Nepafenac 0.3% Two Study

Sponsor
Alcon Research (Industry)
Overall Status
Completed
CT.gov ID
NCT01318499
Collaborator
(none)
1,342
Enrollment
1
Location
3
Arms
6
Duration (Months)
222
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Nepafenac Ophthalmic Suspension, 0.3%
  • Drug: Nepafenac Ophthalmic Suspension, 0.1%
  • Other: Nepafenac Vehicle 0.3%
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
1342 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Clinical Evaluation of Nepafenac Ophthalmic Suspension, 0.3% Compared to Nepafenac Ophthalmic Suspension 0.1% and Vehicle for Prevention and Treatment of Ocular Inflammation and Pain Associated With Cataract Surgery
Study Start Date :
Mar 1, 2011
Actual Primary Completion Date :
Sep 1, 2011
Actual Study Completion Date :
Sep 1, 2011

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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.

Drug: Nepafenac Ophthalmic Suspension, 0.3%
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.

Active Comparator: 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.

Drug: Nepafenac Ophthalmic Suspension, 0.1%
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.
Other Names:
  • NEVANAC®
  • Placebo Comparator: 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.

    Other: Nepafenac 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.

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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 Outcome Measures

    1. 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.

    2. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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 exclusion criteria may apply.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Contact Alcon Call Center for Trial LocationsFort WorthTexasUnited States76134

    Sponsors and Collaborators

    • Alcon Research

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alcon Research
    ClinicalTrials.gov Identifier:
    NCT01318499
    Other Study ID Numbers:
    • C-11-003
    First Posted:
    Mar 18, 2011
    Last Update Posted:
    Dec 17, 2012
    Last Verified:
    Dec 1, 2012
    Keywords provided by Alcon Research
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsPatients were randomized from 37 investigational sites in the US.
    Pre-assignment DetailOf 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
    Arm/Group TitleNepafenac 0.3%Nepafenac 0.1%Nepafenac Vehicle 0.3%
    Arm/Group DescriptionNepafenac 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.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.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.
    Period Title: Overall Study
    STARTED540534268
    COMPLETED475458121
    NOT COMPLETED6576147

    Baseline Characteristics

    Arm/Group TitleNepafenac 0.3%Nepafenac 0.1%Nepafenac Vehicle 0.3%Total
    Arm/Group DescriptionNepafenac 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.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.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.Total of all reporting groups
    Overall Participants5124932521257
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    69.3
    (9.26)
    69.4
    (9.15)
    69.3
    (9.6)
    69.3
    (9.28)
    Sex: Female, Male (Count of Participants)
    Female
    282
    55.1%
    301
    61.1%
    142
    56.3%
    725
    57.7%
    Male
    230
    44.9%
    192
    38.9%
    110
    43.7%
    532
    42.3%
    Region of Enrollment (participants) [Number]
    United States
    512
    100%
    493
    100%
    252
    100%
    1257
    100%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Patients Cured at Day 14, Nepafenac 0.3% vs. Nepafenac Vehicle 0.3%
    DescriptionOcular 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 FrameDay 14 postoperative

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
    Arm/Group TitleNepafenac 0.3%Nepafenac Vehicle 0.3%
    Arm/Group DescriptionNepafenac 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.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.
    Measure Participants512252
    Number [Percentage of patients]
    64.6
    25.0
    2. Secondary Outcome
    TitlePercentage of Patients Cured at Day 7, Nepafenac 0.3% vs. Nepafenac 0.1%
    DescriptionOcular 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 FrameDay 7 postoperative

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
    Arm/Group TitleNepafenac 0.3%Nepafenac 0.1%
    Arm/Group DescriptionNepafenac 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.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.
    Measure Participants512493
    Number [Percentage of patients]
    31.3
    30.8
    3. Post-Hoc Outcome
    TitleCumulative Percent Clinical Success by Visit
    DescriptionOcular 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 FrameDay 1, Day 3, Day 7, Day 14

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with at least one post-operative assessment (intent-to-treat).
    Arm/Group TitleNepafenac 0.3%Nepafenac 0.1%Nepafenac Vehicle 0.3%
    Arm/Group DescriptionNepafenac 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.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.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.
    Measure Participants512493252
    Day 1
    18.9
    15.0
    12.3
    Day 3
    43.9
    35.9
    18.7
    Day 7
    71.9
    62.5
    29.4
    Day 14
    84.8
    81.3
    37.7
    4. Other Pre-specified Outcome
    TitleCumulative Percentage of Patients Cured by Visit
    DescriptionOcular 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 FrameDay 1, Day 3, Day 7, Day 14

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
    Arm/Group TitleNepafenac 0.3%Nepafenac 0.1%Nepafenac 0.3% Vehicle
    Arm/Group DescriptionNepafenac 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.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.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.
    Measure Participants512493252
    Day 1
    0.4
    1.8
    0.4
    Day 3
    6.4
    7.1
    3.2
    Day 7
    31.3
    30.8
    10.3
    Day 14
    64.6
    65.3
    25.0
    5. Other Pre-specified Outcome
    TitleCumulative Percentage of Patients Pain Free by Visit
    DescriptionOcular 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 FrameDay 1, Day 3, Day 7, Day 14

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.
    Arm/Group TitleNepafenac 0.3%Nepafenac 0.1%Nepafenac 0.3% Vehicle
    Arm/Group DescriptionNepafenac 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.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.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.
    Measure Participants512493252
    Day 1
    65.2
    61.9
    17.5
    Day 3
    77.3
    75.9
    25.8
    Day 7
    84.8
    83.0
    31.7
    Day 14
    89.1
    89.0
    40.1

    Adverse Events

    Time FrameAdverse events were collected for the duration of the study.
    Adverse Event Reporting Description The safety population includes all patients who received study medication, or potentially received study medication: 1282. At each study visit, the patient received an ocular exam, and any changes in ocular and systemic medications and/or systemic diseases/conditions since surgery were recorded.
    Arm/Group TitleNepafenac 0.3%Nepafenac 0.1%Nepafenac Vehicle 0.3%
    Arm/Group DescriptionNepafenac 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.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.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.
    All Cause Mortality
    Nepafenac 0.3%Nepafenac 0.1%Nepafenac Vehicle 0.3%
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Nepafenac 0.3%Nepafenac 0.1%Nepafenac Vehicle 0.3%
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/522 (1%) 4/506 (0.8%) 0/254 (0%)
    Cardiac disorders
    Cardiac failure congestive1/522 (0.2%) 0/506 (0%) 0/254 (0%)
    Eye disorders
    Angle closure glaucoma1/522 (0.2%) 0/506 (0%) 0/254 (0%)
    Lens dislocation1/522 (0.2%) 0/506 (0%) 0/254 (0%)
    Retinal detachment1/522 (0.2%) 0/506 (0%) 0/254 (0%)
    Visual acuity reduced0/522 (0%) 1/506 (0.2%) 0/254 (0%)
    Infections and infestations
    Endophthalmitis1/522 (0.2%) 0/506 (0%) 0/254 (0%)
    Hypopyon1/522 (0.2%) 0/506 (0%) 0/254 (0%)
    Gastritis viral0/522 (0%) 1/506 (0.2%) 0/254 (0%)
    Injury, poisoning and procedural complications
    Corneal abrasion1/522 (0.2%) 0/506 (0%) 0/254 (0%)
    Injury0/522 (0%) 1/506 (0.2%) 0/254 (0%)
    Nervous system disorders
    Hypertensive encephalopathy0/522 (0%) 1/506 (0.2%) 0/254 (0%)
    Other (Not Including Serious) Adverse Events
    Nepafenac 0.3%Nepafenac 0.1%Nepafenac Vehicle 0.3%
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/522 (0%) 0/506 (0%) 0/254 (0%)

    Limitations/Caveats

    Study excluded patients who were under the age of 18, had uncontrolled glaucoma, were at risk of developing macular edema (diabetic retinopathy), and women of childbearing potential. Therefore, results may not be generalizable to these populations.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor reserves the right of prior review of any publication or presentation of information related to the study.

    Results Point of Contact

    Name/TitleDana Sager, Clinical Manager Group Leader
    OrganizationAlcon Research
    Phone1-817-551-8603
    Emaildana.sager@alconlabs.com
    Responsible Party:
    Alcon Research
    ClinicalTrials.gov Identifier:
    NCT01318499
    Other Study ID Numbers:
    • C-11-003
    First Posted:
    Mar 18, 2011
    Last Update Posted:
    Dec 17, 2012
    Last Verified:
    Dec 1, 2012