Dry Eye Syndrome
Conditions
Brief summary
In subjects with Dry Eye Syndrome: The primary objective of this study is to compare the safety and tolerability of TOP1630 Ophthalmic Solution to placebo. The secondary objectives are to compare the efficacy of TOP1630 Ophthalmic Solution to placebo for the treatment of the signs and symptoms of dry eye syndrome.
Detailed description
This study is designed to assess the safety, tolerability and efficacy of TOP1630 ophthalmic solution in subjects with Dry Eye Syndrome. Eligible subjects will be randomized double masked to either TOP1630 or placebo. Part 1 (time frame 12 days) comprises assessment of safety, tolerability and ocular comfort. Part 2 (time frame 35 days) comprises assessment of safety, tolerability and efficacy
Interventions
DRUGTOP1630 Ophthalmic Solution
Bilateral ocular drug administration
DRUGPlacebo to TOP1630 Ophthalmic Solution
Bilateral ocular drug administration
Sponsors
Topivert Pharma Ltd
ORA, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be at least 18 years of age; * Provide written informed consent; * Have a reported history of dry eye; * Have a history of use of eye drops for dry eye symptoms; Additionally for Part 2 Symptoms of dry eye syndrome including: * Ocular discomfort * Conjunctival redness * Tear film break up time * Schirmer test score Signs of dry eye syndrome including: Conjunctival staining score
Exclusion criteria
* Have any clinically significant slit lamp findings at entry visit ; * Be diagnosed with an ongoing ocular infection; * Have any significant ocular lesion that could interfere with assessment of safety or efficacy or prevent study conduct in the opinion of the PI; * Have any planned ocular and/or lid surgeries over the study period; * Have an uncontrolled systemic disease; * Be a woman who is pregnant, nursing or planning a pregnancy; * Be a woman of childbearing potential who is not using an acceptable means of birth control; * Have a known allergy and/or sensitivity to the test article or its components; * Have a condition or be in a situation which the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vital Signs - Diastolic Blood Pressure | Part 1: 12 days time frame; Part 2: 35 days time frame | Changes in vital signs is performed to assess changes from baseline |
| Intraocular Pressure | Part 1: 12 days time frame; Part 2: 35 days time frame | a non-contact tonometer will be used to perform IOP to assess changes from baseline. |
| Corneal Sensitivity | Part 1: 12 days time frame; Part 2: 35 days time frame | The aesthesiometer will be used to perform corneal sensitivity to assess changes from baseline. Corneal Sensitivity Scale. Scale of 0-6 |
| Undilated Fundoscopy | Part 2: 35 days time frame | Non-Contact undilated fundoscopy exam will be performed to assess changes from baseline; outcome measure is number of patients with no abnormalities |
| Vital Signs - Pulse | Part 1: 12 days time frame; Part 2: 35 days time frame | Changes in vital signs is performed to assess changes from baseline |
| Vital Signs - O2 Saturation | Part 1: 12 days time frame; Part 2: 35 days time frame | Changes in vital signs is performed to assess changes from baseline |
| Vital Signs - Systolic Blood Pressure | Part 1: 12 days time frame; Part 2: 35 days time frame | Changes in vital signs is performed to assess changes from baseline |
| Visual Acuity | Part 1: 12 days time frame; Part 2: 35 days time frame | Visual Acuity will be measured using the EDTRS chart to assess changes from baseline |
| Slit-lamp Biomicroscopy | Part 1: 12 days time frame; Part 2: 35 days time frame | Slit lamp biomicroscopy exams will be performed to assess any changes from baseline; outcome measure is number of patients with no abnormalities |
| Drop Comfort Assessment | Part 1: 12 days time frame | The comfort of the eye drop will be performed to assess changes from baseline. Drop Comfort Assessment Scale; 0-10; 0 being very comfortable and 10 being very uncomfortable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dry Eye Symptoms | Part 2: 35 days time frame | Dry eye syndrome symptom assessment Scale (grittiness) (0-5 scale where 0 = none and 5 = worst) |
| Dry Eye Signs | Part 2: 35 days time frame | Dry eye syndrome staining Score assessments (total lissamine green staining score, 0-20 where 0 = no staining) |
| Tear Film Break up Time | Part 2: 35 days time frame | Tear film break up time measured (in seconds) after instillation of sodium fluorescein solution |
| Schirmer's Test | Part 2: 35 days time frame | Measurement of Schirmer test strips (mm length of moistened area after 5 minutes) |
| Daily Symptom Assessment | Assessed daily between visit 3b (day 27) to visit 4b (day 35) | Daily symptom assessment using diary cards - outcome for worst symptom, ie symptom with highest severity score at baseline for each patient; calculated using the daily average between visit 3b to visit 4b Ora Calibra Ocular Discomfort & 4-Symptom Questionnaire (0-5 scale where 0 = none and 5 = worst) |
| Ocular Discomfort | Part 2: 35 days time frame | Ocular discomfort Scale severity assessment (0-4 scale where 0 = none and 4 = constant) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active TOP1630 Ophthalmic Solution
TOP1630 Ophthalmic Solution: Bilateral ocular drug administration | 31 |
| Placebo Placebo (Vehicle) Ophthalmic Solution
Placebo to TOP1630 Ophthalmic Solution: Bilateral ocular drug administration | 30 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Active |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 28 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 33 Participants | 17 Participants |
| Age, Continuous | 65.3 years STANDARD_DEVIATION 11.92 | 63.9 years STANDARD_DEVIATION 11.67 | 62.5 years STANDARD_DEVIATION 11.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 59 Participants | 31 Participants |
| Region of Enrollment United States | 30 participants | 61 participants | 31 participants |
| Sex: Female, Male Female | 16 Participants | 36 Participants | 20 Participants |
| Sex: Female, Male Male | 14 Participants | 25 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 32 |
| other Total, other adverse events | 6 / 37 | 4 / 32 |
| serious Total, serious adverse events | 0 / 37 | 0 / 32 |
Outcome results
Primary
Corneal Sensitivity
The aesthesiometer will be used to perform corneal sensitivity to assess changes from baseline. Corneal Sensitivity Scale. Scale of 0-6
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
Population: Number analyzed comes from Part 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Corneal Sensitivity | 59.8 unit of measure mm | Standard Deviation 0.91 |
| Placebo | Corneal Sensitivity | 59.4 unit of measure mm | Standard Deviation 1.74 |
Primary
Drop Comfort Assessment
The comfort of the eye drop will be performed to assess changes from baseline. Drop Comfort Assessment Scale; 0-10; 0 being very comfortable and 10 being very uncomfortable
Time frame: Part 1: 12 days time frame
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Drop Comfort Assessment | 0.71 score on a scale | Standard Deviation 0.846 |
| Placebo | Drop Comfort Assessment | 1.38 score on a scale | Standard Deviation 0.495 |
Primary
Intraocular Pressure
a non-contact tonometer will be used to perform IOP to assess changes from baseline.
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
Population: Number analyzed comes from Part 1 and Part 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Intraocular Pressure | Part 1 | 12.3 unit of measure mmHg | Standard Deviation 1.03 |
| Active | Intraocular Pressure | Part 2 | 12.4 unit of measure mmHg | Standard Deviation 1.75 |
| Placebo | Intraocular Pressure | Part 1 | 15.5 unit of measure mmHg | Standard Deviation 0.71 |
| Placebo | Intraocular Pressure | Part 2 | 12.8 unit of measure mmHg | Standard Deviation 2.54 |
Primary
Slit-lamp Biomicroscopy
Slit lamp biomicroscopy exams will be performed to assess any changes from baseline; outcome measure is number of patients with no abnormalities
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active | Slit-lamp Biomicroscopy | Part 1 | 6 participants |
| Active | Slit-lamp Biomicroscopy | Part 2 | 31 participants |
| Placebo | Slit-lamp Biomicroscopy | Part 1 | 2 participants |
| Placebo | Slit-lamp Biomicroscopy | Part 2 | 30 participants |
Primary
Undilated Fundoscopy
Non-Contact undilated fundoscopy exam will be performed to assess changes from baseline; outcome measure is number of patients with no abnormalities
Time frame: Part 2: 35 days time frame
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Undilated Fundoscopy | 31 Participants |
| Placebo | Undilated Fundoscopy | 30 Participants |
Primary
Visual Acuity
Visual Acuity will be measured using the EDTRS chart to assess changes from baseline
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
Population: Number analyzed represents the sum of numbers analyzed Part 1 and Part 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Visual Acuity | Part 1 | 0.05 logMAR | Standard Deviation 0.143 |
| Active | Visual Acuity | Part 2 | 0.017 logMAR | Standard Deviation 0.1163 |
| Placebo | Visual Acuity | Part 2 | 0.075 logMAR | Standard Deviation 0.1242 |
| Placebo | Visual Acuity | Part 1 | -0.09 logMAR | Standard Deviation 0.156 |
Primary
Vital Signs - Diastolic Blood Pressure
Changes in vital signs is performed to assess changes from baseline
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
Population: Number analyzed comes from Part 1 and Part 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Vital Signs - Diastolic Blood Pressure | Part 2 | 71.2 mmHg | Standard Deviation 9.53 |
| Active | Vital Signs - Diastolic Blood Pressure | Part 1 | 72.7 mmHg | Standard Deviation 8.69 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Part 2 | 72.0 mmHg | Standard Deviation 9.39 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Part 1 | 89.5 mmHg | Standard Deviation 9.19 |
Primary
Vital Signs - O2 Saturation
Changes in vital signs is performed to assess changes from baseline
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
Population: Number analyzed comes from Part 1 and Part 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Vital Signs - O2 Saturation | Part 1 | 95.8 percentage of 02 saturation | Standard Deviation 1.94 |
| Active | Vital Signs - O2 Saturation | Part 2 | 96.3 percentage of 02 saturation | Standard Deviation 1.75 |
| Placebo | Vital Signs - O2 Saturation | Part 1 | 97.0 percentage of 02 saturation | Standard Deviation 1.41 |
| Placebo | Vital Signs - O2 Saturation | Part 2 | 95.7 percentage of 02 saturation | Standard Deviation 1.66 |
Primary
Vital Signs - Pulse
Changes in vital signs is performed to assess changes from baseline
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
Population: Number analyzed comes from Part 1 and Part 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Vital Signs - Pulse | Part 1 | 64.3 beats per minute | Standard Deviation 9.09 |
| Active | Vital Signs - Pulse | Part 2 | 68.8 beats per minute | Standard Deviation 10.55 |
| Placebo | Vital Signs - Pulse | Part 1 | 75.0 beats per minute | Standard Deviation 4.24 |
| Placebo | Vital Signs - Pulse | Part 2 | 70.5 beats per minute | Standard Deviation 15.66 |
Primary
Vital Signs - Systolic Blood Pressure
Changes in vital signs is performed to assess changes from baseline
Time frame: Part 1: 12 days time frame; Part 2: 35 days time frame
Population: Number analyzed comes from Part 1 and Part 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Vital Signs - Systolic Blood Pressure | Part 1 | 128.0 mmHg | Standard Deviation 29.32 |
| Active | Vital Signs - Systolic Blood Pressure | Part 2 | 120.9 mmHg | Standard Deviation 15.97 |
| Placebo | Vital Signs - Systolic Blood Pressure | Part 1 | 148.5 mmHg | Standard Deviation 3.54 |
| Placebo | Vital Signs - Systolic Blood Pressure | Part 2 | 128.2 mmHg | Standard Deviation 17.1 |
Secondary
Daily Symptom Assessment
Daily symptom assessment using diary cards - outcome for worst symptom, ie symptom with highest severity score at baseline for each patient; calculated using the daily average between visit 3b to visit 4b Ora Calibra Ocular Discomfort & 4-Symptom Questionnaire (0-5 scale where 0 = none and 5 = worst)
Time frame: Assessed daily between visit 3b (day 27) to visit 4b (day 35)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Daily Symptom Assessment | 2.33 score on a scale | Standard Deviation 0.832 |
| Placebo | Daily Symptom Assessment | 2.69 score on a scale | Standard Deviation 0.648 |
Comparison: Change from baseline. ANCOVA model includes baseline score as a covariate.p-value: 0.0690% CI: [-0.48, 0.03]ANCOVA
Secondary
Dry Eye Signs
Dry eye syndrome staining Score assessments (total lissamine green staining score, 0-20 where 0 = no staining)
Time frame: Part 2: 35 days time frame
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Dry Eye Signs | 5.88 score on a scale | Standard Deviation 2.37 |
| Placebo | Dry Eye Signs | 6.60 score on a scale | Standard Deviation 2.55 |
Comparison: Change from baseline. ANCOVA model includes baseline score as a covariate.p-value: 0.0390% CI: [-2.36, -0.47]ANCOVA
Secondary
Dry Eye Symptoms
Dry eye syndrome symptom assessment Scale (grittiness) (0-5 scale where 0 = none and 5 = worst)
Time frame: Part 2: 35 days time frame
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Dry Eye Symptoms | 1.7 score on a scale | Standard Deviation 1.42 |
| Placebo | Dry Eye Symptoms | 2.8 score on a scale | Standard Deviation 1.38 |
Comparison: Change form baseline. ANCOVA model includes baseline score as a covariate.p-value: 0.000190% CI: [-1.4, 0.5]ANCOVA
Secondary
Ocular Discomfort
Ocular discomfort Scale severity assessment (0-4 scale where 0 = none and 4 = constant)
Time frame: Part 2: 35 days time frame
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Ocular Discomfort | 3.5 score on a scale | Standard Deviation 0.78 |
| Placebo | Ocular Discomfort | 3.9 score on a scale | Standard Deviation 0.31 |
Comparison: Change from Baseline. ANCOVA model includes baseline scores as a covariatep-value: 0.0290% CI: [-0.7, 0]ANCOVA
Secondary
Schirmer's Test
Measurement of Schirmer test strips (mm length of moistened area after 5 minutes)
Time frame: Part 2: 35 days time frame
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Schirmer's Test | 6.2 mm in 5 minutes | Standard Deviation 4.19 |
| Placebo | Schirmer's Test | 6.7 mm in 5 minutes | Standard Deviation 4.94 |
Comparison: Change from baseline. ANCOVA model includes baseline score as a covariate.p-value: 0.9790% CI: [-1.7, 2]ANCOVA
Secondary
Tear Film Break up Time
Tear film break up time measured (in seconds) after instillation of sodium fluorescein solution
Time frame: Part 2: 35 days time frame
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Tear Film Break up Time | 1.629 Seconds | Standard Deviation 0.85 |
| Placebo | Tear Film Break up Time | 1.480 Seconds | Standard Deviation 0.39 |
Comparison: Change from Baseline; ANCOVA model includes baseline score as a covariate.p-value: 0.3990% CI: [-0.177, 0.575]ANCOVA