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

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ClinicalTrials.gov Identifier: NCT03192137
Recruitment Status : Completed
First Posted : June 19, 2017
Results First Posted : June 29, 2020
Last Update Posted : July 14, 2020
Sponsor:
Information provided by (Responsible Party):
InSite Vision

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Inflammation and Pain Associated With Cataract Surgery
Interventions Drug: ISV-305
Other: Vehicle
Enrollment 260
Recruitment Details  
Pre-assignment Details  
Arm/Group Title ISV-305 Vehicle
Hide Arm/Group Description ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days. Vehicle was administered as a matching topical ophthalmic formulation without dexamethasone in DuraSite® 2 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
Reason Not Completed
Adverse Event             10             11
Physician Decision             1             0
Lack of Efficacy             20             37
Withdrawal by Subject             3             3
Protocol Violation             4             3
Surgery Cancelled             4             1
Other - Various Administrative Reasons             8             3
Arm/Group Title ISV-305 Vehicle Total
Hide Arm/Group Description ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days. Vehicle was administered as a matching topical ophthalmic formulation without dexamethasone in DuraSite® 2 twice daily (one drop in the morning and one drop in the evening) for 16 days. Total of all reporting groups
Overall Number of Baseline Participants 158 80 238
Hide Baseline Analysis Population Description
Demographics were summarized for the Safety Population which included all randomized participants who received at least one dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 158 participants 80 participants 238 participants
68.0  (7.15) 68.5  (9.37) 68.2  (7.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 158 participants 80 participants 238 participants
Female
94
  59.5%
43
  53.8%
137
  57.6%
Male
64
  40.5%
37
  46.3%
101
  42.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 158 participants 80 participants 238 participants
American Indian or Alaska Native
1
   0.6%
0
   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%
0
   0.0%
Black or African American
10
   6.3%
5
   6.3%
15
   6.3%
White
141
  89.2%
72
  90.0%
213
  89.5%
Mixed
0
   0.0%
1
   1.3%
1
   0.4%
Other
2
   1.3%
0
   0.0%
2
   0.8%
1.Primary Outcome
Title Proportion of Participants With Anterior Chamber Cell Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.
Vehicle was administered as a matching topical ophthalmic formulation without dexamethasone in DuraSite® 2 twice daily (one drop in the morning and one drop in the evening) for 16 days.
Overall Number of Participants Analyzed 144 72
Measure Type: Number
Unit of Measure: participants
0 (did not receive rescue therapy) 69 16
0 (received rescue therapy) 0 0
1 64 30
2 5 10
3 6 12
4 0 4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ISV-305, Vehicle
Comments [Not Specified]
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
Hide 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 From baseline (Day 1) to Day 29
Hide Outcome Measure Data
Hide 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. Participants who received rescue medications were included in the mITT Population but were treated as failures.
Arm/Group Title ISV-305 Vehicle
Hide Arm/Group Description:
ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.
Vehicle was administered as a matching topical ophthalmic formulation without dexamethasone in DuraSite® 2 twice daily (one drop in the morning and one drop in the evening) for 16 days.
Overall Number of Participants Analyzed 156 77
Measure Type: Number
Unit of Measure: Participants
Pain Score of 0 on Day 1 (baseline) 103 29
Pain Score of 0 on Day 8 133 44
Pain Score of 0 on Day 15 137 49
Pain Score of 0 on Day 18 129 50
Pain Score of 0 on Day 29 135 51
Hide 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
Estimation Comments [Not Specified]
Hide 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
Estimation Comments [Not Specified]
Hide 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
Estimation Comments [Not Specified]
Hide 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
Estimation Comments [Not Specified]
Hide 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
Estimation Comments [Not Specified]
Time Frame Adverse events were reported from the date of signing the consent form to the date of completion of the participant's final visit (between 29 and 45 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., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
 
Arm/Group Title ISV-305 Vehicle
Hide Arm/Group Description ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days. Vehicle was administered as a matching topical ophthalmic formulation without dexamethasone in DuraSite® 2 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 (%) Affected / at Risk (%)
Total   0/158 (0.00%)   0/80 (0.00%) 
Hide Serious Adverse Events
ISV-305 Vehicle
Affected / at Risk (%) Affected / at Risk (%)
Total   3/158 (1.90%)   0/80 (0.00%) 
Cardiac disorders     
Atrial flutter * 1  1/158 (0.63%)  0/80 (0.00%) 
Gastrointestinal disorders     
Vomiting * 1  1/158 (0.63%)  0/80 (0.00%) 
General disorders     
Chest pain * 1  1/158 (0.63%)  0/80 (0.00%) 
Investigations     
Blood magnesium decreased * 1  1/158 (0.63%)  0/80 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary thrombosis * 1  1/158 (0.63%)  0/80 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
ISV-305 Vehicle
Affected / at Risk (%) Affected / at Risk (%)
Total   31/158 (19.62%)   22/80 (27.50%) 
Eye disorders     
Iritis * 1  6/158 (3.80%)  5/80 (6.25%) 
Visual acuity reduced * 1  7/158 (4.43%)  2/80 (2.50%) 
Eye pain * 1  3/158 (1.90%)  4/80 (5.00%) 
Cystoid macular oedema * 1  2/158 (1.27%)  3/80 (3.75%) 
Eye inflammation * 1  1/158 (0.63%)  4/80 (5.00%) 
Foreign body sensation in eyes * 1  2/158 (1.27%)  3/80 (3.75%) 
Visual impairment * 1  4/158 (2.53%)  1/80 (1.25%) 
Investigations     
Intraocular pressure increased * 1  10/158 (6.33%)  2/80 (2.50%) 
Nervous system disorders     
Headache * 1  1/158 (0.63%)  2/80 (2.50%) 
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
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.
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
Layout table for Results Point of Contact information
Name/Title: Charlotte Baenziger, Senior Director of Clinical Affairs
Organization: InSite Vision
Phone: 510-605-6007
EMail: charlotte.baenziger@sunpharma.com
Layout table for additonal information
Responsible Party: InSite Vision
ClinicalTrials.gov Identifier: NCT03192137    
Other Study ID Numbers: C-13-305-002
First Submitted: June 15, 2017
First Posted: June 19, 2017
Results First Submitted: June 10, 2020
Results First Posted: June 29, 2020
Last Update Posted: July 14, 2020