Safety/Efficacy of Nepafenac Punctal Plug Delivery System Compared to Placebo to Control Ocular Pain/Inflammation After Cataract

• Sponsor: Mati Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03496467
• Collaborator: (none)
• Enrollment: 56
• Locations: 3
• Arms: 2
• Actual Duration (Months): 9.4
• Patients Per Site: 18.7
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This is a Phase 2, multi-center, randomized, parallel-arm, double-masked, placebo-controlled study. One (1) to 2 days prior to their scheduled cataract surgery, each study subject will be randomized (2:1) in to one of two treatment groups: N-PPDS or p-PPDS, which are inserted in the lower punctum of the subject's scheduled surgical eye. All plugs will remain in the study subject's lower punctum for a period of 2 weeks following cataract surgery.

Condition or Disease	Intervention/Treatment	Phase
Pain; Inflammation	Combination Product: Nepafenac PPDS; Combination Product: Placebo PPDS	Phase 2

Detailed Description

This is a Phase 2, multi-center, randomized, parallel-arm, double-masked, placebo-controlled study. One (1) to 2 days prior to their scheduled cataract surgery, each study subject will be randomized (2:1) in to one of two treatment groups:

Group A: A total of 50 study subjects (50 eyes) will have an N-PPDS inserted in the lower punctum of their scheduled surgical eye.

Group B: A total of 25 study subjects (25 eyes) will have a p-PPDS inserted in the lower punctum of their scheduled surgical eye.

All plugs will remain in the study subject's lower punctum for a period of 2 weeks following cataract surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical Study Evaluating Safety and Efficacy of a Nepafenac Punctal Plug Delivery System (N-PPDS) Compared With Placebo Punctal Plug Delivery System (p-PPDS) in Controlling Post-Operative Ocular Pain and Inflammation After Routine Unilateral Cataract Surgery
• Actual Study Start Date: Mar 5, 2018
• Actual Primary Completion Date: Dec 17, 2018
• Actual Study Completion Date: Dec 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nepafenac PPDS N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone punctal plug with a drug eluting core that contains nepafenac (active)	Combination Product: Nepafenac PPDS; A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that contains nepafenac, a nonsteroidal anti-inflammatory drug.
Placebo Comparator: Placebo PPDS p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug insert that contains no active ingredient (placebo).	Combination Product: Placebo PPDS; A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that does not contain nepafenac.

Outcome Measures

Primary Outcome Measures

1. Assessment of Pain [day 14]

   Assessment of pain in subjects as measured by a scale of 0 - 5. Post-op pain scale: 0 represents absence of pain and 5 represents a definite, continuous unbearable ocular or periocular pain.

Secondary Outcome Measures

1. Assessment of Anterior Chamber Cells [day 14]

   Anterior chamber cells are assessed using a scale of 0 - 4 with 0 representing no cells seen and 4 representing >30 cells seen.

2. Assessment of Flare [day 14]

   Anterior chamber flare is assessed using a scale of 0 - 4 with 0 representing no Tyndall effect and 4 representing Tyndall effect in anterior chamber is very intense

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. A male or female subject in good general health, ≥ 22 years of age at the time of the screening visit

2. A subject with a cataract for which routine phacoemulsification extraction and implantation of an intraocular lens has been planned

3. A subject has a lower puncta that can be dilated to 1.0 mm in their scheduled surgical eye

Exclusion Criteria:

1. A subject with a history of complications, adverse events, trauma or disease in the nasolacrimal area, whether or not it was due to punctal plug wear, including but not limited to dacryocystitis, inflammation or canaliculitis in either eye

2. A subject with structural lid abnormalities (e.g., ectropion, entropion) in their schedule surgical eye

3. A subject with a puncta >0.9 mm prior to dilation in their scheduled surgical eye

4. A subject with any signs of intraocular inflammation (cells/flare) in either eye at the screening visit

5. A subject with a known sensitivity to nepafenac or any inactive ingredient of the punctum plug, silicone, fluorescein, topical anesthetic, or any other products required for study procedures or cataract surgery

6. A subject with a history of chronic/recurrent inflammatory eye disease (e.g., scleritis, uveitis, herpes keratitis) in either eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Eye Institute-Edgewood	Edgewood	Kentucky	United States	41017
2	Ophthalmic Consultants of Long Island	Garden City	New York	United States	11530
3	Kerry Solomon, MD	Mount Pleasant	South Carolina	United States	29464

Sponsors and Collaborators

• Mati Therapeutics Inc.

Investigators

• Study Director: Deepank Utkhede, Mati Therapeutics

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 27, 2018

More Information

Publications

None provided.

• Responsible Party: Mati Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03496467
• Other Study ID Numbers: NPIF-2018-01
• First Posted: Apr 12, 2018
• Last Update Posted: Oct 12, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Mati Therapeutics Inc.: Treatment of pain and inflammation after Cataract Surgery
• Additional relevant MeSH terms: Cataract; Inflammation; Nepafenac

Study Results

Participant Flow

Arm/Group Title	Nepafenac PPDS	Placebo PPDS
Arm/Group Description	N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone punctal plug with a drug eluting core that contains nepafenac (active) Nepafenac PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that contains nepafenac, a nonsteroidal anti-inflammatory drug.	p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug insert that contains no active ingredient (placebo). Placebo PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that does not contain nepafenac.
Period Title: Overall Study
STARTED	38	18
COMPLETED	34	14
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Nepafenac PPDS	Placebo PPDS	Total
Arm/Group Description	N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone punctal plug with a drug eluting core that contains nepafenac (active) Nepafenac PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that contains nepafenac, a nonsteroidal anti-inflammatory drug.	p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug insert that contains no active ingredient (placebo). Placebo PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that does not contain nepafenac.	Total of all reporting groups
Overall Participants	38	18	56
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 36.8%	6 33.3%	20 35.7%
>=65 years	24 63.2%	12 66.7%	36 64.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.2 (7.17)	67.8 (7.64)	67.4 (7.26)
Sex: Female, Male (Count of Participants)
Female	19 50%	11 61.1%	30 53.6%
Male	19 50%	7 38.9%	26 46.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 11.1%	2 3.6%
White	38 100%	15 83.3%	53 94.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 5.6%	1 1.8%
Region of Enrollment (participants) [Number]
United States	38 100%	18 100%	56 100%

Outcome Measures

1. Primary Outcome

Title	Assessment of Pain
Description	Assessment of pain in subjects as measured by a scale of 0 - 5. Post-op pain scale: 0 represents absence of pain and 5 represents a definite, continuous unbearable ocular or periocular pain.
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nepafenac PPDS	Placebo PPDS
Arm/Group Description	N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone punctal plug with a drug eluting core that contains nepafenac (active) Nepafenac PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that contains nepafenac, a nonsteroidal anti-inflammatory drug.	p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug insert that contains no active ingredient (placebo). Placebo PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that does not contain nepafenac.
Measure Participants	34	14
no pain	30 78.9%	13 72.2%
trace pain	2 5.3%	0 0%
mild pain	2 5.3%	1 5.6%
moderate pain	0 0%	0 0%
severe pain	0 0%	0 0%
intolerable pain	0 0%	0 0%

2. Secondary Outcome

Title	Assessment of Anterior Chamber Cells
Description	Anterior chamber cells are assessed using a scale of 0 - 4 with 0 representing no cells seen and 4 representing >30 cells seen.
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nepafenac PPDS	Placebo PPDS
Arm/Group Description	N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone punctal plug with a drug eluting core that contains nepafenac (active) Nepafenac PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that contains nepafenac, a nonsteroidal anti-inflammatory drug.	p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug insert that contains no active ingredient (placebo). Placebo PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that does not contain nepafenac.
Measure Participants	34	14
None: no cells seen	22 57.9%	7 38.9%
Trace: 1-5 cells seen	7 18.4%	3 16.7%
Mild: 6-15 cells seen	5 13.2%	4 22.2%
Moderate: 16-30 cells seen	0 0%	0 0%
Severe: >30 cells seen	0 0%	0 0%

3. Secondary Outcome

Title	Assessment of Flare
Description	Anterior chamber flare is assessed using a scale of 0 - 4 with 0 representing no Tyndall effect and 4 representing Tyndall effect in anterior chamber is very intense
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nepafenac PPDS	Placebo PPDS
Arm/Group Description	N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone punctal plug with a drug eluting core that contains nepafenac (active) Nepafenac PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that contains nepafenac, a nonsteroidal anti-inflammatory drug.	p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug insert that contains no active ingredient (placebo). Placebo PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that does not contain nepafenac.
Measure Participants	34	14
None: No Tyndall effect	29 76.3%	10 55.6%
Trace: Tyndall effect barely discernible	3 7.9%	1 5.6%
Mild: Tyndall effect in anterior chamber is clearly visible	2 5.3%	3 16.7%
Moderate: Tyndall effect in anterior chamber is moderately intense	0 0%	0 0%
Severe: Tyndall effect in anterior chamber is very intense. The aqueous has a white milky appearance	0 0%	0 0%

Adverse Events

Time Frame	The Nepafenac PPDS or Placebo PPDS was inserted 1-2 days prior to surgery. Subjects were followed for 14 days (+/-2 days) post op
Adverse Event Reporting Description	Subjects were asked: "Have you had any problems since your last visit?"
Arm/Group Title	Nepafenac PPDS		Placebo PPDS
Arm/Group Description	N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone punctal plug with a drug eluting core that contains nepafenac (active) Nepafenac PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that contains nepafenac, a nonsteroidal anti-inflammatory drug.		p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug insert that contains no active ingredient (placebo). Placebo PPDS: A punctal plug delivery system (PPDS) is being developed as a device that can deliver a sustained release of a drug to a specific eye. The PPDS is made up of a medical grade silicone punctal plug which holds an insert (core) that does not contain nepafenac.
All Cause Mortality
	Nepafenac PPDS		Placebo PPDS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/18 (0%)
Serious Adverse Events
	Nepafenac PPDS		Placebo PPDS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Nepafenac PPDS		Placebo PPDS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/38 (26.3%)		3/18 (16.7%)
Eye disorders
elevated IOP	3/38 (7.9%)	3	0/18 (0%)	0
iritis	2/38 (5.3%)	2	1/18 (5.6%)	1
posterior capsule rupture	0/38 (0%)	0	1/18 (5.6%)	1
Pain/irritation/inflammation	3/38 (7.9%)	3	0/18 (0%)	0
General disorders
Cavity, 3rd molar	1/38 (2.6%)	1	0/18 (0%)	0
Nervous system disorders
Headache	1/38 (2.6%)	1	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

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.