Dry Eye Disease
Conditions
Brief summary
The purpose of this study is to evaluate the effect of treatment with 0.017% P-321 on Dry Eye Symptoms.
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.
Interventions
P-321 Ophthalmic Solution 0.017%
Placebo to match P-321 Ophthalmic Solution
Sponsors
Parion Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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) | 23 |
| 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) | 24 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued due to stock recovery | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Ophthalmic Solution | 0.017% P-321 Ophthalmic Solution | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 17 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 18 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 23 participants | 24 participants | 47 participants |
| Sex: Female, Male Female | 18 Participants | 20 Participants | 38 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 4 / 24 | 2 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 |
Outcome results
Primary
Change From Baseline (Visit 2) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Ophthalmic Solution | 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 |
| Placebo Ophthalmic Solution | 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 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline (Visit 2) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire. | Baseline | 59.228 units on a scale | Standard Deviation 17.7064 |
| 0.017% P-321 Ophthalmic Solution | 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 | -9.989 units on a scale | Standard Deviation 12.2523 |
Comparison: Statistical Analysis 1 for Change From Baseline to Day 29 in the Subject Reported Dry Eye Questionnairep-value: 0.74995% CI: [-13.696, 9.936]Mixed Models Analysis
Secondary
Change From Baseline to Day 29 in Fluorescein Staining of the Cornea.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Ophthalmic Solution | Change From Baseline to Day 29 in Fluorescein Staining of the Cornea. | Baseline | 5.8 units on a scale | Standard Deviation 1.31 |
| Placebo Ophthalmic Solution | 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 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline to Day 29 in Fluorescein Staining of the Cornea. | Baseline | 6.3 units on a scale | Standard Deviation 1.58 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline to Day 29 in Fluorescein Staining of the Cornea. | Change from Baseline (Visit 2) to Day 29 | -0.7 units on a scale | Standard Deviation 2.68 |
Comparison: Statistical Analysis 1 for Change From Baseline to Day 29 in Fluorescein Staining of the Corneap-value: 0.31695% CI: [-0.6, 1.9]Mixed Models Analysis
Secondary
Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Ophthalmic Solution | Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva. | Baseline | 7.6 units on a scale | Standard Deviation 1.73 |
| Placebo Ophthalmic Solution | 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 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva. | Baseline | 7.1 units on a scale | Standard Deviation 1.79 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva. | Change from Baseline (Visit 2) to Day 29 | -0.2 units on a scale | Standard Deviation 3.78 |
Comparison: Statistical Analysis 1 for Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctivap-value: 0.82395% CI: [-1.9, 1.5]Mixed Models Analysis
Secondary
Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Ophthalmic Solution | 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 |
| Placebo Ophthalmic Solution | 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 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score. | Baseline | 59.228 units on a scale | Standard Deviation 17.7064 |
| 0.017% P-321 Ophthalmic Solution | 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) | -2.985 units on a scale | Standard Deviation 16.2819 |
Comparison: Statistical Analysis 1 for Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Scorep-value: 0.72395% CI: [-7.759, 11.092]Mixed Models Analysis
Secondary
Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Ophthalmic Solution | Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores | Baseline | 57.2 units on a scale | Standard Deviation 19.58 |
| Placebo Ophthalmic Solution | 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 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores | Baseline | 62.3 units on a scale | Standard Deviation 17.91 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores | Change from Baseline (Visit 2) to Day 29 | -12.3 units on a scale | Standard Deviation 14.13 |
Comparison: Statistical Analysis 1 for Change From Baseline (Visit 2) to Day 29 in Frequency Scoresp-value: 0.26795% CI: [-18.4, 5.3]Mixed Models Analysis
Secondary
Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Ophthalmic Solution | Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores | Baseline | 61.1 units on a scale | Standard Deviation 15.54 |
| Placebo Ophthalmic Solution | 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 24.7 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores | Baseline | 56.5 units on a scale | Standard Deviation 18.45 |
| 0.017% P-321 Ophthalmic Solution | Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores | Change from Baseline (Visit 2) to Day 29 | -7.6 units on a scale | Standard Deviation 12.88 |
Comparison: Statistical Analysis 1 for Change From Baseline (Visit 2) to Day 29 in Severity Scoresp-value: 0.49595% CI: [-7.6, 15.4]Mixed Models Analysis
Secondary
Number of Participants With at Least 20% Improvement in Symptoms From 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.
Time frame: Baseline to Day 29
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Ophthalmic Solution | Number of Participants With at Least 20% Improvement in Symptoms From Baseline to Day 29 | 8 Participants |
| 0.017% P-321 Ophthalmic Solution | Number of Participants With at Least 20% Improvement in Symptoms From Baseline to Day 29 | 11 Participants |
Comparison: Statistical Analysis 1 for the Number of participants with at least 20% improvement in symptoms from baseline to Day 2995% CI: [0.515, 7.184]