Congenital Nasolacrimal Duct Obstruction
Conditions
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.
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.
Interventions
DRUGBesivance Treatment Group
Subjects Receive Besivance™ ophthalmic suspension, 0.6% one drop in the study eye three times daily (TID) for 10 days.
DRUGPolytrim Treatment Group
Subjects receive Polytrim ophthalmic solution one drop in the study eye three times daily (TID) for 10 days.
Sponsors
Bausch & Lomb Incorporated
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Months to 12 Months
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Besivance Treatment Group Subjects received Besivance™ ophthalmic suspension, 0.6% one drop in the study eye three times daily (TID) for 10 days. | 12 |
| Polytrim Treatment Group Subjects received Polytrim ophthalmic solution one drop in the study eye three times daily (TID) for 10 days. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Polytrim Treatment Group | Besivance Treatment Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 12 Participants | 24 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 158.58 days STANDARD_DEVIATION 110.62 | 110.83 days STANDARD_DEVIATION 93.05 | 134.71 days STANDARD_DEVIATION 102.9 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 |
Outcome results
Primary
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.
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Besivance Treatment Group | 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. | Number of Treatment Success | 7 participants |
| Besivance Treatment Group | 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. | Number of Recurrence | 1 participants |
| Besivance Treatment Group | 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. | Number of Treatment Failure | 1 participants |
| Polytrim Treatment Group | 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. | Number of Treatment Success | 10 participants |
| Polytrim Treatment Group | 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. | Number of Recurrence | 1 participants |
| Polytrim Treatment Group | 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. | Number of Treatment Failure | 0 participants |
Secondary
Efficacy of Recurrence Treatment as Measured by Change in the Physician- Rated Scale of NLDO
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Besivance Treatment Group | Efficacy of Recurrence Treatment as Measured by Change in the Physician- Rated Scale of NLDO | Number of Treatment Success after Recurrence | 1 participants |
| Besivance Treatment Group | Efficacy of Recurrence Treatment as Measured by Change in the Physician- Rated Scale of NLDO | Number of Treatment Failure after Recurrence | 0 participants |
| Polytrim Treatment Group | Efficacy of Recurrence Treatment as Measured by Change in the Physician- Rated Scale of NLDO | Number of Treatment Success after Recurrence | 0 participants |
| Polytrim Treatment Group | Efficacy of Recurrence Treatment as Measured by Change in the Physician- Rated Scale of NLDO | Number of Treatment Failure after Recurrence | 1 participants |
Secondary
Medication Safety Outcomes
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 )
Population: No safety issues were reported
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Besivance Treatment Group | Medication Safety Outcomes | 0 Number of Adverse Events |
| Polytrim Treatment Group | Medication Safety Outcomes | 0 Number of Adverse Events |
Secondary
Number of Recurrences by Randomization Group
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 )
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Besivance Treatment Group | Number of Recurrences by Randomization Group | 1 Recurrence Subjects |
| Polytrim Treatment Group | Number of Recurrences by Randomization Group | 1 Recurrence Subjects |
Secondary
Treatment Failure
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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Besivance Treatment Group | Treatment Failure | 1 Number of Treatment Failures |
| Polytrim Treatment Group | Treatment Failure | 1 Number of Treatment Failures |
Post Hoc
Number of Subjects Treated Successfully at Close-Out Visit (Week 16)
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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Besivance Treatment Group | Number of Subjects Treated Successfully at Close-Out Visit (Week 16) | 8 Number of Treatment Success |
| Polytrim Treatment Group | Number of Subjects Treated Successfully at Close-Out Visit (Week 16) | 10 Number of Treatment Success |