Safety and Efficacy Study of Besivance™ for Treatment of Congenital Nasolacrimal Duct Obstruction in Children

• Sponsor: Rutgers, The State University of New Jersey (Other)
• Overall Status: Completed
• CT.gov ID: NCT01431170
• Collaborator: Bausch & Lomb Incorporated (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The goal of the study is to evaluate the application of Besivance™ (besifloxacin ophthalmic suspension, 0.6%) to treat congenital nasolacrimal duct obstruction in children. The hypothesis of the study is that Besivance™ is as safe and effective as the current standard of care for the treatment of nasolacrimal duct obstruction in children.

Condition or Disease	Intervention/Treatment	Phase
Congenital Nasolacrimal Duct Obstruction	Drug: Besivance Treatment Group; Drug: Polytrim Treatment Group	Phase 1

Detailed Description

The primary objective of this study is to evaluate the safety and efficacy of Besivance™ as an antibiotic treatment for congenital nasolacrimal duct obstruction with infection in children. The primary outcome measure is the change from baseline on the physician rated scale of Nasolacrimal Duct Obstruction (NLDO)with infection to follow-up visit #2 (Week 8) or at the time of treatment failure, if earlier.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Prospective, Double-Blinded, Parallel-Group, Randomized Study to Assess the Safety and Efficacy of Besivance™ for Treatment of Congenital Nasolacrimal Duct Obstruction in Children
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Besivance Treatment Group Besivance™ ophthalmic suspension, 0.6%	Drug: Besivance Treatment Group; Subjects Receive Besivance™ ophthalmic suspension, 0.6% one drop in the study eye three times daily (TID) for 10 days.; Other Names: Besifloxacin,Besivance
Active Comparator: Polytrim Treatment Group Polytrim ophthalmic solution	Drug: Polytrim Treatment Group; Subjects receive Polytrim ophthalmic solution one drop in the study eye three times daily (TID) for 10 days.; Other Names: polymyxin b/trimethoprim - ophthalmic

Outcome Measures

Primary Outcome Measures

1. Change in Physician-rated Scale of NLDO From Baseline to Follow-Up Visit at Week 8 or From Baseline to Time of Treatment Failure, if Earlier. [Baseline to Week 8]

   The NLDO grading scale in the study eye at every visit. The scale ranges from 0 to +4: 0: No tearing and discharge. 1: Tearing, moderate mucous discharge around nasolacrimal punctum 2: Moderate redness of the medial eyelid with mucous discharge 3: Redness and swelling of the eyelid with mucopurulent discharge 4: Redness and swelling of eyelid with purulent discharge Due to varying baseline severity (measured by NLDO grade) among subjects, change from baseline to week 8 in NLDO grade was further classified as the following: Treatment success: grade of 0 or improvement by 2 or more compared to the prior visit. Recurrence: NLDO with infection returns in the study eye, as indicated by a NLDO grade >0 after a grade of 0 at the prior visit. Treatment Failure: grade is worse than or same as the baseline visit.

Secondary Outcome Measures

1. Number of Recurrences by Randomization Group [Baseline to Week 16 (Closeout Visit )]

   Recurrence is defined as when the NLDO with infection in the subject's study eye returns, as indicated by a NLDO grading scale of greater than zero after achieving a grade of zero at the previous visit. Number of subjects who had a recurrence event of the subjects who completed the study by treatment Group.

2. Efficacy of Recurrence Treatment as Measured by Change in the Physician- Rated Scale of NLDO [Baseline to Week 16 (Closeout Visit)]

   Subjects who experience recurrence were re-treated as if they were a new patient, with the same study medication, were followed up then classified as "Treatment Success" or "Treatment Failure" according to study protocol.

3. Treatment Failure [Baseline to the time of failure or Week 16 (Closeout Visit)]

   Possible treatment failure at a follow-up examination is operationally defined as follows: if the physician-grading scale of NLDO is worse than or same as the prior visit at any given follow-up visit, possible treatment failure then exists. Treatment Failure occurred if at visit #1 (2-week visit), the physician-grading scale of NLDO is worse than or same as the baseline visit. Treatment failure can also occur at recurrence visit #1 if the NLDO grading scale is worse or the same as compared to the previous visit. Subjects who meet the criteria for treatment failure were withdrawn from the study by the principal investigator and no additional data was collected. Subjects were referred for continued care.

4. Medication Safety Outcomes [Baseline to Week 16 (Closeout Visit )]

   During each study visit, the Principal Investigator will evaluate any possible adverse events by assessing clinical complaints and symptoms that are experienced by subjects and observed by the parent(s)/legal guardian(s), including findings in external, lacrimal duct system and anterior segment using slit lamp and fundus exam using indirect ophthalmoscope by principal investigator, as well as clinical signs including findings in external, nasolacrimal duct system and anterior segment using slit lamp and fundus exam using indirect ophthalmoscope by principal investigator.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 12 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Persons who have been diagnosed with congenital Nasolacrimal Duct Obstruction (NLDO) with infection by the Principal Investigator

• Both males and females

• Persons who are age of 1 to 12 months at time of diagnosis (time of diagnosis is defined as when the Principal Investigator makes clinical diagnosis.)

Exclusion Criteria:

• Persons who have received any antibiotic treatment for NLDO with infection for more than 2 week in the past 4 weeks.

• Persons who are currently receiving systemic antibiotic treatment that cannot be discontinued.

• Persons with any other ocular anomalies that could potentially interfere with interpretation of study results.

• Persons who have had any prior nasolacrimal duct system procedures such as stenting or probing.

• Persons who have previously participated in any clinical trial(s) of Besivance™

• Persons who have participated in any other clinical trial(s) of any investigational agent(s) within 30 days prior to the Baseline visit

• Persons who have any chronic diseases that might interfere with study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of Ophthalmology and Visual Science, RUTGERS-New Jersey Medical School	Newark	New Jersey	United States	07103

Sponsors and Collaborators

• Rutgers, The State University of New Jersey
• Bausch & Lomb Incorporated

Investigators

• Principal Investigator: Suqin Guo, M.D., Institute of Ophthalmology and Visual Science, RUTGERS-New Jersey Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT01431170
• Other Study ID Numbers: 0120110184
• First Posted: Sep 9, 2011
• Last Update Posted: Jul 14, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Lacrimal Duct Obstruction; Trimethoprim; Polymyxins; Polymyxin B; Besifloxacin; Fluoroquinolones

Study Results

Participant Flow

Arm/Group Title	Besivance Treatment Group	Polytrim Treatment Group
Arm/Group Description	Subjects receive Besivance™ ophthalmic suspension, 0.6% one drop in the study eye three times daily for 10 days.	Subjects receive Polytrim ophthalmic solution one drop in the study eye three times daily for 10 days.
Period Title: Overall Study
STARTED	12	12
COMPLETED	9	11
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Besivance Treatment Group	Polytrim Treatment Group	Total
Arm/Group Description	Subjects received Besivance™ ophthalmic suspension, 0.6% one drop in the study eye three times daily (TID) for 10 days.	Subjects received Polytrim ophthalmic solution one drop in the study eye three times daily (TID) for 10 days.	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	12 100%	12 100%	24 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	110.83 (93.05)	158.58 (110.62)	134.71 (102.90)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	8 66.7%	13 54.2%
Male	7 58.3%	4 33.3%	11 45.8%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Change in Physician-rated Scale of NLDO From Baseline to Follow-Up Visit at Week 8 or From Baseline to Time of Treatment Failure, if Earlier.
Description	The NLDO grading scale in the study eye at every visit. The scale ranges from 0 to +4: 0: No tearing and discharge. 1: Tearing, moderate mucous discharge around nasolacrimal punctum 2: Moderate redness of the medial eyelid with mucous discharge 3: Redness and swelling of the eyelid with mucopurulent discharge 4: Redness and swelling of eyelid with purulent discharge Due to varying baseline severity (measured by NLDO grade) among subjects, change from baseline to week 8 in NLDO grade was further classified as the following: Treatment success: grade of 0 or improvement by 2 or more compared to the prior visit. Recurrence: NLDO with infection returns in the study eye, as indicated by a NLDO grade >0 after a grade of 0 at the prior visit. Treatment Failure: grade is worse than or same as the baseline visit.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Besivance Treatment Group	Polytrim Treatment Group
Arm/Group Description	Subjects received Besivance ophthalmic solution in the study eye, one drop three times a day for ten days	Subjects received Polytrim ophthalmic solution in the study eye, one drop three times daily for ten days.
Measure Participants	9	11
Number of Treatment Success	7 58.3%	10 83.3%
Number of Recurrence	1 8.3%	1 8.3%
Number of Treatment Failure	1 8.3%	0 0%

2. Secondary Outcome

Title	Number of Recurrences by Randomization Group
Description	Recurrence is defined as when the NLDO with infection in the subject's study eye returns, as indicated by a NLDO grading scale of greater than zero after achieving a grade of zero at the previous visit. Number of subjects who had a recurrence event of the subjects who completed the study by treatment Group.
Time Frame	Baseline to Week 16 (Closeout Visit )

Outcome Measure Data

Analysis Population Description

The overall study recurrence rate was 10% study-wide (2 of 20 subjects), with one Besivance subject (11%), and one Polytrim subject (9%) experiencing recurrence.

Arm/Group Title	Besivance Treatment Group	Polytrim Treatment Group
Arm/Group Description	Number of subjects who had a recurrence randomized to the Besivance treatment group.	Number of subjects who had a recurrence randomized to the Polytrim treatment group,
Measure Participants	9	11
Number [Recurrence Subjects]	1	1

3. Secondary Outcome

Title	Efficacy of Recurrence Treatment as Measured by Change in the Physician- Rated Scale of NLDO
Description	Subjects who experience recurrence were re-treated as if they were a new patient, with the same study medication, were followed up then classified as "Treatment Success" or "Treatment Failure" according to study protocol.
Time Frame	Baseline to Week 16 (Closeout Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Efficacy of Besivance Treatment Group	Efficacy of Polytrim Treatment Group
Arm/Group Description	Number of subjects who had a recurrence randomized to the Besivance treatment group.	Number of subjects who had a recurrence randomized to the Polytrim treatment group,
Measure Participants	1	1
Number of Treatment Success after Recurrence	1 8.3%	0 0%
Number of Treatment Failure after Recurrence	0 0%	1 8.3%

4. Secondary Outcome

Title	Treatment Failure
Description	Possible treatment failure at a follow-up examination is operationally defined as follows: if the physician-grading scale of NLDO is worse than or same as the prior visit at any given follow-up visit, possible treatment failure then exists. Treatment Failure occurred if at visit #1 (2-week visit), the physician-grading scale of NLDO is worse than or same as the baseline visit. Treatment failure can also occur at recurrence visit #1 if the NLDO grading scale is worse or the same as compared to the previous visit. Subjects who meet the criteria for treatment failure were withdrawn from the study by the principal investigator and no additional data was collected. Subjects were referred for continued care.
Time Frame	Baseline to the time of failure or Week 16 (Closeout Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Besivance Treatment Group	Polytrim Treatment Group
Arm/Group Description	Number of Treatment Failures for subjects randomized to the Besivance treatment group.	Number of Treatment Failures for subjects randomized to the Polytrim treatment group.
Measure Participants	9	11
Number [Number of Treatment Failures]	1	1

5. Secondary Outcome

Title	Medication Safety Outcomes
Description	During each study visit, the Principal Investigator will evaluate any possible adverse events by assessing clinical complaints and symptoms that are experienced by subjects and observed by the parent(s)/legal guardian(s), including findings in external, lacrimal duct system and anterior segment using slit lamp and fundus exam using indirect ophthalmoscope by principal investigator, as well as clinical signs including findings in external, nasolacrimal duct system and anterior segment using slit lamp and fundus exam using indirect ophthalmoscope by principal investigator.
Time Frame	Baseline to Week 16 (Closeout Visit )

Outcome Measure Data

Analysis Population Description

No safety issues were reported

Arm/Group Title	Besivance Safety Outcomes	Polytrim Safety Outcomes
Arm/Group Description	Number of reported medication safety issues in the Besivance Treatment Group.	Number of reported medication safety issues in the Polytrim Treatment Group
Measure Participants	9	11
Number [Number of Adverse Events]	0	0

6. Post-Hoc Outcome

Title	Number of Subjects Treated Successfully at Close-Out Visit (Week 16)
Description	Treatment Success is defined as a grade of 0 or improvement by 2 or more compared to the prior visit.
Time Frame	Baseline to Week 16 (Close-Out Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Besivance Treatment Group	Polytrim Treatment Group
Arm/Group Description	Number of subjects treated with Besivance™ ophthalmic suspension, 0.6%, who achieved treatment success by the study close-out visit (week 16).	Number of subjects treated with Polytrim ophthalmic solution, who achieved treatment success by the study close-out visit (week 16).
Measure Participants	9	11
Number [Number of Treatment Success]	8	10

Adverse Events

Time Frame	Baseline to Closeout Visit (Week 16)
Arm/Group Title	Besivance Treatment Group		Polytrim Treatment Group
Arm/Group Description	Subjects randomized to the Besivance treatment group.		Subjects randomized to the Polytrim treatment group.
All Cause Mortality
	Besivance Treatment Group		Polytrim Treatment Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Besivance Treatment Group		Polytrim Treatment Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Besivance Treatment Group		Polytrim Treatment Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/11 (0%)

Limitations/Caveats

Limitations include the small sample size which was reduced by participant drop out.We enrolled 24 subjects, completed and collected primary outcome measure data on 20.The recurrence rate was low at 10% (2 subjects), limiting secondary data analysis.

More Information

Certain Agreements

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

There is NOT 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.