Trial Outcomes & Findings for Safety, Efficacy, Tolerability and Pharmacokinetics of AGN-223575 Ophthalmic Suspension in Patients With Dry Eye Disease (NCT NCT02435914)
NCT ID: NCT02435914
Last Updated: 2019-04-05
Results Overview
Nasal and temporal bulbar conjunctival hyperemia were graded separately in each eye by the investigator under slit-lamp magnification by assigning a score of 0 to 4 for each quadrant based on comparison to the Allergan Dry Eye Redness Scale with photographic reference where: 0=Normal, vessels of bulbar conjunctiva are easily observed; 1=Trace redness; 2=Mild redness; 3=Moderate redness; 4=Severe redness, and each score is associated with a reference photo. For each eye, the study quadrant was determined by the greater (more severe) of the baseline redness scores for nasal and temporal bulbar conjunctival hyperemia as assessed using the Allergan Dry Eye Redness Scale. If the temporal score was greater than the nasal score, then the temporal quadrant was the study quadrant for the eye and was used to assess primary efficacy; otherwise the nasal quadrant was the study quadrant. A negative change from baseline (less redness) indicates improvement.
COMPLETED
PHASE2
236 participants
Baseline, Day 14
2019-04-05
Participant Flow
Participant milestones
| Measure |
AGN-223575 Dose A
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
58
|
59
|
60
|
59
|
|
Overall Study
COMPLETED
|
57
|
58
|
59
|
59
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
1
|
0
|
Reasons for withdrawal
| Measure |
AGN-223575 Dose A
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
Overall Study
Ocular Adverse Event
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Overall Study
Other Miscellaneous Reason
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Safety, Efficacy, Tolerability and Pharmacokinetics of AGN-223575 Ophthalmic Suspension in Patients With Dry Eye Disease
Baseline characteristics by cohort
| Measure |
AGN-223575 Dose A
n=58 Participants
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
n=59 Participants
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
n=60 Participants
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
n=59 Participants
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
Total
n=236 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
53.9 years
STANDARD_DEVIATION 16.37 • n=93 Participants
|
59.2 years
STANDARD_DEVIATION 14.74 • n=4 Participants
|
56.6 years
STANDARD_DEVIATION 16.10 • n=27 Participants
|
54.1 years
STANDARD_DEVIATION 17.87 • n=483 Participants
|
56.0 years
STANDARD_DEVIATION 16.34 • n=36 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=93 Participants
|
47 Participants
n=4 Participants
|
39 Participants
n=27 Participants
|
46 Participants
n=483 Participants
|
168 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
13 Participants
n=483 Participants
|
68 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 14Population: Modified Intent-to-treat (mITT) population, consisted of all randomized and treated patients who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. "n" in the category is the number of participants with data available at the given time-point.
Nasal and temporal bulbar conjunctival hyperemia were graded separately in each eye by the investigator under slit-lamp magnification by assigning a score of 0 to 4 for each quadrant based on comparison to the Allergan Dry Eye Redness Scale with photographic reference where: 0=Normal, vessels of bulbar conjunctiva are easily observed; 1=Trace redness; 2=Mild redness; 3=Moderate redness; 4=Severe redness, and each score is associated with a reference photo. For each eye, the study quadrant was determined by the greater (more severe) of the baseline redness scores for nasal and temporal bulbar conjunctival hyperemia as assessed using the Allergan Dry Eye Redness Scale. If the temporal score was greater than the nasal score, then the temporal quadrant was the study quadrant for the eye and was used to assess primary efficacy; otherwise the nasal quadrant was the study quadrant. A negative change from baseline (less redness) indicates improvement.
Outcome measures
| Measure |
AGN-223575 Dose A
n=58 Participants
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
n=59 Participants
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
n=60 Participants
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
n=57 Participants
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale
Baseline
|
1.9 score on a scale
Standard Deviation 0.68
|
2.2 score on a scale
Standard Deviation 0.69
|
2.0 score on a scale
Standard Deviation 0.70
|
2.1 score on a scale
Standard Deviation 0.72
|
|
Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale
Change from Baseline at Day 14
|
-0.7 score on a scale
Standard Deviation 0.80
|
-0.9 score on a scale
Standard Deviation 0.76
|
-0.8 score on a scale
Standard Deviation 0.76
|
-0.6 score on a scale
Standard Deviation 0.84
|
SECONDARY outcome
Timeframe: Baseline, Day 14Population: mITT population, consisted of all randomized and treated participants who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. "n" in the category is the number of participants with data available at the given time-point.
OSDI questionnaire consists of 12 questions regarding ocular symptoms, environmental triggers, and vision-related functioning in patients with dry eye disease. The participants rate each question on a 5-point scale where: 0=none of the time to 4=all of the time. The scores are totaled over the 12 questions and normalized/converted to a total score of 0=no disability to 100=complete disability. Higher OSDI scores are associated with greater severity. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
AGN-223575 Dose A
n=58 Participants
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
n=59 Participants
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
n=60 Participants
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
n=59 Participants
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale
Baseline
|
49.65 score on a scale
Standard Deviation 16.510
|
51.00 score on a scale
Standard Deviation 18.908
|
48.95 score on a scale
Standard Deviation 16.472
|
52.63 score on a scale
Standard Deviation 19.204
|
|
Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale
Change from Baseline at Day 14
|
-14.64 score on a scale
Standard Deviation 16.647
|
-15.92 score on a scale
Standard Deviation 16.329
|
-15.27 score on a scale
Standard Deviation 17.305
|
-14.76 score on a scale
Standard Deviation 17.297
|
SECONDARY outcome
Timeframe: Baseline, Day 14Population: mITT population, consisted of all randomized and treated participants who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. "n" in the category is the number of participants with data available at the given time-point.
The cornea is the transparent front part of the eye which covers the iris and pupil. Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale where: 0=no staining to 5=diffuse staining. The higher the grade score, the worse the dry eye severity. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
AGN-223575 Dose A
n=58 Participants
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
n=59 Participants
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
n=60 Participants
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
n=59 Participants
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale
Baseline
|
1.7 score on a scale
Standard Deviation 0.76
|
1.9 score on a scale
Standard Deviation 0.85
|
1.8 score on a scale
Standard Deviation 0.88
|
1.8 score on a scale
Standard Deviation 0.75
|
|
Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale
Change from Baseline at Day 14
|
-0.6 score on a scale
Standard Deviation 0.82
|
-0.6 score on a scale
Standard Deviation 0.80
|
-0.6 score on a scale
Standard Deviation 0.97
|
-0.5 score on a scale
Standard Deviation 0.89
|
SECONDARY outcome
Timeframe: Day 14Population: Participants from the mITT population, all randomized and treated participants who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. with data available for analysis.
A participant was considered a redness responder if the study quadrant redness score based on the Allergan Dry Eye Redness Scale in the study eye was 0=Normal (no redness).
Outcome measures
| Measure |
AGN-223575 Dose A
n=56 Participants
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
n=58 Participants
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
n=60 Participants
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
n=57 Participants
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye
Yes
|
10.7 percentage of participants
|
12.1 percentage of participants
|
15.0 percentage of participants
|
10.5 percentage of participants
|
|
Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye
No
|
89.3 percentage of participants
|
87.9 percentage of participants
|
85.0 percentage of participants
|
89.5 percentage of participants
|
Adverse Events
AGN-223575 Dose A
AGN-223575 Dose B
AGN-223575 Dose C
AGN-223575 Vehicle
Serious adverse events
| Measure |
AGN-223575 Dose A
n=58 participants at risk
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
n=59 participants at risk
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
n=60 participants at risk
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
n=59 participants at risk
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.7%
1/58
|
1.7%
1/59
|
0.00%
0/60
|
0.00%
0/59
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/58
|
1.7%
1/59
|
0.00%
0/60
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/58
|
0.00%
0/59
|
1.7%
1/60
|
0.00%
0/59
|
Other adverse events
| Measure |
AGN-223575 Dose A
n=58 participants at risk
1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose B
n=59 participants at risk
1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Dose C
n=60 participants at risk
1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days.
|
AGN-223575 Vehicle
n=59 participants at risk
1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days.
|
|---|---|---|---|---|
|
General disorders
Instillation site pain
|
5.2%
3/58
|
6.8%
4/59
|
6.7%
4/60
|
10.2%
6/59
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER