Hawaii-1: Safety and Efficacy of KPI-121 in Subjects With Postsurgical Inflammation
Sponsor
Kala Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02163824
Collaborator
(none)
380
23
4
7
16.5
2.3
Study Details
Study Description
Brief Summary
The primary purpose of this study is to determine the efficacy and safety of KPI-121 ophthalmic suspension compared to placebo in subjects who have undergone cataract surgery. The efficacy and safety of two different concentrations and two different dosing regimens of KPI-121 are also being assessed.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a Phase III, multicenter, double-masked, randomized, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of two doses and two dosing regimens of KPI-121 ophthalmic suspension versus placebo in subjects who require treatment of postoperative anterior ocular inflammation.
Approximately 500 subjects will be screened and up to 402 subjects with one study eye each will be randomized in this study at approximately 25 centers located in the United States. Subjects who experience postoperative inflammation on the first day following routine, uncomplicated, cataract surgery and who meet all other eligibility criteria will be randomized to one of four study groups (0.25% four times daily or 1.0% two times daily) or Placebo A four times daily or Placebo B two times daily. Drug product or placebo will be initiated on the day following surgery and instilled as one to two drops in the study eye according to the assigned dosing regimen for 14 days.
This study will include up to 7 clinic visits (including the surgery day) over 18 to 33 days total study duration. Visit 1 (Screening) will occur between 14 to 1 day(s) prior to surgery, and subjects who meet preoperative screening inclusion/exclusion criteria will be entered into the study. At Visit 2 (Surgery/Day 0) subjects will undergo routine cataract surgery according to the Investigator's normal procedures. Visit 3 (Randomization/Day 1) will occur on the day following surgery.
Following randomization, subjects will be instructed to return to the clinic to be evaluated at Visit 4 (Day 3 +2 day), Visit 5 (Day 8 ±1 day), and Visit 6 (Day 15 ±1 day). The last dose of study product will be administered upon completion of 14 days of evaluation. Following the End of Study Product Use Visit (Visit 6; Day 15 ±1 day), subjects will be asked to return to the clinic on Day 17-19 for Visit 7 (Follow-Up) and will be released from the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
380 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Double-Masked, Randomized, Controlled Trial of KPI-121 in Postsurgical Inflammation
Study Start Date
:
May 1, 2014
Actual Primary Completion Date
:
Dec 1, 2014
Actual Study Completion Date
:
Dec 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: KPI-121 0.25% QID KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. |
Drug: KPI-121 0.25%
KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
Other Names:
|
| Active Comparator: KPI-121 1.0% BID KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. |
Drug: KPI-121 1.0%
KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
Other Names:
|
| Placebo Comparator: Vehicle of KPI-121 0.25% Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. |
Drug: Vehicle of KPI-121 0.25%
Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.
Other Names:
|
| Placebo Comparator: Vehicle of KPI-121 1.0% Vehicle of KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. |
Drug: Vehicle of KPI-121 1.0%
Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Resolution of Anterior Chamber Cells [Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15)]
Subjects with complete resolution of anterior chamber cells (cell score = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6. 0= No cells seen 1 to 5 cells 6 to 15 cells 16 to 30 cells greater than 30 cells
- Resolution of Ocular Pain [Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15)]
Subjects with complete resolution of pain (grade = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6.
Secondary Outcome Measures
- Anterior Chamber Cell Grade at Visit 5. [Visit 5 (postoperative day 8)]
Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 5/Day 8. The difference in mean grade of AC cell count grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1 - 5 cells 6 - 15 cells 16 - 30 cells 4 = greater than 30 cells
- Anterior Chamber Cell Grade at Visit 6. [Visit 6 (postoperative day 15)]
Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 6/Day 15. The difference in mean grade of AC cell count grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1 - 5 cells 6 - 15 cells 16 - 30 cells 4 = greater than 30 cells
- Ocular Pain Grades at Day 8. [Visit 5 (postoperative day 8)]
Mean Grade of Ocular Pain (Scale 0-5) at Visit 5/Day 8. The difference in mean grade of ocular pain grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None Minimal Mild Moderate Moderately Severe Severe
- Ocular Pain Grades at Day 15. [Visit 6 (postoperative day 15)]
Mean Grade of Ocular Pain (Scale 0-5) at Visit 6/Day 15. The difference in mean grade of ocular pain grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None Minimal Mild Moderate Moderately Severe Severe
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
FURTHER STUDY DETAILS PROVIDED BY KALA PHARMACEUTICALS, INC.
Inclusion Criteria:
-
Candidates for routine, uncomplicated cataract surgery
-
In Investigator's opinion, potential postoperative Snellen Distance VA by pinhole method of at least 20/200 in study eye.
Exclusion Criteria:
-
Known hypersensitivity/contraindication to study product(s) or components.
-
History of glaucoma, IOP >21 mmHg at the screening or randomization visits, or being treated for glaucoma in either eye.
-
Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in judgment of Investigator could confound study assessments or limit compliance; severe/serious systemic disease or uncontrolled medical condition that in judgment of Investigator could confound study assessments or limit compliance; or have been exposed to an investigational drug within the 30 days prior to screening or 19 days following surgery.
-
In the opinion of Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sall Research Medical Center | Artesia | California | United States | 90701 |
| 2 | North Valley Eye Medical Group | Mission Hills | California | United States | 91345 |
| 3 | Martel Eye Medical Group | Rancho Cordova | California | United States | 95670 |
| 4 | Wolstan & Goldberg Eye Associates | Torrance | California | United States | 90505 |
| 5 | Clayton Eye Center | Morrow | Georgia | United States | 30260 |
| 6 | Price Vision Group | Indianapolis | Indiana | United States | 46260 |
| 7 | John-Kenyon American Eye Institute | New Albany | Indiana | United States | 47150 |
| 8 | Taustine Eye Center | Louisville | Kentucky | United States | 40217 |
| 9 | Tauber Eye Center | Kansas City | Missouri | United States | 64111 |
| 10 | Tekwani Vision Center | Saint Louis | Missouri | United States | 63128 |
| 11 | Ophthalmology Associates | Saint Louis | Missouri | United States | 63131 |
| 12 | Ophthalmology Consultants | Saint Louis | Missouri | United States | 63131 |
| 13 | Las Vegas Physicians Research Group | Henderson | Nevada | United States | 89052 |
| 14 | Raymond Fong, MDPC | New York | New York | United States | 10013 |
| 15 | Rochester Ophthalmological Group, PC | Rochester | New York | United States | 14618 |
| 16 | Cornerstone Eye Care | High Point | North Carolina | United States | 27262 |
| 17 | Cincinnati Eye Institute | Cincinnati | Ohio | United States | 45242 |
| 18 | The Eye Center of Columbus | Columbus | Ohio | United States | 43215 |
| 19 | Westside Research, LLC | Spartanburg | South Carolina | United States | 29306 |
| 20 | The Eye Clinic of Texas, Affiliate of Houston Eye Associates | League City | Texas | United States | 77573 |
| 21 | R&R Eye Research, LLC | San Antonio | Texas | United States | 78229 |
| 22 | Kozlovsky Delay & Winter Eye Consultants, LLC | San Antonio | Texas | United States | 78230 |
| 23 | Virginia Eye Consultants | Norfolk | Virginia | United States | 23502 |
Sponsors and Collaborators
- Kala Pharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Kala Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02163824
Other Study ID Numbers:
- KPI-121-C-001
First Posted:
Jun 16, 2014
Last Update Posted:
Jan 29, 2021
Last Verified:
Jan 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Kala Pharmaceuticals, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 |
|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. |
| Period Title: Overall Study | |||
| STARTED | 129 | 125 | 126 |
| COMPLETED | 127 | 124 | 124 |
| NOT COMPLETED | 2 | 1 | 2 |
Baseline Characteristics
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 | Total |
|---|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. | Total of all reporting groups |
| Overall Participants | 129 | 125 | 126 | 380 |
| Age (years) [Mean (Full Range) ] | ||||
| Mean (Full Range) [years] |
68.4
|
67.9
|
69.8
|
68.7
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
73
56.6%
|
75
60%
|
78
61.9%
|
226
59.5%
|
| Male |
56
43.4%
|
50
40%
|
48
38.1%
|
154
40.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
8
6.2%
|
15
12%
|
13
10.3%
|
36
9.5%
|
| Not Hispanic or Latino |
121
93.8%
|
110
88%
|
113
89.7%
|
344
90.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
21
16.3%
|
19
15.2%
|
21
16.7%
|
61
16.1%
|
| Native Hawaiian or Other Pacific Islander |
2
1.6%
|
2
1.6%
|
1
0.8%
|
5
1.3%
|
| Black or African American |
7
5.4%
|
9
7.2%
|
14
11.1%
|
30
7.9%
|
| White |
96
74.4%
|
91
72.8%
|
87
69%
|
274
72.1%
|
| More than one race |
1
0.8%
|
0
0%
|
1
0.8%
|
2
0.5%
|
| Unknown or Not Reported |
2
1.6%
|
4
3.2%
|
2
1.6%
|
8
2.1%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
129
100%
|
125
100%
|
126
100%
|
380
100%
|
Outcome Measures
| Title | Resolution of Anterior Chamber Cells |
|---|---|
| Description | Subjects with complete resolution of anterior chamber cells (cell score = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6. 0= No cells seen 1 to 5 cells 6 to 15 cells 16 to 30 cells greater than 30 cells |
| Time Frame | Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat- all subjects randomized |
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 |
|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. |
| Measure Participants | 129 | 125 | 126 |
| Count of Participants [Participants] |
48
37.2%
|
39
31.2%
|
19
15.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 1.0% BID, Vehicle of KPI-121 |
|---|---|---|
| Comments | All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided. All statistical tests employed a level of significance of alpha = 0.05. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .0024 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % of responders |
| Estimated Value | 16.1 | |
| Confidence Interval |
(2-Sided) 95% 5.9 to 26.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated Value is the between-group difference for % of responders and is expressed as a percentage. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 0.25% QID, Vehicle of KPI-121 |
|---|---|---|
| Comments | All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided. All statistical tests employed a level of significance of alpha = 0.05. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % of responders |
| Estimated Value | 22.1 | |
| Confidence Interval |
(2-Sided) 95% 11.7 to 32.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated Value is the between-group difference for % of responders and is expressed as a percentage. | |
| Title | Resolution of Ocular Pain |
|---|---|
| Description | Subjects with complete resolution of pain (grade = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6. |
| Time Frame | Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat- all subjects randomized. |
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 |
|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. |
| Measure Participants | 129 | 125 | 126 |
| Count of Participants [Participants] |
73
56.6%
|
67
53.6%
|
43
34.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 1.0% BID, Vehicle of KPI-121 |
|---|---|---|
| Comments | All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided. All statistical tests employed a level of significance of alpha = 0.05. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .0019 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % of responders |
| Estimated Value | 19.5 | |
| Confidence Interval |
(2-Sided) 95% 7.4 to 31.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated Value is the between-group difference for % of responders and is expressed as a percentage. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 0.25% QID, Vehicle of KPI-121 |
|---|---|---|
| Comments | All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided. All statistical tests employed a level of significance of alpha = 0.05. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .0003 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % of responders |
| Estimated Value | 22.5 | |
| Confidence Interval |
(2-Sided) 95% 10.6 to 34.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated Value is the between-group difference for % of responders and is expressed as a percentage. | |
| Title | Anterior Chamber Cell Grade at Visit 5. |
|---|---|
| Description | Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 5/Day 8. The difference in mean grade of AC cell count grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1 - 5 cells 6 - 15 cells 16 - 30 cells 4 = greater than 30 cells |
| Time Frame | Visit 5 (postoperative day 8) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed. |
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 |
|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. |
| Measure Participants | 128 | 125 | 125 |
| Mean (Standard Deviation) [score on a scale] |
0.7
(0.73)
|
0.9
(0.74)
|
1.0
(0.86)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 0.25% QID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between-group difference in mean AC grade at Day 8. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 1.0% BID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0440 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between-group difference in mean grade AC at Day 8. | |
| Title | Anterior Chamber Cell Grade at Visit 6. |
|---|---|
| Description | Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 6/Day 15. The difference in mean grade of AC cell count grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1 - 5 cells 6 - 15 cells 16 - 30 cells 4 = greater than 30 cells |
| Time Frame | Visit 6 (postoperative day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed. |
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 |
|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. |
| Measure Participants | 127 | 124 | 124 |
| Mean (Standard Deviation) [score on a scale] |
0.4
(.65)
|
0.5
(.69)
|
0.6
(.75)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 0.25% QID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0391 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between-group difference in mean AC grade at Day 15. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 1.0% BID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1811 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between-group difference in mean AC grade at Day 15. | |
| Title | Ocular Pain Grades at Day 8. |
|---|---|
| Description | Mean Grade of Ocular Pain (Scale 0-5) at Visit 5/Day 8. The difference in mean grade of ocular pain grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None Minimal Mild Moderate Moderately Severe Severe |
| Time Frame | Visit 5 (postoperative day 8) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed. |
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 |
|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. |
| Measure Participants | 128 | 125 | 125 |
| Mean (Standard Deviation) [score on a scale] |
0.4
(0.74)
|
0.4
(0.64)
|
0.5
(0.89)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 0.25% QID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1953 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between-group difference in mean ocular pain grade at Day 8. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 1.0% BID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0307 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between group difference of mean ocular pain grade at Day 8. | |
| Title | Ocular Pain Grades at Day 15. |
|---|---|
| Description | Mean Grade of Ocular Pain (Scale 0-5) at Visit 6/Day 15. The difference in mean grade of ocular pain grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None Minimal Mild Moderate Moderately Severe Severe |
| Time Frame | Visit 6 (postoperative day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed. |
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 |
|---|---|---|---|
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. |
| Measure Participants | 127 | 124 | 124 |
| Mean (Standard Deviation) [score on a scale] |
0.2
(0.50)
|
0.2
(0.51)
|
0.3
(0.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 0.25% QID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2589 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between-group difference on mean ocular pain score at Day 15. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | KPI-121 1.0% BID, Vehicle of KPI-121 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2132 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated value is the between-group difference in mean ocular pain score at Day 15. | |
Adverse Events
| Time Frame | Adverse events were collected from the time subjects signed the informed consent until they exited the study at the end of Visit 7 (up to Day 19). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 | |||
| Arm/Group Description | KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 0.25%: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant. Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. | |||
All Cause Mortality |
||||||
| KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/129 (0%) | 0/125 (0%) | 0/126 (0%) | |||
Serious Adverse Events |
||||||
| KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/129 (1.6%) | 1/125 (0.8%) | 2/126 (1.6%) | |||
| Cardiac disorders | ||||||
| Myocardial infarction | 0/129 (0%) | 0 | 0/125 (0%) | 0 | 1/126 (0.8%) | 1 |
| Eye disorders | ||||||
| Cystoid macular oedema | 0/129 (0%) | 0 | 0/125 (0%) | 0 | 1/126 (0.8%) | 1 |
| General disorders | ||||||
| Chest pain | 1/129 (0.8%) | 1 | 0/125 (0%) | 0 | 0/126 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 1/129 (0.8%) | 1 | 0/125 (0%) | 0 | 0/126 (0%) | 0 |
| Infections and infestations | ||||||
| Pneumonia | 0/129 (0%) | 0 | 1/125 (0.8%) | 1 | 0/126 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| KPI-121 0.25% QID | KPI-121 1.0% BID | Vehicle of KPI-121 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/129 (10.1%) | 6/125 (4.8%) | 20/126 (15.9%) | |||
| Eye disorders | ||||||
| eye pain | 2/129 (1.6%) | 2 | 1/125 (0.8%) | 1 | 5/126 (4%) | 5 |
| photophobia | 3/129 (2.3%) | 3 | 1/125 (0.8%) | 1 | 3/126 (2.4%) | 3 |
| punctate keratitis | 3/129 (2.3%) | 3 | 1/125 (0.8%) | 1 | 0/126 (0%) | 0 |
| eye inflammation | 2/129 (1.6%) | 2 | 0/125 (0%) | 0 | 4/126 (3.2%) | 4 |
| ocular discomfort | 0/129 (0%) | 0 | 0/125 (0%) | 0 | 2/126 (1.6%) | 2 |
| ocular hyperaemia | 0/129 (0%) | 0 | 0/125 (0%) | 0 | 5/126 (4%) | 5 |
| eye irritation | 1/129 (0.8%) | 1 | 1/125 (0.8%) | 1 | 3/126 (2.4%) | 3 |
| corneal oedema | 2/129 (1.6%) | 2 | 2/125 (1.6%) | 2 | 2/126 (1.6%) | 2 |
| Nervous system disorders | ||||||
| headache | 1/129 (0.8%) | 1 | 2/125 (1.6%) | 2 | 3/126 (2.4%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The agreement between the Principal Investigator and the Sponsor restricts the PI's rights to discuss or publish trial results until after the first to occur of the following: (a) publication of such multi-center clinical trial results; (b) notification by sponsor that such a multi-center clinical trial submission is no longer planned; or ( c) the eighteen ( 18) month anniversary of the completion, abandonment or termination of such multi-center clinical trial.
Results Point of Contact
| Name/Title | VP, Clinical Development |
|---|---|
| Organization | Kala Pharmaceuticals, Inc |
| Phone | |
| Results001@kalarx.com |
Responsible Party:
Kala Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02163824
Other Study ID Numbers:
- KPI-121-C-001
First Posted:
Jun 16, 2014
Last Update Posted:
Jan 29, 2021
Last Verified:
Jan 1, 2021