Efficacy and Safety of PRO-155 Versus Nevanac in Post Phacoemulsification

• Sponsor: Laboratorios Sophia S.A de C.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01657266
• Collaborator: (none)
• Enrollment: 160
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 10

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate efficacy and safety of the ophthalmic solution PRO-155 in patients post phacoemulsification.

Condition or Disease	Intervention/Treatment	Phase
Cataract; Phacoemulsification Cataract Surgery	Drug: PRO-155; Drug: Nevanac	Phase 2

Detailed Description

Postsurgical inflammation is an inevitable condition after cataract surgery. The use of non-steroidal anti-inflammatory drugs is a safe option for treating ocular inflammation.

This is a phase II randomized double-blind clinical trial. The aim is to compare and to evaluate efficacy and safety of two ophthalmic solutions in patients post phacoemulsification. Patients will be randomized to receive either PRO-155 or Nevanac for 60 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 2 Randomized, Double-blind Clinical Trial to Evaluate Efficacy and Safety of the Ophthalmic Solution PRO-155 Versus Nevanac 0.1% Ophthalmic Solution in Post Phacoemulsification Patients
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PRO-155 Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days	Drug: PRO-155; Pre-medication (before surgery) and maintenance treatment.
Active Comparator: Nevanac Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days	Drug: Nevanac; Pre-medication (before surgery) and maintenance treatment.

Outcome Measures

Primary Outcome Measures

1. Percentage of Cellularity in Anterior Chamber [day 30]

   Change from Percentage of Cellularity in anterior chamber after 30 days of treatment.

2. Flare in Anterior Chamber [day 30]

   Percentage of Participants with flare in anterior chamber after 30 days of treatment

Secondary Outcome Measures

1. Percentage of Patients Without Ocular Pain [day 30]

   percentage of patients without pain, would be measured using the Visual Analog Pain Scale

2. Mean Aqueous Concentration of Intervention Drug [before surgery]

   a nurse was instructed to instill five drops of the research product into each patient's eye in the hour before surgery. The concentration of the drug was determined for aqueous humor sample (0.15 mL) with a 30-gauge needle on a TB syringe after completion of the paracentesis. The paracentesis was performed after first incision during the phacoemulsification.

Other Outcome Measures

1. Epithelial Defects Detected With Fluorescein [measurements will be made at days 1, 5, 7 and 30]

   The percentage of patients presenting epithelial defects with fluorescein staining will be evaluated

2. Epithelial Defects Detected With Green Lissamine [measurements will be made at days 1, 5, 7 and 30]

   the percentage of patients presenting epithelial defects evaluated with green lysine will be reported

3. Intraocular Pressure [day 30]

   Change from Baseline in the intraocular pressure after 30 days of treatment

4. Retinal Thickness [day 30 and 60]

   Change from Baseline in retinal thickness after 30 days of treatment. A third measurement will be done at 60 day after day surgery.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients older than 18 years who require cataract surgery

• Both genders

• Provide informed consent

• Normal Laboratory results

Exclusion Criteria:

• Patients with visual acuity of 20/40 or less in the contralateral eye of the surgery

• Patients with any trans-surgical complication

• Patients with a cataract >NC4, C4 or P4 classified with the system LOCS

• Patients with any active corneal pathology

• Patients under any steroidal treatment (topic, systemic or inhaled)14 days prior surgery or NSAIDs 7 days before the surgery (except low-dose aspirin)

• Patients with IOP <5 or >21 mmHg

• Patients that have ocular pain, cellularity or flare at the moment of selection

• Patients with ocular exfoliation, trauma or any inflammatory disease

• Patients with diabetic retinopathy that need treatment or uncontrolled diabetes mellitus

• Patients who are planning cataract surgery of the contralateral eye 14 days after surgery of the study eye

• Patients with history of hypersensitivity or contraindication for any drug used in the study

• Patients under anticoagulant treatment

• Contact lens users

• Pregnant patients, at risk of pregnancy or breastfeeding

• Patients without birth control treatment

• Patients with any active toxicomania (alcoholism, cigarette, cannabis or others)

• Patients who had participated in any clinical trial in the last 90 days

• Legal or mentally disabled patients who could not give informed consent

• Patients who cannot comply with all study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco	Mexico	44280

Sponsors and Collaborators

• Laboratorios Sophia S.A de C.V.

Investigators

• Study Director: Leopoldo M. Baiza-Durán, MD, Laboratorios Sophia S.A de C.V.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Palacio C, et al. Bromfenac 0.09% bioavailability in aqueous humor, prophylactic effect on cystoid macular edema, and clinical signs of ocular inflammation after phacoemulsification in a Mexican population. Clinical Ophthalmology 2016;10:233-237

Publications

None provided.

• Responsible Party: Laboratorios Sophia S.A de C.V.
• ClinicalTrials.gov Identifier: NCT01657266
• Other Study ID Numbers: SOPH155-0412/II
• First Posted: Aug 6, 2012
• Last Update Posted: Oct 30, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Laboratorios Sophia S.A de C.V.: bromfenac; nepafenac; cataract; phacoemulsification cataract surgery
• Additional relevant MeSH terms: Cataract; Nepafenac

Study Results

Participant Flow

Recruitment Details	160 subjects were recruited, 12 of whom were excluded, 10 because they did not meet the selection criteria and 2 refused to participate. The remaining 148 were randomly assigned to one of the 2 study groups, 73 to bromfenac and 75 to napaphenac.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Period Title: Overall Study
STARTED	73	75
COMPLETED	69	70
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	PRO-155	Nevanac	Total
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.	Total of all reporting groups
Overall Participants	69	70	139
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.4 (11.1)	68.0 (9.5)	67.7 (10.3)
Sex: Female, Male (Count of Participants)
Female	41 59.4%	39 55.7%	80 57.6%
Male	28 40.6%	31 44.3%	59 42.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	69 100%	70 100%	139 100%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Mexico	69 100%	70 100%	139 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Cellularity in Anterior Chamber
Description	Change from Percentage of Cellularity in anterior chamber after 30 days of treatment.
Time Frame	day 30

Outcome Measure Data

Analysis Population Description

Mexican patients patients who underwent cataract surgery in only 1 eye, by phacoemulsification with intraocular lens implantation.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
Day 1	64.2	64.3
Day 30	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Pearson´s Chi-square test
	Comments

2. Primary Outcome

Title	Flare in Anterior Chamber
Description	Percentage of Participants with flare in anterior chamber after 30 days of treatment
Time Frame	day 30

Outcome Measure Data

Analysis Population Description

Mexican patients patients who underwent cataract surgery in only 1 eye, by phacoemulsification with intraocular lens implantation.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
Day 1	31.4 45.5%	31.5 45%
Day 30	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Patients Without Ocular Pain
Description	percentage of patients without pain, would be measured using the Visual Analog Pain Scale
Time Frame	day 30

Outcome Measure Data

Analysis Population Description

Mexican patients patients who underwent cataract surgery in only 1 eye, by phacoemulsification with intraocular lens implantation.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
Day 1	6.1	5.7
Day 30	1.5	1.6

4. Secondary Outcome

Title	Mean Aqueous Concentration of Intervention Drug
Description	a nurse was instructed to instill five drops of the research product into each patient's eye in the hour before surgery. The concentration of the drug was determined for aqueous humor sample (0.15 mL) with a 30-gauge needle on a TB syringe after completion of the paracentesis. The paracentesis was performed after first incision during the phacoemulsification.
Time Frame	before surgery

Outcome Measure Data

Analysis Population Description

We enrolled patients of both sexes (aged >18 years) with a diagnosis of cataract according to the Lens Opacities Classification System III ≤ NC4, C4 and, P4 in one eye were eligible for enrollment. Eligible patients must have had a best-corrected visual acuity of 6/60 (20/200) Snellen score.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
Measure eyes	69	70
Mean (Standard Deviation) [ng/mL]	207.5 (152.3)	314.4 (146.5)

5. Other Pre-specified Outcome

Title	Epithelial Defects Detected With Fluorescein
Description	The percentage of patients presenting epithelial defects with fluorescein staining will be evaluated
Time Frame	measurements will be made at days 1, 5, 7 and 30

Outcome Measure Data

Analysis Population Description

Mexican patients patients who underwent cataract surgery in only 1 eye, by phacoemulsification with intraocular lens implantation.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
Day 1	54.4	78.5
Day 7	32.5	64.4
Day 15	15.6	36.1
Day 30	6	8.5

6. Other Pre-specified Outcome

Title	Epithelial Defects Detected With Green Lissamine
Description	the percentage of patients presenting epithelial defects evaluated with green lysine will be reported
Time Frame	measurements will be made at days 1, 5, 7 and 30

Outcome Measure Data

Analysis Population Description

Mexican patients who underwent cataract surgery in only 1 eye, by phacoemulsification with intraocular lens implantation.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
Day 1	62.5	86
Day 7	41.4	67.3
Day 15	21.6	57.4
Day 30	14.8	28.2

7. Other Pre-specified Outcome

Title	Intraocular Pressure
Description	Change from Baseline in the intraocular pressure after 30 days of treatment
Time Frame	day 30

Outcome Measure Data

Analysis Population Description

Mexican patients who underwent cataract surgery in only 1 eye, by phacoemulsification with intraocular lens implantation.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
Day 0	14.07 (1.82)	14.23 (1.90)
Day 1	14.66 (2.61)	15.83 (2.77)
Day 7	14.13 (1.97)	14.54 (1.85)
Day 15	13.81 (1.64)	13.91 (2.03)
Day 30	14.10 (1.78)	13.77 (1.97)

8. Other Pre-specified Outcome

Title	Retinal Thickness
Description	Change from Baseline in retinal thickness after 30 days of treatment. A third measurement will be done at 60 day after day surgery.
Time Frame	day 30 and 60

Outcome Measure Data

Analysis Population Description

Mexican patients who underwent cataract surgery in only 1 eye, by phacoemulsification with intraocular lens implantation.

Arm/Group Title	PRO-155	Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.	Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
Measure Participants	69	70
field A1 day 0	247.24 (32.90)	250.87 (34.42)
field A1 day 30	252.06 (24.95)	264.08 (34.10)
field A1 day 60	254.06 (2.78)	260.13 (33.93)

Adverse Events

Time Frame	Interval of 30 days of intervention in which adverse events could occur, included in the treatment period (January 2014-2015)
Adverse Event Reporting Description	During the pharmacological intervention period, in each visit, the principal investigator asked information about adverse events: Serious or No serious Severity: mild, moderate, severe relation with study drug or not
Arm/Group Title	PRO-155		Nevanac
Arm/Group Description	Bromfenac 0.09% (0.9mg/mL) Ophthalmic solution Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days PRO-155: Pre-medication (before surgery) and maintenance treatment.		Nepafenac 0.1% (1mg/mL) Ophthalmic Suspension Pre-medication: 1 drop each 15 minutes during 1 hour before surgery in the affected eye Maintenance therapy: 1 drop 3 times a day for 30 days Nevanac: Pre-medication (before surgery) and maintenance treatment.
All Cause Mortality
	PRO-155		Nevanac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PRO-155		Nevanac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		2/75 (2.7%)
Eye disorders
Rhegmatogenous retinal detachment	0/73 (0%)	0	1/75 (1.3%)	1
central retinal artery occlusion	0/73 (0%)	0	1/75 (1.3%)	1
Other (Not Including Serious) Adverse Events
	PRO-155		Nevanac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/73 (6.8%)		2/75 (2.7%)
Eye disorders
Cystoid macular edema	1/73 (1.4%)	1	0/75 (0%)	0
Traumatic corneal desepithelization	1/73 (1.4%)	1	0/75 (0%)	0
Posterior Capsular Rupture	1/73 (1.4%)	1	0/75 (0%)	0
viral conjunctivitis	1/73 (1.4%)	1	0/75 (0%)	0
Inflammatory cells in the corneal endothelium	1/73 (1.4%)	1	0/75 (0%)	0
intraocular lens exchange	0/73 (0%)	0	1/75 (1.3%)	1
Vascular disorders
fall from their own height	0/73 (0%)	0	1/75 (1.3%)	1

Limitations/Caveats

The study was performed according to the clinical protocol.

More Information

Certain Agreements

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

All the information is confidential and exclusive property of the sponsor. Information can be revealed only to my staff and regulatory agencies or ethics committee. All the information from this protocol is confidential and exclusive property of the sponsor, it can not be revealed without written consent from the sponsor.