Study to Evaluate ISV-305 Compared to Vehicle for Treatment of Inflammation and Pain Associated With Cataract Surgery

Sponsor
Sun Pharmaceutical Industries Limited (Industry)
Overall Status
Completed
CT.gov ID
NCT03192137
Collaborator
(none)
260
1
2
14.5
17.9

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

Study Type:
Interventional
Actual Enrollment :
260 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Multicenter, Double-masked Study to Compare the Ocular Safety, Tolerability, and Efficacy of ISV-305 (0.1% Dexamethasone in DuraSite® 2) to DuraSite 2 Vehicle for the Treatment of Inflammation and Pain Associated With Cataract Surgery
Actual Study Start Date :
Jan 30, 2018
Actual Primary Completion Date :
Apr 17, 2019
Actual Study Completion Date :
Apr 17, 2019

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

  1. 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

  1. 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

Ages Eligible for Study:
17 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
Sun Pharmaceutical Industries Limited
ClinicalTrials.gov Identifier:
NCT03192137
Other Study ID Numbers:
  • C-13-305-002
First Posted:
Jun 19, 2017
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 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

1. Primary Outcome
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.
2. Secondary Outcome
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

[Not Specified]

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
Email manjiri.desai@sparcmail.com
Responsible Party:
Sun Pharmaceutical Industries Limited
ClinicalTrials.gov Identifier:
NCT03192137
Other Study ID Numbers:
  • C-13-305-002
First Posted:
Jun 19, 2017
Last Update Posted:
Nov 19, 2021
Last Verified:
Nov 1, 2021