Trial Outcomes & Findings for Evaluation of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease (NCT NCT02831387)
NCT ID: NCT02831387
Last Updated: 2018-10-11
Results Overview
Dry Eye symptoms were obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes separate Visual Analog Scales (VAS) for the frequency and the Severity of symptoms. The scores range from 0 to 100 where 0 = Rarely or Very Mild, and 100 = All the Time or Very Severe for the Frequency and Severity of the symptoms, respectively. The Global Score as reported in the Primary Outcome is obtained by taking the square root of the product of the frequency score multiplied by the severity score. Negative change from baseline indicates improvement.
TERMINATED
PHASE2
47 participants
Baseline to Day 29
2018-10-11
Participant Flow
Participant milestones
| Measure |
Placebo Ophthalmic Solution
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
24
|
|
Overall Study
COMPLETED
|
22
|
22
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Placebo Ophthalmic Solution
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Discontinued due to stock recovery
|
0
|
1
|
Baseline Characteristics
Evaluation of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease
Baseline characteristics by cohort
| Measure |
Placebo Ophthalmic Solution
n=23 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=24 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=99 Participants
|
24 participants
n=107 Participants
|
47 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to Day 29Population: The modified Intent-to-Treat Population (mITT) include all randomized subjects who have at least a baseline and one post-baseline symptom questionnaire part 1 assessment. This is the primary population for efficacy analyses and subjects are analyzed based on their randomized treatment.
Dry Eye symptoms were obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes separate Visual Analog Scales (VAS) for the frequency and the Severity of symptoms. The scores range from 0 to 100 where 0 = Rarely or Very Mild, and 100 = All the Time or Very Severe for the Frequency and Severity of the symptoms, respectively. The Global Score as reported in the Primary Outcome is obtained by taking the square root of the product of the frequency score multiplied by the severity score. Negative change from baseline indicates improvement.
Outcome measures
| Measure |
Placebo Ophthalmic Solution
n=23 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=24 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Change From Baseline (Visit 2) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire.
Baseline
|
58.821 units on a scale
Standard Deviation 17.0381
|
59.228 units on a scale
Standard Deviation 17.7064
|
|
Change From Baseline (Visit 2) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire.
Change from Baseline (Visit 2) to Day 29
|
-9.197 units on a scale
Standard Deviation 24.4776
|
-9.989 units on a scale
Standard Deviation 12.2523
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: The modified Intent-to-Treat Population (mITT) include all randomized subjects who have at least a baseline and one post-baseline symptom questionnaire part 1 assessment. This is the primary population for efficacy analyses and subjects are analyzed based on their randomized treatment.
Dry Eye symptom frequency was obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes a 100 mm horizontal Visual Analog Scale (VAS). The scores range from 0 to 100 where 0 = Rarely and 100 = All the Time. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Placebo Ophthalmic Solution
n=23 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=24 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores
Baseline
|
57.2 units on a scale
Standard Deviation 19.58
|
62.3 units on a scale
Standard Deviation 17.91
|
|
Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores
Change from Baseline (Visit 2) to Day 29
|
-5.3 units on a scale
Standard Deviation 25.45
|
-12.3 units on a scale
Standard Deviation 14.13
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: The modified Intent-to-Treat Population (mITT) include all randomized subjects who have at least a baseline and one post-baseline symptom questionnaire part 1 assessment. This is the primary population for efficacy analyses and subjects are analyzed based on their randomized treatment.
Dry Eye symptom severity was obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes a 100 mm horizontal Visual Analog Scales (VAS). The scores range from 0 to 100 where 0 = Very Mild and 100 = Very Severe. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Placebo Ophthalmic Solution
n=23 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=24 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores
Baseline
|
61.1 units on a scale
Standard Deviation 15.54
|
56.5 units on a scale
Standard Deviation 18.45
|
|
Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores
Change from Baseline (Visit 2) to Day 29
|
-13.2 units on a scale
Standard Deviation 24.70
|
-7.6 units on a scale
Standard Deviation 12.88
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: The modified Intent-to-Treat Population (mITT) include all randomized subjects who have at least a baseline and one post-baseline symptom questionnaire part 1 assessment. This is the primary population for efficacy analyses and subjects are analyzed based on their randomized treatment.
Corneal staining was performed to grade the corneal epithelial cell injury as measured by fluorescence using slit lamp examination. The staining was graded with the NEI scale. The corneal surface is divided into 5 corneal regions (1, Central; 2, Inferior; 3, Nasal; 4, Temporal; 5, Superior). The scores for each of these 5 regions ranged from 0 to 3 (0=no staining; 1=staining with low density; 2=staining with moderate density; 3=staining with severe density). The total staining score (sum of all regions, maximal score =15) is reported. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Placebo Ophthalmic Solution
n=23 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=24 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Change From Baseline to Day 29 in Fluorescein Staining of the Cornea.
Baseline
|
5.8 units on a scale
Standard Deviation 1.31
|
6.3 units on a scale
Standard Deviation 1.58
|
|
Change From Baseline to Day 29 in Fluorescein Staining of the Cornea.
Change from Baseline (Visit 2) to Day 29
|
-1.2 units on a scale
Standard Deviation 2.4
|
-0.7 units on a scale
Standard Deviation 2.68
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: The modified Intent-to-Treat Population (mITT) include all randomized subjects who have at least a baseline and one post-baseline symptom questionnaire part 1 assessment. This is the primary population for efficacy analyses and subjects are analyzed based on their randomized treatment.
Conjunctival staining was performed to grade the conjunctival epithelial cell injury as measured by Lissamine Green using slit-lamp examination. The staining was graded with the NEI scale. The bulbar conjunctival surface is divided into 6 regions (1, Temporal; 2 Temporal Superior; 3, Temporal Inferior; 4, Nasal Superior; 5, Nasal Inferior; 6, Nasal). The scores for each of these 6 regions ranged from 0 to 3 (0=no staining; 1=staining with low density; 2=staining with moderate density; 3=staining with severe density). The total staining score (sum of all regions, maximal score =18) is reported. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Placebo Ophthalmic Solution
n=23 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=24 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva.
Baseline
|
7.6 units on a scale
Standard Deviation 1.73
|
7.1 units on a scale
Standard Deviation 1.79
|
|
Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva.
Change from Baseline (Visit 2) to Day 29
|
-0.3 units on a scale
Standard Deviation 3.41
|
-0.2 units on a scale
Standard Deviation 3.78
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: The modified Intent-to-Treat Population (mITT) include all randomized subjects who have at least a baseline and one post-baseline symptom questionnaire part 1 assessment. For this outcome, only participants that completed the treatment were analyzed
Improvement in symptoms was evaluated using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes separate Visual Analog Scales (VAS) for the frequency and the Severity of symptoms. The scores range from 0 to 100 where 0 = Rarely or Very Mild, and 100 = All the Time or Very Severe for the Frequency and Severity of the symptoms, respectively. The Global Score is obtained by taking the square root of the product of the frequency score multiplied by the severity score. Lower scores indicate improvement in symptoms.
Outcome measures
| Measure |
Placebo Ophthalmic Solution
n=22 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=22 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Number of Participants With at Least 20% Improvement in Symptoms From Baseline to Day 29
|
8 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline to Day 15Population: The modified Intent-to-Treat Population (mITT) include all randomized subjects who have at least a baseline and one post-baseline symptom questionnaire part 1 assessment. This is the primary population for efficacy analyses and subjects are analyzed based on their randomized treatment.
Dry Eye symptoms were obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes separate Visual Analog Scales (VAS) for the frequency and the Severity of symptoms. The scores range from 0 to 100 where 0 = Rarely or Very Mild, and 100 = All the Time or Very Severe for the Frequency and Severity of the symptoms, respectively. The Global Score as reported in the Primary Outcome is obtained by taking the square root of the product of the frequency score multiplied by the severity score. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Placebo Ophthalmic Solution
n=23 Participants
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
0.017% P-321 Ophthalmic Solution
n=24 Participants
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score.
Change from Baseline (V2) to Day 15 (V3)
|
-4.759 units on a scale
Standard Deviation 16.0865
|
-2.985 units on a scale
Standard Deviation 16.2819
|
|
Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score.
Baseline
|
58.821 units on a scale
Standard Deviation 17.0381
|
59.228 units on a scale
Standard Deviation 17.7064
|
Adverse Events
0.017% P-321 Ophthalmic Solution
Placebo Ophthalmic Solution
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
0.017% P-321 Ophthalmic Solution
n=24 participants at risk
Subjects received 0.017% P-321 Ophthalmic Solution TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
Placebo Ophthalmic Solution
n=23 participants at risk
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
|
|---|---|---|
|
Eye disorders
Conjunctival disorders
|
4.2%
1/24 • Number of events 1 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
0.00%
0/23 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
|
Eye disorders
Eyelid Oedema
|
4.2%
1/24 • Number of events 2 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
0.00%
0/23 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
|
Eye disorders
Instillation Site Pain
|
0.00%
0/24 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
4.3%
1/23 • Number of events 1 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
|
Eye disorders
Fatigue
|
4.2%
1/24 • Number of events 1 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
0.00%
0/23 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
|
Eye disorders
Upper Respiratory Tract Infection
|
4.2%
1/24 • Number of events 1 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
0.00%
0/23 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
|
Eye disorders
Muscle Strain
|
0.00%
0/24 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
4.3%
1/23 • Number of events 1 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
|
Eye disorders
Dysgeusia
|
8.3%
2/24 • Number of events 2 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
0.00%
0/23 • 29 days
An AE was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE (TEAE) was an AE that either commenced following initiation of study treatment or was present prior to study treatment but increased in frequency or severity following initiation of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigator may publish or present the results based on data generated at their Institution, provided that: (a) Sponsor publishes the results from all sites participating in the Study; (b) Institution receives notification from Sponsor that publication of the multi-site results is no longer planned; or (c) eighteen (18) months following the close of study, whichever occurs first.
- Publication restrictions are in place
Restriction type: OTHER