Comparative Study to Evaluate ISV-305 Compared to Vehicle in Blepharitis Subjects

Sponsor
Sun Pharmaceutical Industries Limited (Industry)
Overall Status
Completed
CT.gov ID
NCT01543490
Collaborator
(none)
558
Enrollment
1
Location
2
Arms
22.2
Actual Duration (Months)
25.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
558 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multicenter, Randomized, Double-Masked, Parallel-Group, Comparative Study to Evaluate the Clinical Efficacy and Safety of ISV-305 (0.1% Dexamethasone) Compared to Vehicle in the Treatment of Subjects With Blepharitis
Actual Study Start Date :
Mar 30, 2018
Actual Primary Completion Date :
Feb 4, 2020
Actual Study Completion Date :
Feb 4, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: ISV-305

0.1% dexamethasone in DuraSite® 2

Drug: ISV-305
Dexamethasone in DuraSite® 2 twice daily for 2 weeks

Placebo Comparator: Vehicle

DuraSite® 2 vehicle

Other: Vehicle
Vehicle twice daily for 2 weeks

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year and Older
Sexes Eligible for Study:
All
Accepts 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 exclusion criteria also apply

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Clinical Research CenterNewport BeachCaliforniaUnited States92663

Sponsors and Collaborators

  • Sun Pharmaceutical Industries Limited

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Sun Pharmaceutical Industries Limited
ClinicalTrials.gov Identifier:
NCT01543490
Other Study ID Numbers:
  • C-12-305-001
First Posted:
Mar 5, 2012
Last Update Posted:
Nov 19, 2021
Last Verified:
Nov 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleISV-305Vehicle
Arm/Group DescriptionISV-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.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.
Period Title: Overall Study
STARTED368190
COMPLETED352185
NOT COMPLETED165

Baseline Characteristics

Arm/Group TitleISV-305VehicleTotal
Arm/Group DescriptionISV-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.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.Total of all reporting groups
Overall Participants368190558
Age, Customized (Count of Participants)
< 17 years
0
0%
0
0%
0
0%
17 to < 65 years
146
39.7%
66
34.7%
212
38%
≥ 65 years
222
60.3%
124
65.3%
346
62%
Sex: Female, Male (Count of Participants)
Female
209
56.8%
107
56.3%
316
56.6%
Male
159
43.2%
83
43.7%
242
43.4%
Race/Ethnicity, Customized (Count of Participants)
African American or Black
20
5.4%
2
1.1%
22
3.9%
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
6
1.6%
3
1.6%
9
1.6%
White
334
90.8%
184
96.8%
518
92.8%
Native Hawaiian or Other Pacific Islander
2
0.5%
0
0%
2
0.4%
Mixed
1
0.3%
0
0%
1
0.2%
Other
5
1.4%
1
0.5%
6
1.1%
Region of Enrollment (Count of Participants)
United States
368
100%
190
100%
558
100%

Outcome Measures

1. Primary Outcome
TitleNumber 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
DescriptionThe 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 FrameDay 15

Outcome Measure Data

Analysis Population Description
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/Group TitleISV-305Vehicle
Arm/Group DescriptionISV-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.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.
Measure Participants353185
Responders
276
75%
129
67.9%
Non-responders
77
20.9%
56
29.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ISV-305, Vehicle
Comments
Type of Statistical Test Superiority
Comments Statistical hypotheses testing for the primary efficacy endpoint was 2-sided and performed using a significance (alpha) level of 0.05.
Statistical Test of Hypothesisp-Value0.0354
CommentsThe p-value was from a 2-sided Fisher's exact test.
MethodFisher Exact
CommentsThe point estimate of treatment effect (ISV-305 compared with Vehicle) was reported using Fisher's exact test.
Method of EstimationEstimation ParameterRisk Difference (RD)
Estimated Value8.5
Confidence Interval (2-Sided) 95%
0.2 to 16.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.03
Estimation CommentsThe risk difference was obtained by taking the difference in proportions (ISV-305 minus Vehicle). A 2-sided exact unconditional 95% confidence interval (CI) was calculated.
2. Secondary Outcome
TitleNumber of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population
DescriptionComplete 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 FrameDay 15

Outcome Measure Data

Analysis Population Description
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/Group TitleISV-305Vehicle
Arm/Group DescriptionISV-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.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.
Measure Participants368190
With Complete Resolution
127
34.5%
52
27.4%
Without Complete Resolution
241
65.5%
138
72.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ISV-305, Vehicle
Comments
Type of Statistical Test Superiority
Comments Statistical hypotheses testing for the secondary efficacy endpoint was 2-sided and performed using a significance (alpha) level of 0.05, and missing data imputed using the LOCF approach.
Statistical Test of Hypothesisp-Value0.1036
CommentsThe p-value was from a 2-sided Fisher's exact test.
MethodFisher Exact
CommentsThe point estimate of treatment effect (ISV-305 compared with Vehicle) was reported using Fisher's exact test.
Method of EstimationEstimation ParameterRisk Difference (RD)
Estimated Value7.1
Confidence Interval (2-Sided) 95%
-1.3 to 15.0
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.07
Estimation CommentsThe risk difference was obtained by taking the difference in proportions (ISV-305 minus Vehicle). A 2-sided exact unconditional 95% CI was calculated.

Adverse Events

Time FrameAdverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator, observed up to 41 days.
Adverse Event Reporting Description Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).
Arm/Group TitleISV-305Vehicle
Arm/Group DescriptionISV-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.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.
All Cause Mortality
ISV-305Vehicle
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/367 (0%) 0/188 (0%)
Serious Adverse Events
ISV-305Vehicle
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total4/367 (1.1%) 0/188 (0%)
Eye disorders
Retinal detachment1/367 (0.3%) 0/188 (0%)
Hepatobiliary disorders
Cholecystitis1/367 (0.3%) 0/188 (0%)
Cholelithiasis1/367 (0.3%) 0/188 (0%)
Nervous system disorders
Syncope1/367 (0.3%) 0/188 (0%)
Transient global amnesia1/367 (0.3%) 0/188 (0%)
Other (Not Including Serious) Adverse Events
ISV-305Vehicle
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total7/367 (1.9%) 5/188 (2.7%)
Eye disorders
Conjunctival hyperaemia7/367 (1.9%) 5/188 (2.7%)

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.

Results Point of Contact

Name/TitleHead-Clinical Development
OrganizationSun Pharma Advanced Research Company Limited
Phone912266455645
Emailclinical.trials@sparcmail.com
Responsible Party:
Sun Pharmaceutical Industries Limited
ClinicalTrials.gov Identifier:
NCT01543490
Other Study ID Numbers:
  • C-12-305-001
First Posted:
Mar 5, 2012
Last Update Posted:
Nov 19, 2021
Last Verified:
Nov 1, 2021