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

• Sponsor: Parion Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02831387
• Collaborator: (none)
• Enrollment: 47
• Locations: 7
• Arms: 2
• Duration (Months): 11
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of treatment with 0.017% P-321 on Dry Eye Symptoms.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Disease	Drug: P-321 Ophthalmic Solution; Drug: P-321 Ophthalmic Solution placebo	Phase 2

Detailed Description

This is a multi-center, randomized, double-masked, placebo-controlled, parallel group Phase 2b trial designed to evaluate symptoms and signs in subjects with mild to moderate dry eye disease. Eligible patients, will be treated with placebo during 2-week placebo run-in period. Subjects will then be randomly assigned in a double-masked, 1:1 ratio to either 0.017% P-321 Ophthalmic Solution or placebo TID for 28 days. This study is designed to evaluate the changes in symptoms. Safety will be assessed throughout the study by adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Masked, Parallel Group Study of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease Assessing Safety and Efficacy Over 28 Days
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.017% P-321 Ophthalmic Solution 0.017% P-321 Ophthalmic Solution TID for 28 days.	Drug: P-321 Ophthalmic Solution; P-321 Ophthalmic Solution 0.017%; Other Names: P-321
Placebo Comparator: Placebo P-321 Ophthalmic Solution Placebo TID for 28 days.	Drug: P-321 Ophthalmic Solution placebo; Placebo to match P-321 Ophthalmic Solution; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline (Visit 2) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire. [Baseline to Day 29]

   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.

Secondary Outcome Measures

1. Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores [Baseline to Day 29]

   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.

2. Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores [Baseline to Day 29]

   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.

3. Change From Baseline to Day 29 in Fluorescein Staining of the Cornea. [Baseline to Day 29]

   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.

4. Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva. [Baseline to Day 29]

   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.

5. Number of Participants With at Least 20% Improvement in Symptoms From Baseline to Day 29 [Baseline to Day 29]

   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.

6. Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score. [Baseline to Day 15]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Provide written informed consent

2. Male or female subjects aged 18 to 80 years, inclusive

3. Have a history of dry eye disease (DED) in both eyes

4. Be on stable regimens of other needed medications

5. Have a BCVA of +0.7 or better as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS)

6. Have reported symptoms

7. Have the following signs in at least one eye: Schirmer score without anesthesia of >1 and <10 mm at 5 minutes and staining of conjunctival and corneal areas of the eye.

8. Have normal lid anatomy

Exclusion Criteria:

1. Have undergone refractive eye surgery in the past 12 months

2. Have undergone previous eyelid surgery in either eye (External blepharoplasty not resulting in exposure or abnormal blinking is allowed)

3. Have lid irregularities or deformities

4. Have a history of glaucoma, a history of an elevated lOP within the past year, or an lOP in either eye > 25 mmHg at the Screening Visit (Visit 1)

5. Have any clinically significant, uncontrolled, or unstable medical or surgical conditions that could affect his or her ability to participate

6. Have permanent punctal plugs, punctal occlusion, or history of nasolacrimal duct obstruction. Removable punctal plugs are allowed if they have been used regularly for at least 60 days prior to the screening visit. However, if a plug comes out during the study it must be promptly replaced.

7. Have clinical findings of severe Meibomian Gland Dysfunction (MGD) in the Study Eye

8. Are pregnant or breast feeding

9. Use of any investigational product or device within 28 days prior to the Screening Visit or during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sall Research Medical Center	Artesia	California	United States	90701
2	Tauber Eye Center	Kansas City	Missouri	United States	64111
3	Ophthalmology Associates	Saint Louis	Missouri	United States	63131
4	Comprehensive Eye Care, Ltd.	Washington	Missouri	United States	63090
5	UNC Kittner Eye Center	Chapel Hill	North Carolina	United States	27517
6	Ocular Surface Center, Baylor College of Medicine	Houston	Texas	United States	77030
7	Virginia Eye Consultants	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Parion Sciences

Investigators

• Study Director: Jose Boyer, Parion Sciences

Study Documents (Full-Text)

• Study Protocol - Feb 10, 2017
• Statistical Analysis Plan - Aug 8, 2017

More Information

Publications

None provided.

• Responsible Party: Parion Sciences
• ClinicalTrials.gov Identifier: NCT02831387
• Other Study ID Numbers: P-321-202
• First Posted: Jul 13, 2016
• Last Update Posted: Oct 11, 2018
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	Placebo Ophthalmic Solution	0.017% P-321 Ophthalmic Solution
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

Baseline Characteristics

Arm/Group Title	Placebo Ophthalmic Solution	0.017% P-321 Ophthalmic Solution	Total
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 Participants	23	24	47
Age (Count of Participants)
<=18 years	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 (Count of Participants)
Female	18 78.3%	20 83.3%	38 80.9%
Male	5 21.7%	4 16.7%	9 19.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 26.1%	6 25%	12 25.5%
Not Hispanic or Latino	17 73.9%	18 75%	35 74.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%	24 100%	47 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (Visit 2) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire.
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

Outcome Measure Data

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
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)
Measure Participants	23	24
Baseline	58.821 (17.0381)	59.228 (17.7064)
Change from Baseline (Visit 2) to Day 29	-9.197 (24.4776)	-9.989 (12.2523)

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
Statistical Test of Hypothesis	p-Value	0.749
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.88
	Confidence Interval	(2-Sided) 95%; -13.696 to 9.936
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores
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

Outcome Measure Data

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
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)
Measure Participants	23	24
Baseline	57.2 (19.58)	62.3 (17.91)
Change from Baseline (Visit 2) to Day 29	-5.3 (25.45)	-12.3 (14.13)

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
Statistical Test of Hypothesis	p-Value	0.267
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.6
	Confidence Interval	(2-Sided) 95%; -18.4 to 5.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores
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

Outcome Measure Data

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
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)
Measure Participants	23	24
Baseline	61.1 (15.54)	56.5 (18.45)
Change from Baseline (Visit 2) to Day 29	-13.2 (24.70)	-7.6 (12.88)

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
Statistical Test of Hypothesis	p-Value	0.495
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -7.6 to 15.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Day 29 in Fluorescein Staining of the Cornea.
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

Outcome Measure Data

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
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)
Measure Participants	23	24
Baseline	5.8 (1.31)	6.3 (1.58)
Change from Baseline (Visit 2) to Day 29	-1.2 (2.4)	-0.7 (2.68)

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
Statistical Test of Hypothesis	p-Value	0.316
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva.
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

Outcome Measure Data

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
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)
Measure Participants	23	24
Baseline	7.6 (1.73)	7.1 (1.79)
Change from Baseline (Visit 2) to Day 29	-0.3 (3.41)	-0.2 (3.78)

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
Statistical Test of Hypothesis	p-Value	0.823
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.9 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Participants With at Least 20% Improvement in Symptoms From Baseline to Day 29
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

Outcome Measure Data

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
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)
Measure Participants	22	22
Count of Participants [Participants]	8 34.8%	11 45.8%

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.923
	Confidence Interval	(2-Sided) 95%; 0.515 to 7.184
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score.
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

Outcome Measure Data

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
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)
Measure Participants	23	24
Baseline	58.821 (17.0381)	59.228 (17.7064)
Change from Baseline (V2) to Day 15 (V3)	-4.759 (16.0865)	-2.985 (16.2819)

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
Statistical Test of Hypothesis	p-Value	0.723
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.666
	Confidence Interval	(2-Sided) 95%; -7.759 to 11.092
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)
Serious Adverse Events
	0.017% P-321 Ophthalmic Solution		Placebo Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	0.017% P-321 Ophthalmic Solution		Placebo Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/24 (16.7%)		2/23 (8.7%)
Eye disorders
Conjunctival disorders	1/24 (4.2%)	1	0/23 (0%)	0
Eyelid Oedema	1/24 (4.2%)	2	0/23 (0%)	0
Instillation Site Pain	0/24 (0%)	0	1/23 (4.3%)	1
Fatigue	1/24 (4.2%)	1	0/23 (0%)	0
Upper Respiratory Tract Infection	1/24 (4.2%)	1	0/23 (0%)	0
Muscle Strain	0/24 (0%)	0	1/23 (4.3%)	1
Dysgeusia	2/24 (8.3%)	2	0/23 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.