Study to Evaluate ISV-305 Compared to Vehicle for Treatment of Inflammation and Pain Associated With Cataract Surgery
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the ocular safety, tolerability, and efficacy of ISV-305 (dexamethasone in DuraSite® 2) compared with Vehicle in the treatment of inflammation and pain associated with cataract surgery.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
The purpose of this study is to evaluate the ocular safety, tolerability, and efficacy of topical administration of ISV-305 (0.1% dexamethasone in DuraSite® 2) compared with Vehicle when dosed twice daily for 1 day prior to surgery, the day of surgery and 14 days post cataract surgery.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: ISV-305 0.1% dexamethasone in DuraSite® 2 |
Drug: ISV-305
Dexamethasone in DuraSite® 2 twice daily for 16 days
|
Placebo Comparator: Vehicle DuraSite® 2 Vehicle |
Other: Vehicle
Vehicle twice daily for 16 days
|
Outcome Measures
Primary Outcome Measures
- Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population [Day 15]
Biomicroscopic measurement of anterior chamber cells was conducted in the surgery eye (study eye) by the same examiner from visit to visit whenever possible. A slit-lamp biomicroscope was used at x16 magnification with a 1 x 1 mm oblique high-intensity beam. Two cell counts were summed and divided by 2 to determine an average final anterior chamber cell count. This final cell count was converted to a grade: Grades 0, 1, 2, 3, 4 were assigned for cell counts of 0, 1 to 10, 11 to 20, 21 to 50, and > 50, respectively. If the averaged count fell between two grades, the higher grade was selected (e.g., if the two counts were 10 and 11, the average of 10.5 fell into Grade 2). Missing anterior chamber cell grade at Day 15 was imputed by last non-missing scheduled post-baseline anterior chamber cell grade assessed prior to Day 15 (last observation carried forward).
Secondary Outcome Measures
- Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment [Day 1 to Day 29]
Eye pain/discomfort in the study eye was evaluated at every visit except Visit 2 (Surgery; Day 0) using a VAS, scoring from 0 to 100 using a mark on a 100 mm line (0 = absent; 100 = maximum). Participants were asked to rate the feeling of the symptom in the study eye from absent to extreme by moving a slide on the side of the scale to align with images of descriptive faces.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Are at least 17 years of age
-
Are scheduled for uncomplicated unilateral cataract surgery
-
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
-
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 any sign of iritis or scleritis in the study eye
-
Have an acute ocular infection (bacterial, viral or fungal) or active ocular inflammation in the study eye
-
Have any active or chronic/recurrent ocular or systemic disease that is uncontrolled and likely to affect wound healing (e.g., diabetes mellitus, systemic connective tissue disease, severe atopic disease)
-
Have known blood dyscrasia or bone marrow suppression
-
Have any active corneal pathology in the study eye
-
Have had radial keratotomy, corneal transplant, or LASIK in the study eye within the last 2 years
-
Be currently pregnant, nursing, or planning a pregnancy; or have a positive urine pregnancy test
-
Have prior (within 30 days of beginning study treatment) 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
-
Use of any medication the investigator feels may interfere with the study parameters
-
Additional exclusion criteria also apply
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Clinical Research Center | Memphis | Tennessee | United States | 38120 |
Sponsors and Collaborators
- Sun Pharmaceutical Industries Limited
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- C-13-305-002
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | ISV-305 | Vehicle |
---|---|---|
Arm/Group Description | 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 16 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 16 days. |
Period Title: Overall Study | ||
STARTED | 173 | 87 |
COMPLETED | 123 | 29 |
NOT COMPLETED | 50 | 58 |
Baseline Characteristics
Arm/Group Title | ISV-305 | Vehicle | Total |
---|---|---|---|
Arm/Group Description | 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 16 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 16 days. | Total of all reporting groups |
Overall Participants | 158 | 80 | 238 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
68.0
(7.15)
|
68.5
(9.37)
|
68.2
(7.95)
|
Sex: Female, Male (Count of Participants) | |||
Female |
94
59.5%
|
43
53.8%
|
137
57.6%
|
Male |
64
40.5%
|
37
46.3%
|
101
42.4%
|
Race/Ethnicity, Customized (Count of Participants) | |||
American Indian or Alaska Native |
1
0.6%
|
0
0%
|
1
0.4%
|
Asian |
4
2.5%
|
2
2.5%
|
6
2.5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
10
6.3%
|
5
6.3%
|
15
6.3%
|
White |
141
89.2%
|
72
90%
|
213
89.5%
|
Mixed |
0
0%
|
1
1.3%
|
1
0.4%
|
Other |
2
1.3%
|
0
0%
|
2
0.8%
|
Outcome Measures
Title | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population |
---|---|
Description | Biomicroscopic measurement of anterior chamber cells was conducted in the surgery eye (study eye) by the same examiner from visit to visit whenever possible. A slit-lamp biomicroscope was used at x16 magnification with a 1 x 1 mm oblique high-intensity beam. Two cell counts were summed and divided by 2 to determine an average final anterior chamber cell count. This final cell count was converted to a grade: Grades 0, 1, 2, 3, 4 were assigned for cell counts of 0, 1 to 10, 11 to 20, 21 to 50, and > 50, respectively. If the averaged count fell between two grades, the higher grade was selected (e.g., if the two counts were 10 and 11, the average of 10.5 fell into Grade 2). Missing anterior chamber cell grade at Day 15 was imputed by last non-missing scheduled post-baseline anterior chamber cell grade assessed prior to Day 15 (last observation carried forward). |
Time Frame | Day 15 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Population - included randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment (ACC or VAS). Participants who received rescue medications were included in the mITT Population, but were treated as failures. |
Arm/Group Title | ISV-305 | Vehicle |
---|---|---|
Arm/Group Description | 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 16 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 16 days. |
Measure Participants | 144 | 72 |
0 (did not receive rescue therapy) |
69
43.7%
|
16
20%
|
0 (received rescue therapy) |
0
0%
|
0
0%
|
1 |
64
40.5%
|
30
37.5%
|
2 |
5
3.2%
|
10
12.5%
|
3 |
6
3.8%
|
12
15%
|
4 |
0
0%
|
4
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 two-sided and performed using a significance (alpha) level of 0.05. | |
Statistical Test of Hypothesis | p-Value | 0.0005 |
Comments | P-values were from a Chi-Square test (with continuity correction) of differences between treatments in the proportion of participants with anterior chamber cells Grade 0 who did not receive rescue medication versus all other grades combined. | |
Method | Chi-squared, Corrected | |
Comments | A Fisher's exact test was used if 1 or more of the cells had an expected frequency of ≤ 5. |
Title | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment |
---|---|
Description | Eye pain/discomfort in the study eye was evaluated at every visit except Visit 2 (Surgery; Day 0) using a VAS, scoring from 0 to 100 using a mark on a 100 mm line (0 = absent; 100 = maximum). Participants were asked to rate the feeling of the symptom in the study eye from absent to extreme by moving a slide on the side of the scale to align with images of descriptive faces. |
Time Frame | Day 1 to Day 29 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Population - included randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment (ACC or VAS). Participants who received rescue medications were included in the mITT Population but were treated as failures. |
Arm/Group Title | ISV-305 | Vehicle |
---|---|---|
Arm/Group Description | 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 16 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 16 days. |
Measure Participants | 156 | 77 |
Pain Score of 0 on Day 1 |
103
65.2%
|
29
36.3%
|
Pain Score of 0 on Day 8 |
133
84.2%
|
44
55%
|
Pain Score of 0 on Day 15 |
137
86.7%
|
49
61.3%
|
Pain Score of 0 on Day 18 |
129
81.6%
|
50
62.5%
|
Pain Score of 0 on Day 29 |
135
85.4%
|
51
63.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | ISV-305, Vehicle |
---|---|---|
Comments | Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 1 | |
Type of Statistical Test | Superiority | |
Comments | Statistical hypotheses testing for the secondary efficacy endpoints were two-sided and performed using a significance (alpha) level of 0.05. | |
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | P-values were from a Chi-Square test (with continuity correction). | |
Method | Chi-squared, Corrected | |
Comments | A Fisher's exact test was used if 1 or more of the cells had an expected frequency of ≤ 5. | |
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 3.217 | |
Confidence Interval |
(2-Sided) 95% 1.823 to 5.675 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | ISV-305, Vehicle |
---|---|---|
Comments | Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 8 | |
Type of Statistical Test | Superiority | |
Comments | Statistical hypotheses testing for the secondary efficacy endpoints were two-sided and performed using a significance (alpha) level of 0.05. | |
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | P-values were from a Chi-Square test (with continuity correction). | |
Method | Chi-squared, Corrected | |
Comments | A Fisher's exact test was used if 1 or more of the cells had an expected frequency of ≤ 5. | |
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 4.337 | |
Confidence Interval |
(2-Sided) 95% 2.305 to 8.161 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | ISV-305, Vehicle |
---|---|---|
Comments | Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 15 | |
Type of Statistical Test | Superiority | |
Comments | Statistical hypotheses testing for the secondary efficacy endpoints were two-sided and performed using a significance (alpha) level of 0.05. | |
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | P-values were from a Chi-Square test (with continuity correction). | |
Method | Chi-squared, Corrected | |
Comments | A Fisher's exact test was used if 1 or more of the cells had an expected frequency of ≤ 5. | |
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 4.120 | |
Confidence Interval |
(2-Sided) 95% 2.113 to 8.033 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | ISV-305, Vehicle |
---|---|---|
Comments | Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 18 | |
Type of Statistical Test | Superiority | |
Comments | Statistical hypotheses testing for the secondary efficacy endpoints were two-sided and performed using a significance (alpha) level of 0.05. | |
Statistical Test of Hypothesis | p-Value | 0.0043 |
Comments | P-values were from a Chi-Square test (with continuity correction). | |
Method | Chi-squared, Corrected | |
Comments | A Fisher's exact test was used if 1 or more of the cells had an expected frequency of ≤ 5. | |
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 2.580 | |
Confidence Interval |
(2-Sided) 95% 1.380 to 4.822 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | ISV-305, Vehicle |
---|---|---|
Comments | Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 29 | |
Type of Statistical Test | Superiority | |
Comments | Statistical hypotheses testing for the secondary efficacy endpoints were two-sided and performed using a significance (alpha) level of 0.05. | |
Statistical Test of Hypothesis | p-Value | 0.0005 |
Comments | P-values were from a Chi-Square test (with continuity correction). | |
Method | Chi-squared, Corrected | |
Comments | A Fisher's exact test was used if 1 or more of the cells had an expected frequency of ≤ 5. | |
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 3.277 | |
Confidence Interval |
(2-Sided) 95% 1.695 to 6.335 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | Adverse 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. | |||
---|---|---|---|---|
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., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively). | |||
Arm/Group Title | ISV-305 | Vehicle | ||
Arm/Group Description | 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 16 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 16 days. | ||
All Cause Mortality |
||||
ISV-305 | Vehicle | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/158 (0%) | 0/80 (0%) | ||
Serious Adverse Events |
||||
ISV-305 | Vehicle | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/158 (1.9%) | 0/80 (0%) | ||
Cardiac disorders | ||||
Atrial flutter | 1/158 (0.6%) | 0/80 (0%) | ||
Gastrointestinal disorders | ||||
Vomiting | 1/158 (0.6%) | 0/80 (0%) | ||
General disorders | ||||
Chest pain | 1/158 (0.6%) | 0/80 (0%) | ||
Investigations | ||||
Blood magnesium decreased | 1/158 (0.6%) | 0/80 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Pulmonary thrombosis | 1/158 (0.6%) | 0/80 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
ISV-305 | Vehicle | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 31/158 (19.6%) | 21/80 (26.3%) | ||
Eye disorders | ||||
Iritis | 6/158 (3.8%) | 5/80 (6.3%) | ||
Visual acuity reduced | 7/158 (4.4%) | 2/80 (2.5%) | ||
Eye pain | 3/158 (1.9%) | 4/80 (5%) | ||
Cystoid macular oedema | 2/158 (1.3%) | 3/80 (3.8%) | ||
Eye inflammation | 1/158 (0.6%) | 4/80 (5%) | ||
Foreign body sensation in eyes | 2/158 (1.3%) | 3/80 (3.8%) | ||
Visual impairment | 4/158 (2.5%) | 1/80 (1.3%) | ||
Investigations | ||||
Intraocular pressure increased | 10/158 (6.3%) | 2/80 (2.5%) | ||
Nervous system disorders | ||||
Headache | 1/158 (0.6%) | 2/80 (2.5%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The investigator agrees to submit the manuscript of any journal article, abstract or other presentation arising from an InSite Vision-sponsored clinical investigation to InSite Vision for editorial review prior to submission for publication or presentation. At the sponsor's request, if proprietary information is to be disclosed, proposed publications or presentations will be delayed until appropriate patent applications and/or legal documents of a similar nature have been filed.
Results Point of Contact
Name/Title | Senior Manager, Clinical Sciences |
---|---|
Organization | InSite Vision |
Phone | +91 9987096080 |
manjiri.desai@sparcmail.com |
- C-13-305-002