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Evaluation of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease

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ClinicalTrials.gov Identifier: NCT02831387
Recruitment Status : Terminated
First Posted : July 13, 2016
Results First Posted : October 11, 2018
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Parion Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Dry Eye Disease
Interventions Drug: P-321 Ophthalmic Solution
Drug: P-321 Ophthalmic Solution placebo
Enrollment 47
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29) 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)
Period Title: Overall Study
Started 23 24
Completed 22 22
Not Completed 1 2
Reason Not Completed
Withdrawal by Subject             1             1
Discontinued due to stock recovery             0             1
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution Total
Hide Arm/Group Description Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29) 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 of all reporting groups
Overall Number of Baseline Participants 23 24 47
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 24 participants 47 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
17
  73.9%
17
  70.8%
34
  72.3%
>=65 years
6
  26.1%
7
  29.2%
13
  27.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 24 participants 47 participants
Female
18
  78.3%
20
  83.3%
38
  80.9%
Male
5
  21.7%
4
  16.7%
9
  19.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 24 participants 47 participants
Hispanic or Latino
6
  26.1%
6
  25.0%
12
  25.5%
Not Hispanic or Latino
17
  73.9%
18
  75.0%
35
  74.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 23 participants 24 participants 47 participants
23 24 47
1.Primary Outcome
Title Change From Baseline (Visit 2) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire.
Hide Description 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.
Time Frame Baseline to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description:
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
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 Number of Participants Analyzed 23 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 22 participants 23 participants
58.821  (17.0381) 59.228  (17.7064)
Change from Baseline (Visit 2) to Day 29 Number Analyzed 22 participants 22 participants
-9.197  (24.4776) -9.989  (12.2523)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Ophthalmic Solution, 0.017% P-321 Ophthalmic Solution
Comments Statistical Analysis 1 for Change From Baseline to Day 29 in the Subject Reported Dry Eye Questionnaire
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.749
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.88
Confidence Interval (2-Sided) 95%
-13.696 to 9.936
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores
Hide Description 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.
Time Frame Baseline to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description:
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
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 Number of Participants Analyzed 23 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 22 participants 23 participants
57.2  (19.58) 62.3  (17.91)
Change from Baseline (Visit 2) to Day 29 Number Analyzed 22 participants 22 participants
-5.3  (25.45) -12.3  (14.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Ophthalmic Solution, 0.017% P-321 Ophthalmic Solution
Comments Statistical Analysis 1 for Change From Baseline (Visit 2) to Day 29 in Frequency Scores
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.267
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.6
Confidence Interval (2-Sided) 95%
-18.4 to 5.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores
Hide Description 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.
Time Frame Baseline to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description:
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
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 Number of Participants Analyzed 23 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 22 participants 23 participants
61.1  (15.54) 56.5  (18.45)
Change from Baseline (Visit 2) to Day 29 Number Analyzed 22 participants 22 participants
-13.2  (24.70) -7.6  (12.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Ophthalmic Solution, 0.017% P-321 Ophthalmic Solution
Comments Statistical Analysis 1 for Change From Baseline (Visit 2) to Day 29 in Severity Scores
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.495
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
-7.6 to 15.4
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Day 29 in Fluorescein Staining of the Cornea.
Hide Description 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.
Time Frame Baseline to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description:
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
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 Number of Participants Analyzed 23 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 22 participants 23 participants
5.8  (1.31) 6.3  (1.58)
Change from Baseline (Visit 2) to Day 29 Number Analyzed 22 participants 22 participants
-1.2  (2.4) -0.7  (2.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Ophthalmic Solution, 0.017% P-321 Ophthalmic Solution
Comments Statistical Analysis 1 for Change From Baseline to Day 29 in Fluorescein Staining of the Cornea
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.316
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.6 to 1.9
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva.
Hide Description 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.
Time Frame Baseline to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description:
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
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 Number of Participants Analyzed 23 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 22 participants 23 participants
7.6  (1.73) 7.1  (1.79)
Change from Baseline (Visit 2) to Day 29 Number Analyzed 22 participants 22 participants
-0.3  (3.41) -0.2  (3.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Ophthalmic Solution, 0.017% P-321 Ophthalmic Solution
Comments Statistical Analysis 1 for Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.823
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.9 to 1.5
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With at Least 20% Improvement in Symptoms From Baseline to Day 29
Hide Description 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.
Time Frame Baseline to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description:
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
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 Number of Participants Analyzed 22 22
Measure Type: Count of Participants
Unit of Measure: Participants
8
  36.4%
11
  50.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Ophthalmic Solution, 0.017% P-321 Ophthalmic Solution
Comments Statistical Analysis 1 for the Number of participants with at least 20% improvement in symptoms from baseline to Day 29
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.923
Confidence Interval (2-Sided) 95%
0.515 to 7.184
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score.
Hide Description 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.
Time Frame Baseline to Day 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Ophthalmic Solution 0.017% P-321 Ophthalmic Solution
Hide Arm/Group Description:
Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
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 Number of Participants Analyzed 23 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 22 participants 23 participants
58.821  (17.0381) 59.228  (17.7064)
Change from Baseline (V2) to Day 15 (V3) Number Analyzed 22 participants 23 participants
-4.759  (16.0865) -2.985  (16.2819)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Ophthalmic Solution, 0.017% P-321 Ophthalmic Solution
Comments Statistical Analysis 1 for Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.723
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.666
Confidence Interval (2-Sided) 95%
-7.759 to 11.092
Estimation Comments [Not Specified]
Time Frame 29 days
Adverse Event Reporting Description 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.
 
Arm/Group Title 0.017% P-321 Ophthalmic Solution Placebo Ophthalmic Solution
Hide Arm/Group Description 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) Subject received Placebo TID administration in both eyes from Visit 2 (Randomization - Treatment Day 1) through the day before Visit 4 (Treatment Day 29)
All-Cause Mortality
0.017% P-321 Ophthalmic Solution Placebo Ophthalmic Solution
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)      0/23 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
0.017% P-321 Ophthalmic Solution Placebo Ophthalmic Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      0/23 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
0.017% P-321 Ophthalmic Solution Placebo Ophthalmic Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/24 (16.67%)      2/23 (8.70%)    
Eye disorders     
Conjunctival disorders * 1  1/24 (4.17%)  1 0/23 (0.00%)  0
Eyelid Oedema * 1  1/24 (4.17%)  2 0/23 (0.00%)  0
Instillation Site Pain * 1  0/24 (0.00%)  0 1/23 (4.35%)  1
Fatigue * 1  1/24 (4.17%)  1 0/23 (0.00%)  0
Upper Respiratory Tract Infection * 1  1/24 (4.17%)  1 0/23 (0.00%)  0
Muscle Strain * 1  0/24 (0.00%)  0 1/23 (4.35%)  1
Dysgeusia * 1  2/24 (8.33%)  2 0/23 (0.00%)  0
1
Term from vocabulary, Not specified
*
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.
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.
Results Point of Contact
Name/Title: Jose Boyer
Organization: Parion Sciences
Phone: 919-313-1182
Responsible Party: Parion Sciences
ClinicalTrials.gov Identifier: NCT02831387     History of Changes
Other Study ID Numbers: P-321-202
First Submitted: July 1, 2016
First Posted: July 13, 2016
Results First Submitted: June 29, 2018
Results First Posted: October 11, 2018
Last Update Posted: October 11, 2018