Trial Outcomes & Findings for A Phase 3 Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia (NCT NCT03857542)

NCT ID: NCT03857542

Last Updated: 2021-12-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 427 participants
• Primary outcome timeframe: Baseline (Day 1) to Day 30 (Hour 3)
• Results posted on: 2021-12-29

Participant Flow

Distance-corrected near visual acuity (DCNVA) measurements at 1 site were not conducted correctly at the screening and baseline visits; all participants from this site were excluded from efficacy analyses.

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	215	212
Overall Study COMPLETED	209	207
Overall Study NOT COMPLETED	6	5

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	1	3
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	2	1
Overall Study Reason not Specified	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Vehicle n=215 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=212 Participants Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.	Total n=427 Participants Total of all reporting groups
Age, Continuous	49.9 years STANDARD_DEVIATION 3.48 • n=5 Participants	49.6 years STANDARD_DEVIATION 3.71 • n=7 Participants	49.8 years STANDARD_DEVIATION 3.60 • n=5 Participants
Sex: Female, Male Female	162 Participants n=5 Participants	138 Participants n=7 Participants	300 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	74 Participants n=7 Participants	127 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	41 Participants n=5 Participants	37 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	174 Participants n=5 Participants	175 Participants n=7 Participants	349 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	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	5 Participants n=7 Participants	13 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	29 Participants n=5 Participants	35 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) White	176 Participants n=5 Participants	171 Participants n=7 Participants	347 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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: ITT Population included all randomized participants. Missing data was imputed as non-responders; excluding data from 1 site.

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.

Outcome measures

Measure	Vehicle n=203 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=196 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, Without Losing More Than 5 Letters of Mesopic, High-Contrast, Binocular CDVA With the Same Refractive Correction at Day 30, Hour 3	10.8 percentage of participants	26.0 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; excluding data from 1 site.

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.

Outcome measures

Measure	Vehicle n=203 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=196 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 6	9.9 percentage of participants	16.3 percentage of participants

SECONDARY outcome

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

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis at Baseline and timepoint; excluding data from 1 site.

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.

Outcome measures

Measure	Vehicle n=197 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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	8.6 percentage of participants	14.5 percentage of participants

SECONDARY outcome

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

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis; excluding data from 1 site.

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.

Outcome measures

Measure	Vehicle n=197 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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	4.7 letters read correctly Standard Error 0.44	8.8 letters read correctly Standard Error 0.44

SECONDARY outcome

Timeframe: Day 30 (Hour 1)

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis; excluding data for 1 site.

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.

Outcome measures

Measure	Vehicle n=198 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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	82.8 percentage of participants	92.7 percentage of participants

SECONDARY outcome

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

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis; excluding data for 1 site. ANCOVA was used for the analysis.

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).

Outcome measures

Measure	Vehicle n=197 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=192 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	0.5 score on a scale Standard Error 0.09	1.3 score on a scale Standard Error 0.09

SECONDARY outcome

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

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis; excluding data from 1 site.

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.

Outcome measures

Measure	Vehicle n=198 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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	2.9 number of letters read correctly Standard Error 0.38	6.4 number of letters read correctly Standard Error 0.39

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 30 (Hour 10)

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis at Baseline and timepoint; excluding data from 1 site.

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.

Outcome measures

Measure	Vehicle n=195 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=191 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	8.7 percentage of participants	12.6 percentage of participants

SECONDARY outcome

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

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis; excluding data from 1 site.

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.

Outcome measures

Measure	Vehicle n=196 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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	3.9 letters read correctly Standard Error 0.41	6.5 letters read correctly Standard Error 0.41

SECONDARY outcome

Timeframe: Day 30 (Hour 3)

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

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.

Outcome measures

Measure	Vehicle n=198 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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	77.8 percentage of participants	90.2 percentage of participants

SECONDARY outcome

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

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

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.

Outcome measures

Measure	Vehicle n=197 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=192 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	0.5 score on a scale Standard Error 0.08	1.2 score on a scale Standard Error 0.08

SECONDARY outcome

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

Population: ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available for analysis. ANCOVA was used for the 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=197 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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 Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3	-0.5 score on a scale Standard Error 0.06	-0.9 score on a scale Standard Error 0.06

SECONDARY outcome

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

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

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.

Outcome measures

Measure	Vehicle n=197 Participants Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=193 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: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Pilocarpine HCl Ophthalmic Solution

Serious events: 0 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vehicle n=215 participants at risk Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=212 participants at risk Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
Gastrointestinal disorders Dysphagia	0.47% 1/215 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)	0.00% 0/212 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)
Nervous system disorders Guillain-Barre syndrome	0.47% 1/215 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)	0.00% 0/212 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)

Other adverse events

Measure	Vehicle n=215 participants at risk Participants received one drop of vehicle in each eye, once daily, for up to 30 days.	Pilocarpine HCl Ophthalmic Solution n=212 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	5.1% 11/215 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)	15.6% 33/212 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)
Eye disorders Conjunctival hyperaemia	5.1% 11/215 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)	7.1% 15/212 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)
Eye disorders Vision blurred	0.47% 1/215 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)	6.1% 13/212 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)
Eye disorders Eye pain	1.4% 3/215 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)	5.7% 12/212 • First dose of study drug intervention to within 30 days after last dose (Up to 60 days)

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