Confirmatory Study Nepafenac 0.3%

Sponsor
Alcon Research (Industry)
Overall Status
Completed
CT.gov ID
NCT01109173
Collaborator
(none)
2,120
Enrollment
1
Location
4
Arms

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the safety and efficacy of an investigational eye drop intended 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 Ophthalmic Suspension 0.3% Vehicle
  • Other: NEVANAC Vehicle
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
2120 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% for Prevention and Treatment of Ocular Inflammation and Pain After Cataract Surgery
Study Start Date :
Jun 1, 2010
Actual Primary Completion Date :
May 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 dose 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 dose was administered between 30-120 minutes prior to surgery.

Active Comparator: NEVANAC

Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.

Drug: Nepafenac Ophthalmic Suspension, 0.1%
Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye three times daily, for 16 days
Other Names:
  • NEVANACĀ®
  • Placebo Comparator: Nepafenac Vehicle 0.3%

    Nepafenac Ophthalmic Suspension 0.3% Vehicle, 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 dose was administered between 30-120 minutes prior to surgery.

    Other: Nepafenac Ophthalmic Suspension 0.3% Vehicle
    Nepafenac 0.3% vehicle, one drop in affected eye once daily, for 16 days. An additional dose was administered between 30-120 minutes prior to surgery.

    Placebo Comparator: NEVANAC Vehicle

    Nepafenac 0.1% vehicle, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.

    Other: NEVANAC Vehicle
    Nepafenac vehicle, one drop in affected eye three times daily, for 16 days

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Patients Cured at Day 14 [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 cells and flare.

    Secondary Outcome Measures

    1. Percentage of Patients Pain-Free at Day 14 [Day 14]

      Ocular pain as assessed by the investigator on a scale ranging from 0 (none) to 5 (severe). Pain-free was defined as a score of 0 on the investigator's assessment of ocular pain.

    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

    • Study Director: Dana Sager, MS, Alcon Research

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alcon Research
    ClinicalTrials.gov Identifier:
    NCT01109173
    Other Study ID Numbers:
    • C-09-055
    First Posted:
    Apr 23, 2010
    Last Update Posted:
    Nov 30, 2012
    Last Verified:
    Nov 1, 2012
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsPatients were randomized from 65 sites in 5 countries: US (49), Hungary (6), Italy (4), Sweden (4), and Switzerland (2).
    Pre-assignment DetailOf the 2120 enrolled participants, 78 withdrew before the start of dosing. Baseline characteristics are presented on all randomized patients with at least 1 postoperative assessment (ITT): 2022.
    Arm/Group TitleNepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.Nepafenac Ophthalmic Suspension 0.3% Vehicle, 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac 0.1% vehicle, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.
    Period Title: Overall Study
    STARTED851845211213
    COMPLETED763759110120
    NOT COMPLETED888610193

    Baseline Characteristics

    Arm/Group TitleNepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC VehicleTotal
    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 dose was administered between 30-120 minutes prior to surgery.Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.Nepafenac Ophthalmic Suspension 0.3% Vehicle, 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac 0.1% vehicle, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.Total of all reporting groups
    Overall Participants8078131972052022
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68.7
    (9.08)
    68.8
    (9.31)
    69.8
    (9.31)
    68.9
    (9.37)
    68.9
    (9.22)
    Sex: Female, Male (Count of Participants)
    Female
    465
    57.6%
    458
    56.3%
    118
    59.9%
    115
    56.1%
    1156
    57.2%
    Male
    342
    42.4%
    355
    43.7%
    79
    40.1%
    90
    43.9%
    866
    42.8%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Patients Cured at Day 14
    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 cells and flare.
    Time FrameDay 14

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with at least one postoperative assessment (ITT), last observation carried forward.
    Arm/Group TitleNepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.Nepafenac Ophthalmic Suspension 0.3% Vehicle, 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac 0.1% vehicle, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.
    Measure Participants807811197205
    Number [percentage of participants]
    68.4
    8.5%
    70.0
    8.6%
    34.0
    17.3%
    35.6
    17.4%
    2. Secondary Outcome
    TitlePercentage of Patients Pain-Free at Day 14
    DescriptionOcular pain as assessed by the investigator on a scale ranging from 0 (none) to 5 (severe). Pain-free was defined as a score of 0 on the investigator's assessment of ocular pain.
    Time FrameDay 14

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with at least one postoperative assessment (ITT), last observation carried forward.
    Arm/Group TitleNepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.Nepafenac Ophthalmic Suspension 0.3% Vehicle, 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac 0.1% vehicle, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.
    Measure Participants807811197205
    Number [percentage of participants]
    91
    11.3%
    90.9
    11.2%
    49.7
    25.2%
    56.1
    27.4%

    Adverse Events

    Time FrameAdverse events were collected for the duration of the study.
    Adverse Event Reporting Description This reporting group includes all patients who received exposure to the study medication or potential exposure to the study medication: 2042. At each study visit, the patient received an ocular exam, and any changes in ocular and systemic medications and/or systemic disease/conditions since surgery were recorded.
    Arm/Group TitleNepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac Ophthalmic Suspension, 0.1%, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.Nepafenac Ophthalmic Suspension 0.3% Vehicle, 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 dose was administered between 30-120 minutes prior to surgery.Nepafenac 0.1% vehicle, one drop in affected eye three times daily, beginning one day prior to surgery, continuing on the day of surgery, and for 14 days following surgery.
    All Cause Mortality
    Nepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC Vehicle
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Nepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC Vehicle
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total7/817 (0.9%) 3/819 (0.4%) 0/200 (0%) 0/206 (0%)
    Cardiac disorders
    Myocardial Infarction1/817 (0.1%) 0/819 (0%) 0/200 (0%) 0/206 (0%)
    Atrial Fibrillation0/817 (0%) 1/819 (0.1%) 0/200 (0%) 0/206 (0%)
    Infections and infestations
    Appendicitis1/817 (0.1%) 0/819 (0%) 0/200 (0%) 0/206 (0%)
    Sepsis0/817 (0%) 1/819 (0.1%) 0/200 (0%) 0/206 (0%)
    Injury, poisoning and procedural complications
    Injury2/817 (0.2%) 0/819 (0%) 0/200 (0%) 0/206 (0%)
    Metabolism and nutrition disorders
    Hyperkalaemia1/817 (0.1%) 0/819 (0%) 0/200 (0%) 0/206 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung Carcinoma Cell Type Unspecified Stage IV1/817 (0.1%) 0/819 (0%) 0/200 (0%) 0/206 (0%)
    Nervous system disorders
    Brain Oedema1/817 (0.1%) 0/819 (0%) 0/200 (0%) 0/206 (0%)
    Cerebrovascular Accident1/817 (0.1%) 1/819 (0.1%) 0/200 (0%) 0/206 (0%)
    Other (Not Including Serious) Adverse Events
    Nepafenac 0.3%NEVANACNepafenac Vehicle 0.3%NEVANAC Vehicle
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/817 (0%) 0/819 (0%) 0/200 (0%) 0/206 (0%)

    Limitations/Caveats

    This study excluded patients who were under the age of 18, had uncontrolled glaucoma, were at risk of developing macular edema (eg, diabetic retinopathy), or 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:
    NCT01109173
    Other Study ID Numbers:
    • C-09-055
    First Posted:
    Apr 23, 2010
    Last Update Posted:
    Nov 30, 2012
    Last Verified:
    Nov 1, 2012