Dry Eye Syndrome
Conditions
Keywords
Dry eyes, Ocular discomfort
Brief summary
The purpose of this study was to determine if Sodium Hyaluronate, 0.18% is effective in treating the signs and symptoms of dry eye disease.
Interventions
DRUGSodium Hyaluronate Ophthalmic Solution, 0.18%
OTHERVehicle
Inactive ingredients used as run-in and placebo comparator
Sponsors
Alcon Research
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
* Documented history of dry eyes for at least 3 months. * Ocular discomfort due to dry eyes. * Presence of corneal and conjunctival staining. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Women who are pregnant or lactating. * Contact lens wear within 1 week before Screening and during the study. * Ocular surgery (of any type, including laser surgery) or ocular trauma within the 4 months prior to Screening. * Punctal plugs or punctal occlusion initiated within 3 months of screening * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lissamine Green Staining (LGS) Total Score at Day 7 | Baseline, Day 7 | The investigator instilled an ophthalmic dye on the eye and rated staining in three areas (cornea, nasal, and temporal conjunctiva). Staining was rated on a 5-point scale from 0 to 4 (0=0% to 4=\>45%). The LGS Total Score (0-12) is the sum of the three individual ratings. A more negative change indicates a greater amount of improvement. |
| Change From Baseline in Global Symptom Frequency (GSF) Total Score at Day 7 | Baseline, Day 7 | The subject completed a questionnaire and rated the frequency of five common dry eye symptoms. Frequency was rated on a 4-point scale from 0 to 3 (0=never to 3=constantly). The GSF Total Score (0-15) is the sum of the five individual ratings. A more negative change indicates a greater amount of improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in LGS Total Score at Day 14 | Baseline, Day 14 | The investigator instilled an ophthalmic dye on the eye and rated staining in three areas (cornea, nasal, and temporal conjunctiva). Staining was rated on a 5-point scale from 0 to 4 (0=0% to 4=\>45%). The LGS Total Score (0-12) is the sum of the three individual ratings. A more negative change indicates a greater amount of improvement. |
| Change From Baseline in GSF Total Score at Day 14 | Baseline, Day 14 | The subject completed a questionnaire and rated the frequency of five common dry eye symptoms. Frequency was rated on a 4-point scale from 0 to 3 (0=never to 3=constantly). The GSF Total Score (0-15) is the sum of the five individual ratings. A more negative change indicates a greater amount of improvement. |
| Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score | Baseline, up to Day 14 | The investigator instilled an ophthalmic dye on the eye and rated corneal staining by type, extent/surface area, and depth. Each staining was rated on a 5-point scale from 0 to 4 (0=no staining/0% to 4=patch/\>45%/immediate diffuse stromal glow). The CFS Total Score (0-12) is the sum of the three individual ratings. A more negative percentage change indicates a greater amount of improvement. |
| Percentage Change From Baseline in Schirmer I Score | Baseline, up to Day 14 | The investigator placed a paper strip on the eye under the lower lid and left it in place for 5 minutes. The Schirmer I Score was the length of the strip wetted by the tears (0-35 millimeters). A more positive percentage change indicates a greater amount of improvement. |
| Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score | Baseline, up to Day 14 | The subject completed a questionnaire and rated the intensity of five common dry eye symptoms. Intensity was rated on a visual analog scale from 0-100 (0=no symptoms to 100=severe symptoms). The GSI Total Score (0 to 500) is the sum of the five individual ratings. A more negative percentage change indicates a greater amount of improvement. |
| Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score | Baseline, up to Day 14 | For each of 5 common dry eye symptoms, the frequency (0-3) and intensity (0-100) scores were multiplied to obtain the symptom score (0-300). The 5 symptom scores were summed to obtain the Global Symptom Composite Index Score (0-1500). A more negative percentage change indicates a greater amount of improvement. |
| Proportion of Improved Scores on the Global Impact on Dry Eye Syndrome on Daily Life (GIDL) Rating | Baseline, Up to Day 14 | The subject was asked on a questionnaire, Please consider how your dry eyes feel when doing daily activities such as working on the computer, watching television, reading, and driving. Based on this, please rate the impact of your dry eye symptoms on your daily life, and responded on a 4-point scale from 0-3 (0=Absent to 3=Severe). Improved was defined as a change in score of \<0 from baseline. Proportion is reported as a percentage of participants. A greater percentage of subjects reporting a lower score indicates an improvement. |
Participant flow
Recruitment details
Subjects were recruited from 56 investigative sites in the United States.
Pre-assignment details
Of the 1936 subjects enrolled, 268 did not qualify for vehicle run-in and were exited as screen failures. Of the 1668 subjects receiving vehicle run-in, 214 did not qualify for randomization and were exited as screen failures. This reporting group includes the 1454 subjects randomized to receive treatment at Baseline Visit (Day 0).
Participants by arm
| Arm | Count |
|---|---|
| Sodium Hyaluronate Run-in, followed by Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days | 723 |
| Vehicle Run-in, followed by Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days | 727 |
| Total | 1,450 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Other | 4 | 2 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Subject Withdrew Consent | 5 | 2 |
Baseline characteristics
| Characteristic | Sodium Hyaluronate | Vehicle | Total |
|---|---|---|---|
| Age, Customized 18-64 years | 402 participants | 392 participants | 794 participants |
| Age, Customized ≥65 years | 321 participants | 335 participants | 656 participants |
| Region of Enrollment United States | 723 participants | 727 participants | 1450 participants |
| Sex: Female, Male Female | 590 Participants | 594 Participants | 1184 Participants |
| Sex: Female, Male Male | 133 Participants | 133 Participants | 266 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 723 | 0 / 727 |
| serious Total, serious adverse events | 1 / 723 | 1 / 727 |
Outcome results
Primary
Change From Baseline in Global Symptom Frequency (GSF) Total Score at Day 7
The subject completed a questionnaire and rated the frequency of five common dry eye symptoms. Frequency was rated on a 4-point scale from 0 to 3 (0=never to 3=constantly). The GSF Total Score (0-15) is the sum of the five individual ratings. A more negative change indicates a greater amount of improvement.
Time frame: Baseline, Day 7
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Change From Baseline in Global Symptom Frequency (GSF) Total Score at Day 7 | Baseline | 8.9 Units on a scale | Standard Deviation 2.3 |
| Sodium Hyaluronate | Change From Baseline in Global Symptom Frequency (GSF) Total Score at Day 7 | Change from Baseline at Day 7 | -1.6 Units on a scale | Standard Deviation 2.6 |
| Vehicle | Change From Baseline in Global Symptom Frequency (GSF) Total Score at Day 7 | Baseline | 9.1 Units on a scale | Standard Deviation 2.3 |
| Vehicle | Change From Baseline in Global Symptom Frequency (GSF) Total Score at Day 7 | Change from Baseline at Day 7 | -1.3 Units on a scale | Standard Deviation 2.4 |
Primary
Change From Baseline in Lissamine Green Staining (LGS) Total Score at Day 7
The investigator instilled an ophthalmic dye on the eye and rated staining in three areas (cornea, nasal, and temporal conjunctiva). Staining was rated on a 5-point scale from 0 to 4 (0=0% to 4=\>45%). The LGS Total Score (0-12) is the sum of the three individual ratings. A more negative change indicates a greater amount of improvement.
Time frame: Baseline, Day 7
Population: Modified Intent-to-Treat (mITT): The set of all randomized subjects who received at least one administration of the allocated product, had baseline efficacy measurement, had at least 1 post-baseline measurement and received the correct formulation of the lissamine green solution.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Change From Baseline in Lissamine Green Staining (LGS) Total Score at Day 7 | Baseline | 4.9 Units on a scale | Standard Deviation 2.2 |
| Sodium Hyaluronate | Change From Baseline in Lissamine Green Staining (LGS) Total Score at Day 7 | Change from Baseline at Day 7 | -0.8 Units on a scale | Standard Deviation 1.8 |
| Vehicle | Change From Baseline in Lissamine Green Staining (LGS) Total Score at Day 7 | Baseline | 4.8 Units on a scale | Standard Deviation 2.1 |
| Vehicle | Change From Baseline in Lissamine Green Staining (LGS) Total Score at Day 7 | Change from Baseline at Day 7 | -0.7 Units on a scale | Standard Deviation 1.6 |
Secondary
Change From Baseline in GSF Total Score at Day 14
The subject completed a questionnaire and rated the frequency of five common dry eye symptoms. Frequency was rated on a 4-point scale from 0 to 3 (0=never to 3=constantly). The GSF Total Score (0-15) is the sum of the five individual ratings. A more negative change indicates a greater amount of improvement.
Time frame: Baseline, Day 14
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Change From Baseline in GSF Total Score at Day 14 | Baseline | 8.9 Units on a scale | Standard Deviation 2.3 |
| Sodium Hyaluronate | Change From Baseline in GSF Total Score at Day 14 | Change from Baseline at Day 14 | -2.3 Units on a scale | Standard Deviation 2.8 |
| Vehicle | Change From Baseline in GSF Total Score at Day 14 | Baseline | 9.1 Units on a scale | Standard Deviation 2.3 |
| Vehicle | Change From Baseline in GSF Total Score at Day 14 | Change from Baseline at Day 14 | -2.2 Units on a scale | Standard Deviation 2.8 |
Secondary
Change From Baseline in LGS Total Score at Day 14
The investigator instilled an ophthalmic dye on the eye and rated staining in three areas (cornea, nasal, and temporal conjunctiva). Staining was rated on a 5-point scale from 0 to 4 (0=0% to 4=\>45%). The LGS Total Score (0-12) is the sum of the three individual ratings. A more negative change indicates a greater amount of improvement.
Time frame: Baseline, Day 14
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Change From Baseline in LGS Total Score at Day 14 | Baseline | 4.9 Units on a scale | Standard Deviation 2.2 |
| Sodium Hyaluronate | Change From Baseline in LGS Total Score at Day 14 | Change from Baseline at Day 14 | -1.2 Units on a scale | Standard Deviation 2 |
| Vehicle | Change From Baseline in LGS Total Score at Day 14 | Baseline | 4.8 Units on a scale | Standard Deviation 2.1 |
| Vehicle | Change From Baseline in LGS Total Score at Day 14 | Change from Baseline at Day 14 | -1.0 Units on a scale | Standard Deviation 1.8 |
Secondary
Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score
The investigator instilled an ophthalmic dye on the eye and rated corneal staining by type, extent/surface area, and depth. Each staining was rated on a 5-point scale from 0 to 4 (0=no staining/0% to 4=patch/\>45%/immediate diffuse stromal glow). The CFS Total Score (0-12) is the sum of the three individual ratings. A more negative percentage change indicates a greater amount of improvement.
Time frame: Baseline, up to Day 14
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score | Baseline | 4.9 Percent change | Standard Deviation 2.1 |
| Sodium Hyaluronate | Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score | Change from Baseline at Day 7 | -10.0 Percent change | Standard Deviation 40.3 |
| Sodium Hyaluronate | Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score | Change from Baseline at Day 14 | -19.3 Percent change | Standard Deviation 46.6 |
| Vehicle | Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score | Baseline | 4.8 Percent change | Standard Deviation 2 |
| Vehicle | Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score | Change from Baseline at Day 7 | -10.4 Percent change | Standard Deviation 36.9 |
| Vehicle | Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score | Change from Baseline at Day 14 | -16.1 Percent change | Standard Deviation 44.1 |
Secondary
Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score
For each of 5 common dry eye symptoms, the frequency (0-3) and intensity (0-100) scores were multiplied to obtain the symptom score (0-300). The 5 symptom scores were summed to obtain the Global Symptom Composite Index Score (0-1500). A more negative percentage change indicates a greater amount of improvement.
Time frame: Baseline, up to Day 14
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score | Baseline | 594.8 Percentage change | Standard Deviation 249.9 |
| Sodium Hyaluronate | Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score | Change from Baseline at Day 7 | -26.1 Percentage change | Standard Deviation 43.6 |
| Sodium Hyaluronate | Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score | Change from Baseline at Day 14 | -40.1 Percentage change | Standard Deviation 44.9 |
| Vehicle | Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score | Baseline | 608.4 Percentage change | Standard Deviation 258 |
| Vehicle | Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score | Change from Baseline at Day 7 | -22.4 Percentage change | Standard Deviation 43.2 |
| Vehicle | Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score | Change from Baseline at Day 14 | -36.3 Percentage change | Standard Deviation 44.4 |
Secondary
Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score
The subject completed a questionnaire and rated the intensity of five common dry eye symptoms. Intensity was rated on a visual analog scale from 0-100 (0=no symptoms to 100=severe symptoms). The GSI Total Score (0 to 500) is the sum of the five individual ratings. A more negative percentage change indicates a greater amount of improvement.
Time frame: Baseline, up to Day 14
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score | Baseline | 294.2 Percent change | Standard Deviation 80.8 |
| Sodium Hyaluronate | Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score | Change from Baseline at Day 7 | -18.9 Percent change | Standard Deviation 34.1 |
| Sodium Hyaluronate | Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score | Change from Baseline at Day 14 | -31.6 Percent change | Standard Deviation 37.7 |
| Vehicle | Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score | Baseline | 295.8 Percent change | Standard Deviation 82.5 |
| Vehicle | Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score | Change from Baseline at Day 7 | -15.4 Percent change | Standard Deviation 34.5 |
| Vehicle | Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score | Change from Baseline at Day 14 | -26.9 Percent change | Standard Deviation 38.4 |
Secondary
Percentage Change From Baseline in Schirmer I Score
The investigator placed a paper strip on the eye under the lower lid and left it in place for 5 minutes. The Schirmer I Score was the length of the strip wetted by the tears (0-35 millimeters). A more positive percentage change indicates a greater amount of improvement.
Time frame: Baseline, up to Day 14
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Hyaluronate | Percentage Change From Baseline in Schirmer I Score | Baseline | 9.7 Percent change | Standard Deviation 8.6 |
| Sodium Hyaluronate | Percentage Change From Baseline in Schirmer I Score | Change from Baseline at Day 7 | 52.1 Percent change | Standard Deviation 195.2 |
| Sodium Hyaluronate | Percentage Change From Baseline in Schirmer I Score | Change from Baseline at Day 14 | 60.3 Percent change | Standard Deviation 273.2 |
| Vehicle | Percentage Change From Baseline in Schirmer I Score | Baseline | 10.1 Percent change | Standard Deviation 8.5 |
| Vehicle | Percentage Change From Baseline in Schirmer I Score | Change from Baseline at Day 7 | 40.6 Percent change | Standard Deviation 139.8 |
| Vehicle | Percentage Change From Baseline in Schirmer I Score | Change from Baseline at Day 14 | 47.0 Percent change | Standard Deviation 170.7 |
Secondary
Proportion of Improved Scores on the Global Impact on Dry Eye Syndrome on Daily Life (GIDL) Rating
The subject was asked on a questionnaire, Please consider how your dry eyes feel when doing daily activities such as working on the computer, watching television, reading, and driving. Based on this, please rate the impact of your dry eye symptoms on your daily life, and responded on a 4-point scale from 0-3 (0=Absent to 3=Severe). Improved was defined as a change in score of \<0 from baseline. Proportion is reported as a percentage of participants. A greater percentage of subjects reporting a lower score indicates an improvement.
Time frame: Baseline, Up to Day 14
Population: Modified Intent-to-Treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sodium Hyaluronate | Proportion of Improved Scores on the Global Impact on Dry Eye Syndrome on Daily Life (GIDL) Rating | Day 7 | 31.0 Percentage of Participants |
| Sodium Hyaluronate | Proportion of Improved Scores on the Global Impact on Dry Eye Syndrome on Daily Life (GIDL) Rating | Day 14 | 42.7 Percentage of Participants |
| Vehicle | Proportion of Improved Scores on the Global Impact on Dry Eye Syndrome on Daily Life (GIDL) Rating | Day 7 | 26.5 Percentage of Participants |
| Vehicle | Proportion of Improved Scores on the Global Impact on Dry Eye Syndrome on Daily Life (GIDL) Rating | Day 14 | 38.0 Percentage of Participants |