Nepafenac 0.3% Two Study

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

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 Disease	Intervention/Treatment	Phase
Cataract	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	Contact Alcon Call Center for Trial Locations	Fort Worth	Texas	United States	76134

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: cataract; inflammation; pain; inflammatory cells; aqueous flare
• Additional relevant MeSH terms: Cataract; Nepafenac

Study Results

Participant Flow

Recruitment Details	Patients were randomized from 37 investigational sites in the US.
Pre-assignment Detail	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

Arm/Group Title	Nepafenac 0.3%	Nepafenac 0.1%	Nepafenac Vehicle 0.3%
Arm/Group Description	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.	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
STARTED	540	534	268
COMPLETED	475	458	121
NOT COMPLETED	65	76	147

Baseline Characteristics

Arm/Group Title	Nepafenac 0.3%	Nepafenac 0.1%	Nepafenac Vehicle 0.3%	Total
Arm/Group Description	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.	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 Participants	512	493	252	1257
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

Title	Percentage of Patients Cured at Day 14, Nepafenac 0.3% vs. Nepafenac Vehicle 0.3%
Description	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

Outcome Measure Data

Analysis Population Description

All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.

Arm/Group Title	Nepafenac 0.3%	Nepafenac Vehicle 0.3%
Arm/Group Description	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.	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 Participants	512	252
Number [Percentage of patients]	64.6	25.0

2. Secondary Outcome

Title	Percentage of Patients Cured at Day 7, Nepafenac 0.3% vs. Nepafenac 0.1%
Description	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

Outcome Measure Data

Analysis Population Description

All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.

Arm/Group Title	Nepafenac 0.3%	Nepafenac 0.1%
Arm/Group Description	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.	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 Participants	512	493
Number [Percentage of patients]	31.3	30.8

3. Post-Hoc Outcome

Title	Cumulative Percent Clinical Success by Visit
Description	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

Outcome Measure Data

Analysis Population Description

All randomized patients with at least one post-operative assessment (intent-to-treat).

Arm/Group Title	Nepafenac 0.3%	Nepafenac 0.1%	Nepafenac Vehicle 0.3%
Arm/Group Description	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.	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 Participants	512	493	252
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

Title	Cumulative Percentage of Patients Cured by Visit
Description	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

Outcome Measure Data

Analysis Population Description

All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.

Arm/Group Title	Nepafenac 0.3%	Nepafenac 0.1%	Nepafenac 0.3% Vehicle
Arm/Group Description	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.	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 Participants	512	493	252
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

Title	Cumulative Percentage of Patients Pain Free by Visit
Description	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

Outcome Measure Data

Analysis Population Description

All randomized patients with at least one postoperative assessment (intent-to-treat), last observation carried forward.

Arm/Group Title	Nepafenac 0.3%	Nepafenac 0.1%	Nepafenac 0.3% Vehicle
Arm/Group Description	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.	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 Participants	512	493	252
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 Frame	Adverse 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 Title	Nepafenac 0.3%		Nepafenac 0.1%		Nepafenac Vehicle 0.3%
Arm/Group Description	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.		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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Nepafenac 0.3%		Nepafenac 0.1%		Nepafenac Vehicle 0.3%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/522 (1%)		4/506 (0.8%)		0/254 (0%)
Cardiac disorders
Cardiac failure congestive	1/522 (0.2%)		0/506 (0%)		0/254 (0%)
Eye disorders
Angle closure glaucoma	1/522 (0.2%)		0/506 (0%)		0/254 (0%)
Lens dislocation	1/522 (0.2%)		0/506 (0%)		0/254 (0%)
Retinal detachment	1/522 (0.2%)		0/506 (0%)		0/254 (0%)
Visual acuity reduced	0/522 (0%)		1/506 (0.2%)		0/254 (0%)
Infections and infestations
Endophthalmitis	1/522 (0.2%)		0/506 (0%)		0/254 (0%)
Hypopyon	1/522 (0.2%)		0/506 (0%)		0/254 (0%)
Gastritis viral	0/522 (0%)		1/506 (0.2%)		0/254 (0%)
Injury, poisoning and procedural complications
Corneal abrasion	1/522 (0.2%)		0/506 (0%)		0/254 (0%)
Injury	0/522 (0%)		1/506 (0.2%)		0/254 (0%)
Nervous system disorders
Hypertensive encephalopathy	0/522 (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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/522 (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.