GEMINI 2: A Phase 3 Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia
Study Details
Study Description
Brief Summary
This clinical study will evaluate pilocarpine hydrogen chloride (HCl) ophthalmic solution (AGN-190584) in an expanded participant population to establish efficacy, safety, and tolerability versus the vehicle-control when administered, over a 30-day study intervention period, once daily bilaterally in participants with presbyopia.
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 DCNVA, Without Losing More Than 5 Letters of Mesopic, High-Contrast, Binocular CDVA With the Same Refractive Correction at Day 30, Hour 3 [Baseline (Day 1) to Day 30 (Hour 3)]
Visual acuity for near (40 centimeter (cm)) and distance (4 meter (m)) targets were measured in mesopic conditions using an eye chart. High contrast corrected distance visual acuity (CDVA) was assessed binocularly (in each eye) using the provided visual acuity charts for distance vision in a room with mesopic lighting conditions measured at the target. Forced choice letter by-letter scoring was used for each test and the total number of correct letters or the highest value (number) of the grid identified (as applicable) were recorded. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. DCNVA= distance-corrected near visual acuity.
Secondary Outcome Measures
- Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular 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 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.
- 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) 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.
- 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 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.
- 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.
- 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 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).
- 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. MMRM was used for the analysis.
- Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10 [Baseline (Day 1) to Day 30 (Hour 10)]
Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported.
- 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 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.
- 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) 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.
- 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 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.
- Mean Change From Baseline in Presbyopia 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. 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.
Eligibility Criteria
Criteria
Inclusion Criteria
Subjective complaints of poor near vision that impact activities of daily living
Exclusion Criteria
Uncontrolled systemic disease
Any clinical condition or previous surgery that might affect the absorption, distribution, biotransformation, or excretion of AGN-190584. History of cataract surgery, phakic intraocular lens surgery, corneal inlay surgery, radial keratotomy, or any intraocular surgery. However, participants with history of photorefractive keratectomy (PRK) or laser-assisted in situ keratomileusis (LASIK) with corrected distance visual acuity (CDVA) meeting inclusion criteria will be allowed to enroll.
Known allergy or sensitivity to the study intervention or its components or other cholinergic agonist medications
Concurrent use of any topical ophthalmic medications, including artificial tears, other than the study intervention during the course of the study
Concurrent use of temporary or permanent punctal plugs or history of punctal cautery in one or both eyes
Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study
Participation in a blood or plasma donation program within 30 days prior to study intervention administration
Severe dry eye disease (defined as total corneal staining ≥ grade 3 on the 5-point Oxford scale and an ocular surface disease index (OSDI) score of > 33) at the screening visit
Corneal abnormalities (including keratoconus, corneal scar, Fuchs' endothelial dystrophy, guttata, or edema) in either eye that are likely to interfere with visual acuity
Narrow iridocorneal angles (Shaffer grade ≤ 2 or lower on gonioscopy examination), history of angle-closure glaucoma, or previous iridotomy
History of iris trauma, Adie's tonic pupil, abnormal pupil shape in either eye, or anisocoria > 1 mm between pupils under mesopic conditions at the screening visit
Lens opacity in either eye that is determined to cause significant disturbance of the central visual axis on screening biomicroscopy
Diagnosis of any type of glaucoma or ocular hypertension
Bifocal or multifocal spectacles or contact lenses for habitual correction. Participants willing to wear study-provided monofocal correction (either spectacles or contact lenses) during the study can be enrolled
Abnormal and clinically significant results according to the investigator or designee, on physical/ophthalmic examination or medical history
Females who are pregnant, nursing, or planning a pregnancy during the study
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Eye Center South | Dothan | Alabama | United States | 36301 |
2 | M&M Eye Institute | Prescott | Arizona | United States | 86301 |
3 | Walman Eye Center | Sun City | Arizona | United States | 85351 |
4 | Milton M. Hom, OD, FAAO | Azusa | California | United States | 91702 |
5 | Global Research Management | Glendale | California | United States | 91204 |
6 | Advanced Vision Care | Los Angeles | California | United States | 90067 |
7 | North Valley Eye Medical Group, Inc. | Mission Hills | California | United States | 91345 |
8 | Eye Research Foundation | Newport Beach | California | United States | 92663 |
9 | Corneal Consultants of Colorado | Littleton | Colorado | United States | 80120 |
10 | Benjamin Knox Lambright, MD | Crystal River | Florida | United States | 34429 |
11 | South Florida Vision Center | Fort Lauderdale | Florida | United States | 33309 |
12 | Bowden Eye Associates | Jacksonville | Florida | United States | 32256 |
13 | Mid Florida Eye Center | Mount Dora | Florida | United States | 32757 |
14 | Newsom Eye & Laser Center | Sebring | Florida | United States | 33870 |
15 | Clayton Eye Center | Morrow | Georgia | United States | 30260 |
16 | The Midwest Center for Sight | Des Plaines | Illinois | United States | 60016 |
17 | Jacksoneye | Lake Villa | Illinois | United States | 60046 |
18 | Kannarr Eye Care | Pittsburg | Kansas | United States | 66762 |
19 | Heart of America Eyecare | Shawnee Mission | Kansas | United States | 66204 |
20 | Cincinnati Eye Institute | Edgewood | Kentucky | United States | 41017 |
21 | Chu Laser Eye Institute | Bloomington | Minnesota | United States | 55420 |
22 | Silverstein Eye Centers | Kansas City | Missouri | United States | 64133 |
23 | Moyes Eye Center | Kansas City | Missouri | United States | 64154 |
24 | Tekwani Vision Center | Saint Louis | Missouri | United States | 63128 |
25 | Amel Youssef, OD | Las Vegas | Nevada | United States | 89117 |
26 | Debry Medical Services PC | Las Vegas | Nevada | United States | 89128 |
27 | Bucci Laser Vision | Wilkes-Barre | Pennsylvania | United States | 18702 |
28 | Waring Vision Institute | Mount Pleasant | South Carolina | United States | 29464 |
29 | University Eye Surgeons | Maryville | Tennessee | United States | 37803 |
30 | Total Eye Care, PA | Memphis | Tennessee | United States | 38119 |
31 | Keystone Research ltd. at Texan Eye | Austin | Texas | United States | 78731 |
32 | The Cataract and Glaucoma Center | El Paso | Texas | United States | 79902 |
33 | Texas Eye & Laser Ctr | Hurst | Texas | United States | 76054 |
34 | Benjamin Travis Dastrup, MD | Ogden | Utah | United States | 84403 |
35 | Vision Consultants and Surgeons | Falls Church | Virginia | United States | 22046 |
Sponsors and Collaborators
- Allergan
Investigators
- Study Director: Eleonora Safyan, Allergan
Study Documents (Full-Text)
More Information
Publications
None provided.- 1883-302-013
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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. |
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 | 215 | 212 |
COMPLETED | 209 | 207 |
NOT COMPLETED | 6 | 5 |
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 | 215 | 212 | 427 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
49.9
(3.48)
|
49.6
(3.71)
|
49.8
(3.60)
|
Sex: Female, Male (Count of Participants) | |||
Female |
162
75.3%
|
138
65.1%
|
300
70.3%
|
Male |
53
24.7%
|
74
34.9%
|
127
29.7%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
41
19.1%
|
37
17.5%
|
78
18.3%
|
Not Hispanic or Latino |
174
80.9%
|
175
82.5%
|
349
81.7%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
2
0.9%
|
1
0.5%
|
3
0.7%
|
Asian |
8
3.7%
|
5
2.4%
|
13
3%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
29
13.5%
|
35
16.5%
|
64
15%
|
White |
176
81.9%
|
171
80.7%
|
347
81.3%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
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 DCNVA, Without Losing More Than 5 Letters of Mesopic, High-Contrast, Binocular CDVA With the Same Refractive Correction at Day 30, Hour 3 |
---|---|
Description | 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Missing data was imputed as non-responders; excluding data from 1 site. |
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 | 203 | 196 |
Number [percentage of participants] |
10.8
5%
|
26.0
12.3%
|
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 | <.0001 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 15.2 | |
Confidence Interval |
(2-Sided) 95% 7.7 to 22.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. The 95% confidence intervals for the proportion differences were 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 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 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 6) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Missing data was imputed as non-responders; excluding data from 1 site. |
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 | 203 | 196 |
Number [percentage of participants] |
9.9
4.6%
|
16.3
7.7%
|
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 | 0.0548 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 6.5 | |
Confidence Interval |
(2-Sided) 95% -0.1 to 13.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. The 95% confidence intervals for the proportion difference 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) 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 8) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
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 | 197 | 193 |
Number [percentage of participants] |
8.6
4%
|
14.5
6.8%
|
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 | 0.0693 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 5.9 | |
Confidence Interval |
(2-Sided) 95% -0.5 to 12.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using Chi-square test. The 95% confidence intervals for the proportion difference 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 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. |
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 of participants analyzed is the number of participants with data available for analysis; excluding data from 1 site. |
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 | 197 | 193 |
Least Squares Mean (Standard Error) [letters read correctly] |
4.7
(0.44)
|
8.8
(0.44)
|
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 | <.0001 |
Comments | MMRM with study intervention group, visit, visit by study intervention group interaction, age group, Baseline binocular DCNVA severity, iris color, emmetrope/non-emmetrope, Baseline value; Baseline value by visit interaction as fixed effects. | |
Method | MMRM | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
Estimated Value | 4.1 | |
Confidence Interval |
(2-Sided) 95% 2.9 to 5.2 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.59 |
|
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. |
Time Frame | Day 30 (Hour 1) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
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 | 198 | 193 |
Number [percentage of participants] |
82.8
38.5%
|
92.7
43.7%
|
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 | 0.0141 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 9.9 | |
Confidence Interval |
(2-Sided) 95% 3.5 to 16.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using chi-square test. The 95% confidence intervals 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 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). |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
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 | 197 | 192 |
Least Squares Mean (Standard Error) [score on a scale] |
0.5
(0.09)
|
1.3
(0.09)
|
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 | <.0001 |
Comments | Analysis of covariance (ANCOVA) 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 1.0 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
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. MMRM was used for the analysis. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
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 | 198 | 193 |
Least Squares Mean (Standard Error) [number of letters read correctly] |
2.9
(0.38)
|
6.4
(0.39)
|
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 | <.0001 |
Comments | MMRM with 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 as fixed effects. | |
Method | MMRM | |
Comments | P-value was adjusted for multiplicity control. | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | 3.4 | |
Confidence Interval |
(2-Sided) 95% 2.4 to 4.4 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
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 (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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 10) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
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 | 195 | 191 |
Number [percentage of participants] |
8.7
4%
|
12.6
5.9%
|
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 | 0.2200 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 3.8 | |
Confidence Interval |
(2-Sided) 95% -2.3 to 10.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using chi-square test. The 95% confidence intervals for the proportion differences were 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 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. |
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 of participants analyzed is the number of participants with data available for analysis; excluding data from 1 site. |
Arm/Group Title | Vehicle | Pilocarpine HCl Ophthalmic Solution 1.25% |
---|---|---|
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 | 196 | 193 |
Least Squares Mean (Standard Error) [letters read correctly] |
3.9
(0.41)
|
6.5
(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 | <.0001 |
Comments | MMRM with 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 as fixed effects. | |
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% 1.5 to 3.7 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.55 |
|
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) 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. |
Time Frame | Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population included all randomized participants. Overall number of participants analyzed is the number of participants with data available 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 | 198 | 193 |
Number [percentage of participants] |
77.8
36.2%
|
90.2
42.5%
|
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 | 0.0141 |
Comments | P-value was adjusted for multiplicity control. | |
Method | Chi-squared | |
Comments | ||
Method of Estimation | Estimation Parameter | Percentage Difference |
Estimated Value | 12.4 | |
Confidence Interval |
(2-Sided) 95% 5.2 to 19.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Analysis was done using chi-square test. The 95% confidence intervals was calculated based on 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 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
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 | 197 | 192 |
Least Squares Mean (Standard Error) [score on a scale] |
0.5
(0.08)
|
1.2
(0.08)
|
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 | <.0001 |
Comments | ANCOVA 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 | 0.7 | |
Confidence Interval |
(2-Sided) 95% 0.5 to 1.0 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
Estimation Comments |
Title | Mean Change From Baseline in Presbyopia 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 of participants analyzed is the number of participants with data available for analysis. ANCOVA was used for the 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 | 197 | 193 |
Least Squares Mean (Standard Error) [score on a scale] |
-0.5
(0.06)
|
-0.9
(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 | 0.0002 |
Comments | ANCOVA 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 | -0.4 | |
Confidence Interval |
(2-Sided) 95% -0.5 to -0.2 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
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. 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. |
Time Frame | Baseline (Day 1) to Day 30 (Hour 3) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
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 | 197 | 193 |
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 | 0.0002 |
Comments | ANCOVA 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 -0.2 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.07 |
|
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 | ||||
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 | 0/215 (0%) | 0/212 (0%) | ||
Serious Adverse Events |
||||
Vehicle | Pilocarpine HCl Ophthalmic Solution | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/215 (0.9%) | 0/212 (0%) | ||
Gastrointestinal disorders | ||||
Dysphagia | 1/215 (0.5%) | 0/212 (0%) | ||
Nervous system disorders | ||||
Guillain-Barre syndrome | 1/215 (0.5%) | 0/212 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Vehicle | Pilocarpine HCl Ophthalmic Solution | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 25/215 (11.6%) | 58/212 (27.4%) | ||
Eye disorders | ||||
Conjunctival hyperaemia | 11/215 (5.1%) | 15/212 (7.1%) | ||
Vision blurred | 1/215 (0.5%) | 13/212 (6.1%) | ||
Eye pain | 3/215 (1.4%) | 12/212 (5.7%) | ||
Nervous system disorders | ||||
Headache | 11/215 (5.1%) | 33/212 (15.6%) |
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 |
- 1883-302-013