Confirmatory Study Nepafenac 0.3%

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

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 Disease	Intervention/Treatment	Phase
Cataract	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

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 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: NEVANAC®
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

	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

• 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: Cataract; Nepafenac

Study Results

Participant Flow

Recruitment Details	Patients were randomized from 65 sites in 5 countries: US (49), Hungary (6), Italy (4), Sweden (4), and Switzerland (2).
Pre-assignment Detail	Of 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 Title	Nepafenac 0.3%	NEVANAC	Nepafenac Vehicle 0.3%	NEVANAC 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 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
STARTED	851	845	211	213
COMPLETED	763	759	110	120
NOT COMPLETED	88	86	101	93

Baseline Characteristics

Arm/Group Title	Nepafenac 0.3%	NEVANAC	Nepafenac Vehicle 0.3%	NEVANAC Vehicle	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 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 Participants	807	813	197	205	2022
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

Title	Percentage of Patients Cured 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 cells and flare.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

All randomized patients with at least one postoperative assessment (ITT), last observation carried forward.

Arm/Group Title	Nepafenac 0.3%	NEVANAC	Nepafenac Vehicle 0.3%	NEVANAC 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 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 Participants	807	811	197	205
Number [percentage of participants]	68.4 8.5%	70.0 8.6%	34.0 17.3%	35.6 17.4%

2. Secondary Outcome

Title	Percentage of Patients Pain-Free at Day 14
Description	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.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

All randomized patients with at least one postoperative assessment (ITT), last observation carried forward.

Arm/Group Title	Nepafenac 0.3%	NEVANAC	Nepafenac Vehicle 0.3%	NEVANAC 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 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 Participants	807	811	197	205
Number [percentage of participants]	91 11.3%	90.9 11.2%	49.7 25.2%	56.1 27.4%

Adverse Events

Time Frame	Adverse 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 Title	Nepafenac 0.3%		NEVANAC		Nepafenac Vehicle 0.3%		NEVANAC 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 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%		NEVANAC		Nepafenac Vehicle 0.3%		NEVANAC Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Nepafenac 0.3%		NEVANAC		Nepafenac Vehicle 0.3%		NEVANAC Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/817 (0.9%)		3/819 (0.4%)		0/200 (0%)		0/206 (0%)
Cardiac disorders
Myocardial Infarction	1/817 (0.1%)		0/819 (0%)		0/200 (0%)		0/206 (0%)
Atrial Fibrillation	0/817 (0%)		1/819 (0.1%)		0/200 (0%)		0/206 (0%)
Infections and infestations
Appendicitis	1/817 (0.1%)		0/819 (0%)		0/200 (0%)		0/206 (0%)
Sepsis	0/817 (0%)		1/819 (0.1%)		0/200 (0%)		0/206 (0%)
Injury, poisoning and procedural complications
Injury	2/817 (0.2%)		0/819 (0%)		0/200 (0%)		0/206 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	1/817 (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 IV	1/817 (0.1%)		0/819 (0%)		0/200 (0%)		0/206 (0%)
Nervous system disorders
Brain Oedema	1/817 (0.1%)		0/819 (0%)		0/200 (0%)		0/206 (0%)
Cerebrovascular Accident	1/817 (0.1%)		1/819 (0.1%)		0/200 (0%)		0/206 (0%)
Other (Not Including Serious) Adverse Events
	Nepafenac 0.3%		NEVANAC		Nepafenac Vehicle 0.3%		NEVANAC Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/817 (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.