scale Standard Error 0.11	1.4 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.

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.

Outcome measures

Measure	Vehicle n=148 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=159 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3	-0.5 score on a scale Standard Error 0.07	-1.0 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Population: ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.

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.

Outcome measures

Measure	Vehicle n=148 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=159 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3	-0.4 score on a scale Standard Error 0.06	-0.7 score on a scale Standard Error 0.06

Adverse Events

Vehicle

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Pilocarpine HCl Ophthalmic Solution

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vehicle n=159 participants at risk Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=163 participants at risk Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Nervous system disorders Headache	9.4% 15/159 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other (non-serious) Adverse Events: Safety Population included all participants who received at least 1 administration of study intervention.	14.1% 23/163 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other (non-serious) Adverse Events: Safety Population included all participants who received at least 1 administration of study intervention.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: clinicaltrials@allergan.com

Results disclosure agreements

• Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER