Study of Difluprednate in the Treatment of Inflammation Following Ocular Surgery (ST-601A-002b)

• Sponsor: Sirion Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00430092
• Collaborator: (none)
• Enrollment: 219
• Location: 1
• Arms: 3

Study Details

Study Description

Brief Summary

The purpose of this phase III study is to determine the efficacy of difluprednate in the treatment of inflammation following ocular surgery.

Condition or Disease	Intervention/Treatment	Phase
Inflammation	Drug: Difluprednate; Drug: Difluprednate; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multicenter, Randomized, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Difluprednate in the Treatment of Inflammation Following Ocular Surgery

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Difluprednate 0.05% BID Difluprednate 0.05% 1 drop BID for 14 days	Drug: Difluprednate
Experimental: Difluprednate 0.05% QID Difluprednate 0.05% 1 drop QID for 14 days	Drug: Difluprednate
Placebo Comparator: Placebo Placebo for 14 days. Placebo was administered BID for 14 days and QID for 14 days. The outcomes of the 2 placebo groups were examined and were determined to be statistically indistinguishable so the placebo groups were pooled for comparison with the difluprednate groups.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Anterior Chamber Cell Grade of "0" on Day 8 (Difluprednate QID vs Placebo). [Day 8 (QID)]

   Measured on a 0 to 4 scale: "0" is ≤ 1 cell; "1" is 2-10 cells; "2" is 11-20 cells; "3" is 21-50 cells; "4" is > 50 cells.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All

Inclusion Criteria:

• Unilateral ocular surgery in the day prior to study enrollment.

• Anterior chamber cell grade ≥ "2" on the day after surgery (Day 1).

• Aged 2 years or older on the day of consent.

• Negative urine pregnancy test on Day 1 for postmenarchal subjects; negative urine pregnancy test for premenarchal subjects at the investigator's discretion.

• Provide signed written consent prior to entering the study or signed written consent from parent or legal guardian if subject is a minor and signed assent from minor subject, if appropriate.

Presurgical Exclusion Criteria:

• Systemic administration of any corticosteroid in the 2 weeks prior to study enrollment.

• Periocular injection in the study eye of any corticosteroid solution within 4 weeks prior to instillation of the study drug, or of any corticosteroid depot within 2 months prior to instillation of the study drug.

• Instillation of any topical ocular corticosteroid or NSAID within 24 hours prior to instillation of the study drug or during the course of the study, with the exception of presurgical administration of a topical NSAID to prevent miosis.

• Any history of glaucoma or ocular hypertension in the study eye.

• History or presence of endogenous uveitis.

• Any current corneal abrasion or ulceration.

• Any confirmed or suspected active viral, bacterial, or fungal keratoconjunctival disease.

• Allergy to similar drugs, such as other corticosteroids.

• History of steroid-related IOP increase.

• Scheduled surgery on the contralateral eye during the treatment period.

• Unwilling to discontinue use of contact lenses during the study period.

• Pregnancy or lactation.

• Participation in any study of an investigational topical or systemic new drug or device within 30 days prior to screening, or at any time during the study.

• Prior participation in the study described in this protocol.

• Unable or unwilling to give signed informed consent prior to participation in any study related procedures.

Postsurgical Exclusion Criteria:

• Ocular hemorrhage which interferes with evaluation of postsurgery inflammation.

• Injection of gas into the vitreous body during surgery.

• Presence of IOP ≥24 mm Hg on Day 1 after surgery.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Eye Care	Washington	Missouri	United States	63090

Sponsors and Collaborators

• Sirion Therapeutics, Inc.

Investigators

• Study Chair: Roger Vogel, MD, Sirion Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00430092
• Other Study ID Numbers: ST-601A-002b
• First Posted: Feb 1, 2007
• Last Update Posted: Jul 2, 2009
• Last Verified: May 1, 2009

• Additional relevant MeSH terms: Inflammation; Fluprednisolone; Difluprednate

Study Results

Participant Flow

Recruitment Details	First subject enrolled January 24, 2007 and last subject completed September 20, 2007 at 11 sites in the United States.
Pre-assignment Detail	Subjects enrolled if, 24 hours after ocular surgery, they had an anterior chamber cell grade of ≥ "2" and met the protocol inclusion and exclusion criteria.

Arm/Group Title	Difluprednate 0.05% BID	Difluprednate 0.05% QID	Placebo
Arm/Group Description	Difluprednate 0.05% 1 drop BID for 14 days	Difluprednate 0.05% 1 drop QID for 14 days	Placebo for 14 days. Placebo was administered BID for 14 days and QID for 14 days. The outcomes of the 2 placebo groups were examined and were determined to be statistically indistinguishable so the placebo groups were pooled for comparison with the difluprednate groups.
Period Title: Overall Study
STARTED	54	52	113
COMPLETED	48	48	56
NOT COMPLETED	6	4	57

Baseline Characteristics

Arm/Group Title	Difluprednate 0.05% BID	Difluprednate 0.05% QID	Placebo	Total
Arm/Group Description	Difluprednate 0.05% 1 drop BID for 14 days	Difluprednate 0.05% 1 drop QID for 14 days	Placebo for 14 days. Placebo was administered BID for 14 days and QID for 14 days. The outcomes of the 2 placebo groups were examined and were determined to be statistically indistinguishable so the placebo groups were pooled for comparison with the difluprednate groups.	Total of all reporting groups
Overall Participants	54	52	113	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.7 (0)	68.4 (0)	69.9 (0)	69.8 (0)
Sex: Female, Male (Count of Participants)
Female	30 55.6%	29 55.8%	70 61.9%	129.0 58.9%
Male	24 44.4%	23 44.2%	43 38.1%	90.0 41.1%

Outcome Measures

1. Primary Outcome

Title	Anterior Chamber Cell Grade of "0" on Day 8 (Difluprednate QID vs Placebo).
Description	Measured on a 0 to 4 scale: "0" is ≤ 1 cell; "1" is 2-10 cells; "2" is 11-20 cells; "3" is 21-50 cells; "4" is > 50 cells.
Time Frame	Day 8 (QID)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized subjects who received at least 1 administration of the study drug. Analysis of the ITT population, with LOCF for missing data, was conducted for all primary and secondary endpoints at Days 3, 8, 15, and 29.

Arm/Group Title	Difluprednate 0.05% BID	Difluprednate 0.05% QID	Placebo
Arm/Group Description	Difluprednate 0.05% 1 drop BID for 14 days	Difluprednate 0.05% 1 drop QID for 14 days	Placebo for 14 days. Placebo was administered BID for 14 days and QID for 14 days. The outcomes of the 2 placebo groups were examined and were determined to be statistically indistinguishable so the placebo groups were pooled for comparison with the difluprednate groups.
Measure Participants	0	52	113
Proportion of Subjects w/AC cell grade=0 on Day 8	0 0%	18 34.6%	7 6.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Difluprednate 0.05% QID, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mantel Haenszel
	Comments

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.