GEMINI 1: Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
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:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3 [Baseline (Day 1) to 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.
Secondary Outcome Measures
- Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6 [Baseline (Day 1) to 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.
- Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8 [Baseline (Day 1) to 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.
- Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5 [Baseline (Day 1) to 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.
- Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1 [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.
- Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3 [Baseline (Day 1) to 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).
- Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3 [Baseline (Day 1) to 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.
- Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10 [Baseline (Day1) to 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.
- Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25 [Baseline (Day 1) to 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.
- Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3 [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.
- Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3 [Baseline (Day 1) to 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.
- Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3 [Baseline (Day 1) to 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.
- Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3 [Baseline (Day 1) to 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Arizona Eye Center | Chandler | Arizona | United States | 85224 |
2 | Schwartz Laser Eye Center | Scottsdale | Arizona | United States | 85260 |
3 | Assil Eye Institute | Beverly Hills | California | United States | 90210 |
4 | American Institute of Research | Los Angeles | California | United States | 90017 |
5 | Eye Research Foundation | Newport Beach | California | United States | 92663 |
6 | Martel Eye Medical Group | Rancho Cordova | California | United States | 95670 |
7 | Grutzmacher & Lewis, A Medical Corporation DBA Sacramento Eye Consultants | Sacramento | California | United States | 95815 |
8 | Haas Vision Center | Colorado Springs | Colorado | United States | 80919 |
9 | Danbury Eye Physicians and Surgeons P.C. | Danbury | Connecticut | United States | 06810 |
10 | The Eye Associates | Bradenton | Florida | United States | 34209 |
11 | Bruce Segal, MD | Delray Beach | Florida | United States | 33484 |
12 | Direct Helpers Research Center | Hialeah | Florida | United States | 33012 |
13 | Research Centers of America | Hollywood | Florida | United States | 33024 |
14 | Florida Eye Associates | Melbourne | Florida | United States | 32901 |
15 | USF Eye Institute | Tampa | Florida | United States | 33612 |
16 | Price Vision Group | Indianapolis | Indiana | United States | 46260 |
17 | Sabates Eye Centers | Leawood | Kansas | United States | 66211 |
18 | The Eye Care Institute | Louisville | Kentucky | United States | 40206 |
19 | Seidenberg Protzko Eye Associates | Havre De Grace | Maryland | United States | 21078 |
20 | Tauber Eye Center | Kansas City | Missouri | United States | 64111 |
21 | Alterman, Modi & Wolter | Poughkeepsie | New York | United States | 12603 |
22 | Rochester Ophthalmological Group, PC | Rochester | New York | United States | 14618 |
23 | Mundorf Eye Center | Charlotte | North Carolina | United States | 28204 |
24 | The Ohio State University | Columbus | Ohio | United States | 43212 |
25 | EyeCare Professionals DWA Insight Research Clinic, LLC | Powell | Ohio | United States | 43065 |
26 | Devers Eye Institute | Portland | Oregon | United States | 97210 |
27 | Scott & Christie and Associates, PC | Cranberry Township | Pennsylvania | United States | 16066 |
28 | Black Hills Regional Eye Institute | Rapid City | South Dakota | United States | 57701 |
29 | Vance Thompson Vision | Sioux Falls | South Dakota | United States | 57108 |
30 | Southern College of Optometry | Memphis | Tennessee | United States | 38104 |
31 | Nashville Vision Associates | Nashville | Tennessee | United States | 37205 |
32 | Hill Country Eye Center | Cedar Park | Texas | United States | 78613 |
33 | Key-Whitman Eye Center | Dallas | Texas | United States | 75243 |
34 | PNV Clinical Research LLC | San Antonio | Texas | United States | 78229 |
35 | R and R Eye Research, LLC | San Antonio | Texas | United States | 78229 |
36 | Hoopes, Durrie, Rivera Research | Draper | Utah | United States | 84020 |
Sponsors and Collaborators
- Allergan
Investigators
- Study Director: Eleonora Safyan, Allergan
Study Documents (Full-Text)
More Information
Publications
None provided.- 1883-301-013
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine hydrochloride (HCl) ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Period Title: Overall Study | ||
STARTED | 160 | 163 |
COMPLETED | 153 | 161 |
NOT COMPLETED | 7 | 2 |
Baseline Characteristics
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution | Total |
---|---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. | Total of all reporting groups |
Overall Participants | 160 | 163 | 323 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
49.7
(3.23)
|
49.5
(3.81)
|
49.6
(3.53)
|
Sex: Female, Male (Count of Participants) | |||
Female |
122
76.3%
|
113
69.3%
|
235
72.8%
|
Male |
38
23.8%
|
50
30.7%
|
88
27.2%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
26
16.3%
|
31
19%
|
57
17.6%
|
Not Hispanic or Latino |
134
83.8%
|
132
81%
|
266
82.4%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
2
1.3%
|
0
0%
|
2
0.6%
|
Asian |
1
0.6%
|
2
1.2%
|
3
0.9%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
12
7.5%
|
13
8%
|
25
7.7%
|
White |
144
90%
|
148
90.8%
|
292
90.4%
|
More than one race |
1
0.6%
|
0
0%
|
1
0.3%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) Population included all randomized participants. Missing data was imputed as non-responders. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 160 | 163 |
Number [percentage of participants] |
8.1
5.1%
|
30.7
18.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 22.5 | |
Confidence Interval |
(2-Sided) 95% 14.3 to 30.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction. |
Title | Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 6) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Missing data was imputed as non-responders. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 160 | 163 |
Number [percentage of participants] |
8.8
5.5%
|
18.4
11.3%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 9.7 | |
Confidence Interval |
(2-Sided) 95% 2.3 to 17.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction. |
Title | Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 8) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 153 | 161 |
Number [percentage of participants] |
8.5
5.3%
|
10.6
6.5%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 1.0000 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 2.1 | |
Confidence Interval |
(2-Sided) 95% -4.4 to 8.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction. |
Title | Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 0.5) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 153 | 158 |
Least Squares Mean (Standard Error) [letters read correctly] |
4.2
(0.55)
|
9.3
(0.54)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | MMRM with fixed effects: study intervention group,visit,visit by study intervention group interaction,age group,Baseline binocular DCNVA severity,iris color,emmetrope/non-emmetrope, Baseline value, and Baseline value by visit interaction was used. | |
Method | MMRM | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | Least Square (LS) Mean Difference |
Estimated Value | 5.1 | |
Confidence Interval |
(2-Sided) 95% 3.7 to 6.5 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
Estimation Comments |
Title | Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1 |
---|---|
Description | 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. |
Time Frame | Day 30 (Hour 1) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 153 | 161 |
Number [percentage of participants] |
73.9
46.2%
|
92.5
56.7%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 18.7 | |
Confidence Interval |
(2-Sided) 95% 10.6 to 26.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. 95% confidence interval was calculated based on normal approximation based on pooled variance without continuity correction. |
Title | Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3 |
---|---|
Description | 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). |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 148 | 154 |
Least Squares Mean (Standard Error) [score on a scale] |
0.6
(0.11)
|
1.4
(0.11)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | Analysis of covariance (ANCOVA) was used with study intervention group, age group, Baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and Baseline domain score as fixed effects. | |
Method | ANCOVA | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | 0.8 | |
Confidence Interval |
(2-Sided) 95% 0.6 to 1.1 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
Estimation Comments |
Title | Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 153 | 161 |
Least Squares Mean (Standard Error) [letters read correctly] |
3.1
(0.42)
|
6.6
(0.41)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | MMRM with fixed effects: study intervention group,visit,visit by study intervention group interaction,age group,Baseline binocular DCNVA severity,iris color,emmetrope/non-emmetrope, Baseline value, and Baseline value by visit interaction was used. | |
Method | MMRM | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | 3.5 | |
Confidence Interval |
(2-Sided) 95% 2.4 to 4.6 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.55 |
|
Estimation Comments |
Title | Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10 |
---|---|
Description | 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. |
Time Frame | Baseline (Day1) to Day 30 (Hour 10) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 152 | 160 |
Number [percentage of participants] |
8.6
5.4%
|
7.5
4.6%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 1.0000 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | -1.1 | |
Confidence Interval |
(2-Sided) 95% -7.1 to 5.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction. |
Title | Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 0.25) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 153 | 158 |
Least Squares Mean (Standard Error) [letters correctly read] |
3.7
(0.50)
|
6.3
(0.49)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | MMRM with fixed effects: study intervention group,visit,visit by study intervention group interaction,age group,Baseline binocular DCNVA severity,iris color,emmetrope/non-emmetrope, Baseline value, and Baseline value by visit interaction was used. | |
Method | MMRM | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | 2.6 | |
Confidence Interval |
(2-Sided) 95% 1.3 to 3.9 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
Estimation Comments |
Title | Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3 |
---|---|
Description | 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. |
Time Frame | Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 153 | 161 |
Number [percentage of participants] |
71.9
44.9%
|
84.5
51.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0171 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 12.6 | |
Confidence Interval |
(2-Sided) 95% 3.5 to 21.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction. |
Title | Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 148 | 154 |
Least Squares Mean (Standard Error) [score on a scale] |
0.6
(0.11)
|
1.4
(0.10)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | ANCOVA was used with study intervention group, age group, baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and baseline domain score as fixed effects. | |
Method | ANCOVA | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | 0.8 | |
Confidence Interval |
(2-Sided) 95% 0.5 to 1.1 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.13 |
|
Estimation Comments |
Title | Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 148 | 159 |
Least Squares Mean (Standard Error) [score on a scale] |
-0.5
(0.07)
|
-1.0
(0.07)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | ANCOVA was used with study intervention group, age group, Baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and Baseline domain score as fixed effects. | |
Method | ANCOVA | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | -0.5 | |
Confidence Interval |
(2-Sided) 95% -0.6 to -0.3 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
Estimation Comments |
Title | Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. |
Measure Participants | 148 | 159 |
Least Squares Mean (Standard Error) [score on a scale] |
-0.4
(0.06)
|
-0.7
(0.06)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Pilocarpine HCl Ophthalmic Solution |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0114 |
Comments | ANCOVA was used with study intervention group, age group, Baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and Baseline domain score as fixed effects. | |
Method | ANCOVA | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | -0.3 | |
Confidence Interval |
(2-Sided) 95% -0.4 to -0.1 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
Estimation Comments |
Adverse Events
Time Frame | First dose of study drug intervention to within 30 days after last dose (Up to 60 days) | |||
---|---|---|---|---|
Adverse Event Reporting Description | 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. | |||
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution | ||
Arm/Group Description | Participants received one drop of vehicle in each eye, once daily, for up to 30 days. | Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days. | ||
All Cause Mortality |
||||
Vehicle | Pilocarpine HCl Ophthalmic Solution | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/160 (0%) | 0/163 (0%) | ||
Serious Adverse Events |
||||
Vehicle | Pilocarpine HCl Ophthalmic Solution | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/159 (0%) | 0/163 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Vehicle | Pilocarpine HCl Ophthalmic Solution | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 15/159 (9.4%) | 23/163 (14.1%) | ||
Nervous system disorders | ||||
Headache | 15/159 (9.4%) | 23/163 (14.1%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Therapeutic Area, Head |
---|---|
Organization | Allergan |
Phone | 714-246-4500 |
clinicaltrials@allergan.com |
- 1883-301-013