Cataract
Conditions
Keywords
cataract, inflammation, pain, inflammatory cells, aqueous flare
Brief summary
The purpose of this study was to assess the safety and efficacy of Nepafenac Ophthalmic Suspension, 0.3% for the prevention and treatment of inflammation (swelling and redness) and pain in the eye after cataract extraction.
Interventions
Nepafenac Ophthalmic Suspension, 0.3%, one drop in affected eye once daily, for 16 days. An additional drop was administered between 30-120 minutes prior to surgery.
Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye once daily, for 16 days. An additional drop was administered between 30-120 minutes prior to surgery.
OTHERNepafenac Vehicle 0.3%
Nepafenac Vehicle 0.3%, one drop in affected eye once daily, for 16 days. An additional drop was administered between 30-120 minutes prior to surgery.
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Planned cataract extraction by phacoemulsification with the implantation of a posterior chamber intraocular lens; * Patients who, in the opinion of the Investigator, would have improvement in best-corrected visual acuity after surgery; * Able to understand and sign an informed consent; * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Use of topical ocular, inhaled or systemic nonsteroidal anti-inflammatory drugs within 7 days of surgery, with the exception of the allowed low dose of aspirin (up to 100 mg) prior to surgery and through study exit; * Use of topical ocular, inhaled or systemic steroids within 14 days prior to surgery and through study exit; * History of chronic or recurrent inflammatory eye disease (eg, iritis, scleritis, uveitis, iridocyclitis, rubeosis iridis) in the operative eye; * Diabetic retinopathy in the operative eye; * Known or suspected allergy or hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), or to any component of the test article; * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Cured at Day 14, Nepafenac 0.3% vs. Nepafenac Vehicle 0.3% | Day 14 postoperative | Ocular inflammation was assessed by the investigator during slit lamp examination. Aqueous cells were scored on a 5-unit scale from 0 (none) to 4 (\> 30 cells), and aqueous flare (protein escaping from dilated vessels) was scored on a 4-unit scale from 0 (no visible flare when compared with the normal eye) to 3 (severe - very dense flare). To be considered cured, the patient must have had a score of 0 for both aqueous cells and aqueous flare. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Cured at Day 7, Nepafenac 0.3% vs. Nepafenac 0.1% | Day 7 postoperative | Ocular inflammation was assessed by the investigator during slit lamp examination. Aqueous cells were scored on a 5-unit scale from 0 (none) to 4 (\> 30 cells), and aqueous flare (protein escaping from dilated vessels) was scored on a 4-unit scale from 0 (no visible flare when compared with the normal eye) to 3 (severe - very dense flare). To be considered cured, the patient must have had a score of 0 for both aqueous cells and aqueous flare. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Percentage of Patients Cured by Visit | Day 1, Day 3, Day 7, Day 14 | Ocular inflammation was assessed by the investigator during slit lamp examination. Aqueous cells were scored on a 5-unit scale from 0 (none) to 4 (\> 30 cells), and aqueous flare (protein escaping from dilated vessels) was scored on a 4-unit scale from 0 (no visible flare when compared with the normal eye) to 3 (severe - very dense flare). To be considered cured, the patient must have had a score of 0 for both aqueous cells and aqueous flare. To be included in the cumulative summary at a visit, a patient must have been declared cured at the visit and remained cured at all subsequent visits. |
| Cumulative Percentage of Patients Pain Free by Visit | Day 1, Day 3, Day 7, Day 14 | Ocular pain was assessed by the patient on a 6-unit scale from 0 (none; absence of positive sensation), to 5 (severe; intense ocular, periocular or radiating pain requiring prescription analgesic). Pain free was defined as an ocular pain assessment score of 0. To be included in the cumulative summary at a visit, a patient must have been declared pain free at the visit and remained pain free at all subsequent visits. |
Countries
United States
Participant flow
Recruitment details
Patients were randomized from 37 investigational sites in the US.
Pre-assignment details
Of the 1342 enrolled patients, 60 withdrew before the start of dosing. Baseline characteristics are presented on all randomized patients with at least one postoperative assessment (intent-to-treat): 1257
Participants by arm
| Arm | Count |
|---|---|
| Nepafenac 0.3% Nepafenac Ophthalmic Suspension, 0.3%, one drop in affected eye once daily, for 16 days, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery. An additional drop was administered between 30-120 minutes prior to surgery. | 512 |
| Nepafenac 0.1% Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye once daily, for 16 days, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery. An additional drop was administered between 30-120 minutes prior to surgery. | 493 |
| Nepafenac Vehicle 0.3% Nepafenac Vehicle 0.3%, one drop in affected eye once daily, for 16 days, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery. An additional drop was administered between 30-120 minutes prior to surgery. | 252 |
| Total | 1,257 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 11 | 6 |
| Overall Study | Noncompliance | 2 | 3 | 0 |
| Overall Study | Other | 7 | 10 | 22 |
| Overall Study | Patient Did Not Use Study Medication | 18 | 28 | 14 |
| Overall Study | Protocol Violation | 2 | 4 | 2 |
| Overall Study | Pt Decision Unrelated to Adverse Event | 1 | 1 | 2 |
| Overall Study | Treatment Failure | 19 | 19 | 101 |
Baseline characteristics
| Characteristic | Nepafenac 0.3% | Nepafenac 0.1% | Nepafenac Vehicle 0.3% | Total |
|---|---|---|---|---|
| Age Continuous | 69.3 years STANDARD_DEVIATION 9.26 | 69.4 years STANDARD_DEVIATION 9.15 | 69.3 years STANDARD_DEVIATION 9.6 | 69.3 years STANDARD_DEVIATION 9.28 |
| Region of Enrollment United States | 512 participants | 493 participants | 252 participants | 1257 participants |
| Sex: Female, Male Female | 282 Participants | 301 Participants | 142 Participants | 725 Participants |
| Sex: Female, Male Male | 230 Participants | 192 Participants | 110 Participants | 532 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 522 | 0 / 506 | 0 / 254 |
| serious Total, serious adverse events | 5 / 522 | 4 / 506 | 0 / 254 |
Outcome results
Primary
Percentage of Patients Cured at Day 14, Nepafenac 0.3% vs. Nepafenac Vehicle 0.3%
Ocular inflammation was assessed by the investigator during slit lamp examination. Aqueous cells were scored on a 5-unit scale from 0 (none) to 4 (\> 30 cells), and aqueous flare (protein escaping from dilated vessels) was scored on a 4-unit scale from 0 (no visible flare when compared with the normal eye) to 3 (severe - very dense flare). To be considered cured, the patient must have had a score of 0 for both aqueous cells and aqueous flare.
Time frame: Day 14 postoperative
Population: All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac 0.3% | Percentage of Patients Cured at Day 14, Nepafenac 0.3% vs. Nepafenac Vehicle 0.3% | 64.6 Percentage of patients |
| Nepafenac Vehicle 0.3% | Percentage of Patients Cured at Day 14, Nepafenac 0.3% vs. Nepafenac Vehicle 0.3% | 25.0 Percentage of patients |
Secondary
Percentage of Patients Cured at Day 7, Nepafenac 0.3% vs. Nepafenac 0.1%
Ocular inflammation was assessed by the investigator during slit lamp examination. Aqueous cells were scored on a 5-unit scale from 0 (none) to 4 (\> 30 cells), and aqueous flare (protein escaping from dilated vessels) was scored on a 4-unit scale from 0 (no visible flare when compared with the normal eye) to 3 (severe - very dense flare). To be considered cured, the patient must have had a score of 0 for both aqueous cells and aqueous flare.
Time frame: Day 7 postoperative
Population: All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepafenac 0.3% | Percentage of Patients Cured at Day 7, Nepafenac 0.3% vs. Nepafenac 0.1% | 31.3 Percentage of patients |
| Nepafenac Vehicle 0.3% | Percentage of Patients Cured at Day 7, Nepafenac 0.3% vs. Nepafenac 0.1% | 30.8 Percentage of patients |
Other Pre-specified
Cumulative Percentage of Patients Cured by Visit
Ocular inflammation was assessed by the investigator during slit lamp examination. Aqueous cells were scored on a 5-unit scale from 0 (none) to 4 (\> 30 cells), and aqueous flare (protein escaping from dilated vessels) was scored on a 4-unit scale from 0 (no visible flare when compared with the normal eye) to 3 (severe - very dense flare). To be considered cured, the patient must have had a score of 0 for both aqueous cells and aqueous flare. To be included in the cumulative summary at a visit, a patient must have been declared cured at the visit and remained cured at all subsequent visits.
Time frame: Day 1, Day 3, Day 7, Day 14
Population: All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nepafenac 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 1 | 0.4 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 3 | 6.4 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 7 | 31.3 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 14 | 64.6 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 14 | 65.3 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 1 | 1.8 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 7 | 30.8 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 3 | 7.1 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 14 | 25.0 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 3 | 3.2 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 7 | 10.3 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Cured by Visit | Day 1 | 0.4 Percentage of patients |
Other Pre-specified
Cumulative Percentage of Patients Pain Free by Visit
Ocular pain was assessed by the patient on a 6-unit scale from 0 (none; absence of positive sensation), to 5 (severe; intense ocular, periocular or radiating pain requiring prescription analgesic). Pain free was defined as an ocular pain assessment score of 0. To be included in the cumulative summary at a visit, a patient must have been declared pain free at the visit and remained pain free at all subsequent visits.
Time frame: Day 1, Day 3, Day 7, Day 14
Population: All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nepafenac 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 1 | 65.2 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 3 | 77.3 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 7 | 84.8 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 14 | 89.1 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 14 | 89.0 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 1 | 61.9 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 7 | 83.0 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 3 | 75.9 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 14 | 40.1 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 3 | 25.8 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 7 | 31.7 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percentage of Patients Pain Free by Visit | Day 1 | 17.5 Percentage of patients |
Post Hoc
Cumulative Percent Clinical Success by Visit
Ocular inflammation was assessed by the investigator during slit lamp examination. Aqueous cells were scored on a 5-unit scale from 0 (none) to 4 (\> 30 cells), and aqueous flare (protein escaping from dilated vessels) was scored on a 4-unit scale from 0 (no visible flare when compared with the normal eye) to 3 (severe - very dense flare). Clinical success occurred when the cell grade was ≤ 1 (0-5 cells) and flare grade was = 0. To be included in the cumulative summary at a visit, a patient must have been declared a clinical success at the visit and remained a clinical success at all subsequent visits.
Time frame: Day 1, Day 3, Day 7, Day 14
Population: All randomized patients with at least one post-operative assessment (intent-to-treat).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nepafenac 0.3% | Cumulative Percent Clinical Success by Visit | Day 1 | 18.9 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percent Clinical Success by Visit | Day 3 | 43.9 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percent Clinical Success by Visit | Day 7 | 71.9 Percentage of patients |
| Nepafenac 0.3% | Cumulative Percent Clinical Success by Visit | Day 14 | 84.8 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 14 | 81.3 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 1 | 15.0 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 7 | 62.5 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 3 | 35.9 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 14 | 37.7 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 3 | 18.7 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 7 | 29.4 Percentage of patients |
| Nepafenac Vehicle 0.3% | Cumulative Percent Clinical Success by Visit | Day 1 | 12.3 Percentage of patients |