Cataract, Non-Proliferative Diabetic Retinopathy
Conditions
Keywords
Diabetes Type I, Diabetes Type II, non-proliferative diabetic retinopathy, macular edema, Cataract
Brief summary
The purpose of this study is to demonstrate superiority of Nepafenac Ophthalmic Suspension, 0.3% dosed once daily relative to Nepafenac Vehicle based upon clinical outcomes among diabetic subjects following cataract surgery.
Interventions
Test intervention
OTHERNepafenac vehicle
Inactive ingredients used as placebo comparator
DRUGPrednisolone acetate
1 drop instilled in the operative eye 4 times daily beginning post-operatively on the day of surgery for the first 2 weeks, followed by 2 times daily for the next 2 weeks
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Planned cataract extraction by phacoemulsification with implantation of a posterior chamber intraocular lens; * History of Type 1 or 2 diabetes and non-proliferative diabetic retinopathy (NPDR) (mild, moderate, or severe) in the study eye; * Best corrected visual acuity (BCVA) of 73 letters or worse in the study eye with expectation of improvement after surgery; * Understand and sign an informed consent document; * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Pre-existing macular edema in the study eye; * History in the study eye of retinal detachment, wet age-related macular degeneration, chronic or recurrent inflammatory eye disease, or prior procedures; * Planned cataract surgery in the fellow eye after randomization and prior to the Day 90 postoperative study visit or through study exit; * Planned multiple procedures for the study eye during the cataract/intraocular lens implantation surgery; * Use of exclusionary medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids, as specified in protocol. * Participation in any other clinical study within 30 days of the screening visit; * Females of childbearing potential who are breast feeding, have a positive urine pregnancy test at screening, are not willing to undergo a urine pregnancy test upon entering or exiting the study, intend to become pregnant during the study, or do not agree to use adequate birth control methods for the duration of the study; * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best-corrected Visual Acuity (BCVA) Improvement of ≥ 15 Letters From Preoperative Baseline to Day 14 and Maintained Through Day 90 | Baseline to Day 14, and maintained through Day 90 | BCVA (with spectacles or other visual corrective devices) was reported in letters read correctly, using the Early Treatment Diabetic Retinopathy Study (ETDRS) test of 70 letters. Improvement of BCVA was defined as an increase (gain) in the number of letters read, compared to the baseline assessment. One eye (study eye) contributed to the analysis. |
| Percentage of Participants Who Develop Macular Edema Within 90 Days Following Cataract Surgery (Day 0) | Day 0 to Day 90 | Macular edema was defined as ≥ 30% Increase from pre-operative baseline in central subfield macular thickness, as measured with Spectral Domain Ocular Coherence Tomography (SD-OCT). One eye (study eye) contributed to the analysis. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 90 | Baseline to Day 90 |
| Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 60 | Baseline to Day 60 |
| Percentage of Participants With a > 5-letter Loss in BCVA From Day 7 to Any Visit [Time Frame: Day 7 up to Any Visit] | Day 7 up to any visit through Day 90 |
| Percentage of Participants With With a > 10-letter Loss in BCVA From Day 7 to Any Visit | Day 7 up to any visit through Day 90 |
Participant flow
Recruitment details
Participants were recruited from 66 investigational centers located in the U.S., Latin America, and the Caribbean.
Pre-assignment details
Of the 881 participants enrolled, 253 were exited as screen failures and 13 were discontinued prior to randomization. This reporting group includes all randomized participants (615).
Participants by arm
| Arm | Count |
|---|---|
| Nepafenac Nepafenac Ophthalmic Suspension, 0.3% | 298 |
| Vehicle Nepafenac Ophthalmic Suspension Vehicle | 300 |
| Total | 598 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Adverse event prior to treatment | 0 | 1 |
| Overall Study | Death | 1 | 4 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Non-compliance with study drug | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Reason not specified | 9 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Nepafenac | Vehicle | Total |
|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 8.5 | 66.8 years STANDARD_DEVIATION 8.3 | 66.8 years STANDARD_DEVIATION 8.4 |
| Sex: Female, Male Female | 158 Participants | 166 Participants | 324 Participants |
| Sex: Female, Male Male | 140 Participants | 134 Participants | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 881 | 0 / 301 | 0 / 302 | 0 / 603 |
| serious Total, serious adverse events | 14 / 881 | 13 / 301 | 14 / 302 | 9 / 603 |
Outcome results
Primary
Percentage of Participants Who Develop Macular Edema Within 90 Days Following Cataract Surgery (Day 0)
Macular edema was defined as ≥ 30% Increase from pre-operative baseline in central subfield macular thickness, as measured with Spectral Domain Ocular Coherence Tomography (SD-OCT). One eye (study eye) contributed to the analysis.
Time frame: Day 0 to Day 90
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac | Percentage of Participants Who Develop Macular Edema Within 90 Days Following Cataract Surgery (Day 0) | 2.3 Percentage of participants |
| Vehicle | Percentage of Participants Who Develop Macular Edema Within 90 Days Following Cataract Surgery (Day 0) | 17.3 Percentage of participants |
Comparison: This endpoint was considered primary for EU registration and secondary for US registration.p-value: <0.00195% CI: [0.1, 0.3]Regression, Logistic
Primary
Percentage of Participants With Best-corrected Visual Acuity (BCVA) Improvement of ≥ 15 Letters From Preoperative Baseline to Day 14 and Maintained Through Day 90
BCVA (with spectacles or other visual corrective devices) was reported in letters read correctly, using the Early Treatment Diabetic Retinopathy Study (ETDRS) test of 70 letters. Improvement of BCVA was defined as an increase (gain) in the number of letters read, compared to the baseline assessment. One eye (study eye) contributed to the analysis.
Time frame: Baseline to Day 14, and maintained through Day 90
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac | Percentage of Participants With Best-corrected Visual Acuity (BCVA) Improvement of ≥ 15 Letters From Preoperative Baseline to Day 14 and Maintained Through Day 90 | 61.7 Percentage of participants |
| Vehicle | Percentage of Participants With Best-corrected Visual Acuity (BCVA) Improvement of ≥ 15 Letters From Preoperative Baseline to Day 14 and Maintained Through Day 90 | 43.0 Percentage of participants |
Comparison: This endpoint was considered primary for United States (US) registration and secondary for European Union (EU) registration.p-value: <0.00195% CI: [1.5, 3]Regression, Logistic
Secondary
Percentage of Participants With a > 5-letter Loss in BCVA From Day 7 to Any Visit [Time Frame: Day 7 up to Any Visit]
Time frame: Day 7 up to any visit through Day 90
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac | Percentage of Participants With a > 5-letter Loss in BCVA From Day 7 to Any Visit [Time Frame: Day 7 up to Any Visit] | 15.4 percentage of participants |
| Vehicle | Percentage of Participants With a > 5-letter Loss in BCVA From Day 7 to Any Visit [Time Frame: Day 7 up to Any Visit] | 27.3 percentage of participants |
Secondary
Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 60
Time frame: Baseline to Day 60
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac | Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 60 | 76.2 Percentage of participants |
| Vehicle | Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 60 | 64.7 Percentage of participants |
Secondary
Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 90
Time frame: Baseline to Day 90
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac | Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 90 | 77.2 Percentage of participants |
| Vehicle | Percentage of Participants With BCVA Improvement of ≥ 15 Letters From Preoperative Baseline to Day 90 | 67.7 Percentage of participants |
Secondary
Percentage of Participants With With a > 10-letter Loss in BCVA From Day 7 to Any Visit
Time frame: Day 7 up to any visit through Day 90
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac | Percentage of Participants With With a > 10-letter Loss in BCVA From Day 7 to Any Visit | 9.1 percentage of participants |
| Vehicle | Percentage of Participants With With a > 10-letter Loss in BCVA From Day 7 to Any Visit | 15.3 percentage of participants |