Nepafenac Compared to Placebo for Ocular Pain and Inflammation

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01426854
• Collaborator: (none)
• Enrollment: 260
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 28.8

Study Details

Study Description

Brief Summary

The purpose of this study was to demonstrate that Nepafenac Ophthalmic Suspension, 0.1% is superior to Nepafenac Vehicle (placebo) for the prevention and treatment of ocular inflammation and pain associated with cataract surgery in Chinese subjects.

Condition or Disease	Intervention/Treatment	Phase
Cataract	Drug: Nepafenac Ophthalmic Suspension, 0.1%; Other: Nepafenac Vehicle Ophthalmic Solution	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical Evaluation of Safety and Efficacy of Nepafenac Ophthalmic Suspension, 0.1% Compared to Placebo for the Prevention and Treatment of Ocular Inflammation and Pain Associated With Cataract Surgery in Adult Chinese Subjects
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nepafenac Nepafenac Ophthalmic Suspension, 0.1%, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.	Drug: Nepafenac Ophthalmic Suspension, 0.1%; Topical ocular administration
Placebo Comparator: Placebo Nepafenac Vehicle, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.	Other: Nepafenac Vehicle Ophthalmic Solution; Inactive ingredients used as placebo; topical ocular administration

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects With Clinical Cure at Day 14 [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. The proportion of subjects with a clinical cure is reported as percentage.

Secondary Outcome Measures

1. Proportion of Subjects Who Were Pain-Free at All Postoperative Visits [Up to Day 14]

   Ocular pain is defined as a positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching. The Investigator scored ocular pain based on the description of pain by the subject. Pain was scored on a 6-unit scale ranging from 0 (none, absence of positive sensation) to 5 (severe, subject reports intense ocular, periocular or radiating pain requiring prescription analgesic). To be considered pain-free at all post operative visits, the patient must have had a score of 0 at Days 1, 3, 7, and 14 and any unscheduled visit. The proportion of subjects who were pain-free at all post-operative visits is reported as percentage.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult Chinese subjects, 18 years of age or older, of either sex who have a cataract, and are expected to undergo cataract extraction with the implantation of a posterior chamber intraocular lens;

• Study eye of subjects, who in the opinion of the Investigator, will have improvement in best-corrected visual acuity after surgery;

• Subjects should be able to understand and sign an informed consent that has been approved by an Independent Ethics Committee;

• Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

• Use of topical ocular or systemic steroids within 14 days prior to surgery;

• Use of topical ocular or systemic non-steroidal anti-inflammatory drugs within 7 days of surgery, except an allowed daily dose of baby aspirin (81 mg);

• Subjects planning to have cataract surgery in their fellow, non-study eye prior to the 14 day postoperative study visit;

• Any intraocular inflammation or ocular pain greater than Grade 0 in the study eye that is present during the baseline slit-lamp exam;

• Women of childbearing potential (those who are not surgically sterilized or post menopausal) may not participate in the study if any of the following conditions exist:

• they are breast feeding;

• they have a positive urine pregnancy test at baseline;

• they are not willing to undergo a urine pregnancy test upon exiting the study;

• they intend to become pregnant during the duration of the study; or,

• they do not agree to using adequate birth control methods for the duration of the study.

• Any abnormality that prevents reliable tonometry;

• Planned multiple procedures during cataract/IOL implantation surgery;

• Lens pseudoexfoliation syndrome with glaucoma or zonular compromise;

• Previous ocular trauma to the operative eye;

• A history of chronic or recurrent inflammatory eye disease;

• Ocular infection or ocular pain;

• Proliferative diabetic retinopathy;

• Uncontrolled diabetes mellitus;

• Congenital ocular anomaly;

• Iris atrophy in the operative eye;

• A nonfunctional fellow eye;

• Use of an investigational intraocular lens;

• Participation in any other clinical study within 30 days before surgery;

• Known or suspected allergy or hypersensitivity to non-steroidal anti-inflammatory agents, or to any component of the study medication;

• Subjects with known bleeding tendencies, or who are receiving medications that may prolong bleeding time, may be enrolled at the physician's discretion; continuation of previous therapy for these subjects will be left to the judgment of the physician;

• The fellow eye of an individual currently or previously enrolled in the study;

• Subjects using a topical ophthalmic prostaglandin;

• Subjects, who in the opinion of the investigator, might be at increased risk of complications from topical NSAIDs;

• Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zhongshan Ophthalmic Center, Sun Yat-sen University	Guangzhou	Guangdong	China	510060

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Mandy Ye, Director, Alcon (China) Ophthalmic Product Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01426854
• Other Study ID Numbers: C-10-026
• First Posted: Sep 1, 2011
• Last Update Posted: May 13, 2013
• Last Verified: May 1, 2013

• Keywords provided by Alcon Research: Cataract Surgery; Anti-ocular Inflammation; Anti-ocular Pain
• Additional relevant MeSH terms: Cataract; Inflammation; Nepafenac; Ophthalmic Solutions

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 8 study centers in China. Chinese men or women of at least 18 years of age who needed cataract extraction with implantation of a posterior chamber intraocular lens were enrolled and randomized in a ratio of 1:1 to receive either nepafenac or placebo.
Pre-assignment Detail	This reporting group includes all enrolled participants.

Arm/Group Title	Nepafenac	Placebo
Arm/Group Description	Nepafenac Ophthalmic Suspension, 0.1%, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.	Nepafenac Vehicle, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.
Period Title: Overall Study
STARTED	131	129
COMPLETED	119	98
NOT COMPLETED	12	31

Baseline Characteristics

Arm/Group Title	Nepafenac	Placebo	Total
Arm/Group Description	Nepafenac Ophthalmic Suspension, 0.1%, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.	Nepafenac Vehicle, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.	Total of all reporting groups
Overall Participants	125	123	248
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.8 (10.62)	69.8 (10.19)	69.3 (10.40)
Age, Customized (participants) [Number]
18 to <65 years	35 28%	33 26.8%	68 27.4%
65 to <75 years	43 34.4%	44 35.8%	87 35.1%
75 to <85 years	42 33.6%	43 35%	85 34.3%
85 to <95 years	5 4%	3 2.4%	8 3.2%
Sex: Female, Male (Count of Participants)
Female	72 57.6%	72 58.5%	144 58.1%
Male	53 42.4%	51 41.5%	104 41.9%
Region of Enrollment (participants) [Number]
China	125 100%	123 100%	248 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects With Clinical Cure at Day 14
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. The proportion of subjects with a clinical cure is reported as percentage.
Time Frame	Day 14 postoperative

Outcome Measure Data

Analysis Population Description

Intent-to-treat: All randomized subjects who completed cataract/IOL implant surgery and returned for at least one postoperative primary efficacy assessment.

Arm/Group Title	Nepafenac	Placebo
Arm/Group Description	Nepafenac Ophthalmic Suspension, 0.1%, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.	Nepafenac Vehicle, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.
Measure Participants	122	122
Number [Percentage of subjects]	80.3	39.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nepafenac, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Proportion of Subjects Who Were Pain-Free at All Postoperative Visits
Description	Ocular pain is defined as a positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching. The Investigator scored ocular pain based on the description of pain by the subject. Pain was scored on a 6-unit scale ranging from 0 (none, absence of positive sensation) to 5 (severe, subject reports intense ocular, periocular or radiating pain requiring prescription analgesic). To be considered pain-free at all post operative visits, the patient must have had a score of 0 at Days 1, 3, 7, and 14 and any unscheduled visit. The proportion of subjects who were pain-free at all post-operative visits is reported as percentage.
Time Frame	Up to Day 14

Outcome Measure Data

Analysis Population Description

Intent-to-treat: All randomized subjects who completed cataract/IOL implant surgery and returned for at least one postoperative primary efficacy assessment.

Arm/Group Title	Nepafenac	Placebo
Arm/Group Description	Nepafenac Ophthalmic Suspension, 0.1%, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.	Nepafenac Vehicle, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.
Measure Participants	122	122
Number [Percentage of subjects]	71.3	40.2

Adverse Events

Time Frame	Adverse events were collected for the duration of the study. Individual adverse events were recorded from the start of study treatment. At each visit, after the subject spontaneously mentioned any problems, the study staff inquired about adverse events.
Adverse Event Reporting Description	The safety population includes all participants who received at least one dose of study drug or discontinued before surgery and failed to return the test article bottle or returned the bottle with a broken seal.
Arm/Group Title	Nepafenac		Placebo
Arm/Group Description	Nepafenac Ophthalmic Suspension, 0.1%, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.		Nepafenac Vehicle, 1 drop to the operative eye, 3 times a day, beginning 1 day preoperatively and continuing through the day of surgery and for 14 days postoperatively. An additional dose was administered prior to surgery.
All Cause Mortality
	Nepafenac		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nepafenac		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/125 (0%)		1/123 (0.8%)
Nervous system disorders
Vascular headache	0/125 (0%)		1/123 (0.8%)
Other (Not Including Serious) Adverse Events
	Nepafenac		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/125 (0%)		0/123 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Results, materials of research, relevant intellectual property, and trial materials may not be used, disclosed, revealed, or published in any form without Sponsor's prior written consent.