Nepafenac 0.3% Two Study

• ClinicalTrials.gov Identifier: NCT01318499
• Recruitment Status: Completed
• First Posted: March 18, 2011
• Results First Posted: December 17, 2012
• Last Update Posted: December 17, 2012
• Sponsor: Alcon Research
• Information provided by (Responsible Party): Alcon Research

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cataract
• Interventions: Drug: Nepafenac Ophthalmic Suspension, 0.3%; Drug: Nepafenac Ophthalmic Suspension, 0.1%; Other: Nepafenac Vehicle 0.3%
• Enrollment: 1342

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

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
Reason Not Completed
Adverse Event	16	11	6
Pt Decision Unrelated to Adverse Event	1	1	2
Noncompliance	2	3	0
Treatment Failure	19	19	101
Protocol Violation	2	4	2
Patient Did Not Use Study Medication	18	28	14
Other	7	10	22

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 Number of Baseline Participants		512	493	252	1257
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	512 participants	493 participants	252 participants	1257 participants
		69.3 (9.26)	69.4 (9.15)	69.3 (9.6)	69.3 (9.28)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	512 participants	493 participants	252 participants	1257 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; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	512 participants	493 participants	252 participants	1257 participants
		512	493	252	1257

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.
Overall Number of Participants Analyzed	512	252
Measure Type: Number; Unit of Measure: 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.
Overall Number of Participants Analyzed	512	493
Measure Type: Number; Unit of Measure: Percentage of patients
	31.3	30.8

3. 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.
Overall Number of Participants Analyzed	512	493	252
Measure Type: Number; Unit of Measure: Percentage of patients
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

4. 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.
Overall Number of Participants Analyzed	512	493	252
Measure Type: Number; Unit of Measure: Percentage of patients
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

5. 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.
Overall Number of Participants Analyzed	512	493	252
Measure Type: Number; Unit of Measure: Percentage of patients
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

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 (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Nepafenac 0.3%	Nepafenac 0.1%	Nepafenac Vehicle 0.3%
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/522 (0.96%)	4/506 (0.79%)	0/254 (0.00%)
Cardiac disorders
Cardiac failure congestive 1 [1]	1/522 (0.19%)	0/506 (0.00%)	0/254 (0.00%)
Eye disorders
Angle closure glaucoma 1 [1]	1/522 (0.19%)	0/506 (0.00%)	0/254 (0.00%)
Lens dislocation 1 [1]	1/522 (0.19%)	0/506 (0.00%)	0/254 (0.00%)
Retinal detachment 1 [1]	1/522 (0.19%)	0/506 (0.00%)	0/254 (0.00%)
Visual acuity reduced 1 [1]	0/522 (0.00%)	1/506 (0.20%)	0/254 (0.00%)
Infections and infestations
Endophthalmitis 1 [1]	1/522 (0.19%)	0/506 (0.00%)	0/254 (0.00%)
Hypopyon 1 [1]	1/522 (0.19%)	0/506 (0.00%)	0/254 (0.00%)
Gastritis viral 1 [1]	0/522 (0.00%)	1/506 (0.20%)	0/254 (0.00%)
Injury, poisoning and procedural complications
Corneal abrasion 1 [1]	1/522 (0.19%)	0/506 (0.00%)	0/254 (0.00%)
Injury 1 [1]	0/522 (0.00%)	1/506 (0.20%)	0/254 (0.00%)
Nervous system disorders
Hypertensive encephalopathy 1 [1]	0/522 (0.00%)	1/506 (0.20%)	0/254 (0.00%)
1 Term from vocabulary, MedDRA 13.0; [1] Not related
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nepafenac 0.3%	Nepafenac 0.1%	Nepafenac Vehicle 0.3%
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/522 (0.00%)	0/506 (0.00%)	0/254 (0.00%)

Limitations and 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.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

• Name/Title: Dana Sager, Clinical Manager Group Leader
• Organization: Alcon Research
• Phone: 1-817-551-8603
• EMail: dana.sager@alconlabs.com

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01318499
• Other Study ID Numbers: C-11-003
• First Submitted: March 15, 2011
• First Posted: March 18, 2011
• Results First Submitted: November 1, 2012
• Results First Posted: December 17, 2012
• Last Update Posted: December 17, 2012