Active, Symptomatic Blepharitis
Conditions
Brief summary
The purpose of this study is to evaluate the clinical efficacy and safety of ISV-305 (Dexamethasone in DuraSite® 2) compared to Vehicle in the treatment of subjects with active, symptomatic Blepharitis.
Interventions
DRUGISV-305
Dexamethasone in DuraSite® 2 twice daily for 2 weeks
OTHERVehicle
Vehicle twice daily for 2 weeks
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are at least 1 years of age and have a clinical diagnosis of active, symptomatic blepharitis * Signature of the subject or parent(s) or legally authorized representative on the Informed Consent Form, and when appropriate the minor's assent in accordance with local regulations * Are willing and able to follow all instructions and attend all study visits (this applies to parent or caregiver for subjects too young to self-apply investigational product) * Are willing to avoid disallowed medication for the duration of the study * If female is of childbearing potential, agree to and submit a urine sample for pregnancy testing (prior to enrollment and at the end of the study) and use effective contraception for the duration of the study * Male subjects whose female partners are not post-menopausal must agree to one of the following: 1) completely abstain from sexual intercourse, 2) use a barrier method (condoms) with spermicide during sexual intercourse for the duration of the study, 3) provide documentation for having had a vasectomy (with documented infertility) * Additional inclusion criteria also apply
Exclusion criteria
* Have known sensitivity or poor tolerance to any component of the study drugs * Have had eyelid surgery in the study eye within twelve (12) months prior to Visit 1 or plan to have eyelid surgery during the study * Have an acute ocular infection (bacterial, viral or fungal) or active ocular inflammation other than blepharitis in the study eye * Have used topical medications on the eyelids or topical ophthalmic corticosteroid medications or systemic use of a corticosteroid mediation within 14 days prior to dosing and/or plan to use them throughout the duration of the study * Be currently pregnant, nursing, or planning a pregnancy; or be a woman who has a positive urine pregnancy test * Have prior (within 30 days prior to dosing) or anticipated concurrent use of an investigational drug or device * Have a condition or a situation which, in the investigator's opinion, may put the subject at increased risk, confound study data, or interfere significantly with the subject's study participation * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom | Day 15 | The clinical signs of blepharitis (eyelid swelling, eyelid redness, eyelid debris) were evaluated at every visit and scored by the investigator using a 0 to 3 grading scale (in general 0 = none, 1 = mild, 2 = moderate, and 3 = severe). The symptom of eyelid irritation was also evaluated at every visit and graded by the participant using a 0 to 3 grading scale (0 = almost none of the time - ≤ 25% of the time, 1 = occasionally - 26-50% of the time, 2 = frequently - 51-75% of the time, 3 = almost all of the time - ≥ 76% of the time). For each visit, the total clinical signs and symptom score was obtained by adding each of the individual scores for each domain (eyelid swelling, eyelid redness, eyelid debris, and eyelid irritation). Participants with a decrease in total clinical signs and symptom score at Day 15 by at least 2 units from Day 1 (baseline) with no increase in any sign and symptom were defined as Responders, and those not meeting these criteria were defined as Non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population | Day 15 | Complete resolution of eyelid irritation, which was defined as eyelid irritation with grading of 0, at Day 15 was analyzed. The symptoms of eyelid irritation were graded by the participant using a 0 to 3 grading scale, where 0 = almost none of the time - ≤ 25% of the time, 1 = occasionally - 26-50% of the time, 2 = frequently - 51-75% of the time, 3 = almost all of the time - ≥ 76% of the time. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ISV-305 ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 14 days. | 368 |
| Vehicle Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 14 days. | 190 |
| Total | 558 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Lack of Efficacy | 3 | 3 |
| Overall Study | Lost to Follow-up | 5 | 0 |
| Overall Study | Other-Various Administrative Reasons | 1 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | ISV-305 | Vehicle | Total |
|---|---|---|---|
| Age, Customized 17 to < 65 years | 146 Participants | 66 Participants | 212 Participants |
| Age, Customized < 17 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized ≥ 65 years | 222 Participants | 124 Participants | 346 Participants |
| Race/Ethnicity, Customized African American or Black | 20 Participants | 2 Participants | 22 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Mixed | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 334 Participants | 184 Participants | 518 Participants |
| Region of Enrollment United States | 368 Participants | 190 Participants | 558 Participants |
| Sex: Female, Male Female | 209 Participants | 107 Participants | 316 Participants |
| Sex: Female, Male Male | 159 Participants | 83 Participants | 242 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 367 | 0 / 188 |
| other Total, other adverse events | 7 / 367 | 5 / 188 |
| serious Total, serious adverse events | 4 / 367 | 0 / 188 |
Outcome results
Primary
Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom
The clinical signs of blepharitis (eyelid swelling, eyelid redness, eyelid debris) were evaluated at every visit and scored by the investigator using a 0 to 3 grading scale (in general 0 = none, 1 = mild, 2 = moderate, and 3 = severe). The symptom of eyelid irritation was also evaluated at every visit and graded by the participant using a 0 to 3 grading scale (0 = almost none of the time - ≤ 25% of the time, 1 = occasionally - 26-50% of the time, 2 = frequently - 51-75% of the time, 3 = almost all of the time - ≥ 76% of the time). For each visit, the total clinical signs and symptom score was obtained by adding each of the individual scores for each domain (eyelid swelling, eyelid redness, eyelid debris, and eyelid irritation). Participants with a decrease in total clinical signs and symptom score at Day 15 by at least 2 units from Day 1 (baseline) with no increase in any sign and symptom were defined as Responders, and those not meeting these criteria were defined as Non-responders.
Time frame: Day 15
Population: ITT Population, which included all randomized participants regardless of whether post-baseline measures were collected or study treatment was received. The participants only with valid measurement at Day 15 were used as the denominator for percentages (353 out of 368 participants for ISV-305 and 185 out of 190 participants in Vehicle).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ISV-305 | Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom | Responders | 276 Participants |
| ISV-305 | Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom | Non-responders | 77 Participants |
| Vehicle | Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom | Responders | 129 Participants |
| Vehicle | Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom | Non-responders | 56 Participants |
p-value: 0.035495% CI: [0.2, 16.6]Fisher Exact
Secondary
Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population
Complete resolution of eyelid irritation, which was defined as eyelid irritation with grading of 0, at Day 15 was analyzed. The symptoms of eyelid irritation were graded by the participant using a 0 to 3 grading scale, where 0 = almost none of the time - ≤ 25% of the time, 1 = occasionally - 26-50% of the time, 2 = frequently - 51-75% of the time, 3 = almost all of the time - ≥ 76% of the time.
Time frame: Day 15
Population: ITT Population, which included all randomized participants regardless of whether post-baseline measures were collected or study treatment was received. Participants with a valid post-baseline measurement on or before at Day 15 were used as the denominator for percentages (368 for ISV-305 and 190 for Vehicle).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ISV-305 | Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population | With Complete Resolution | 127 Participants |
| ISV-305 | Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population | Without Complete Resolution | 241 Participants |
| Vehicle | Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population | With Complete Resolution | 52 Participants |
| Vehicle | Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population | Without Complete Resolution | 138 Participants |
p-value: 0.103695% CI: [-1.3, 15]Fisher Exact