Sodium Hyaluronate Ophthalmic Solution, 0.18% for Treatment of Dry Eye Syndrome

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01382225
• Collaborator: (none)
• Enrollment: 1,936
• Arms: 2
• Duration (Months): 10

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndrome	Drug: Sodium Hyaluronate Ophthalmic Solution, 0.18%; Other: Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1936 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multicenter, Randomized, Controlled, Double-Masked Study of Safety and Efficacy of Sodium Hyaluronate Ophthalmic Solution, 0.18% in Dry Eye Syndrome
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sodium Hyaluronate Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Drug: Sodium Hyaluronate Ophthalmic Solution, 0.18%
Placebo Comparator: Vehicle Inactive ingredients, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Other: Vehicle; Inactive ingredients used as run-in and placebo comparator

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Michela Montecchi-Palmer, BS, Alcon Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01382225
• Other Study ID Numbers: C-09-045
• First Posted: Jun 27, 2011
• Last Update Posted: Jul 8, 2013
• Last Verified: May 1, 2013

• Keywords provided by Alcon Research: Dry eyes; Ocular discomfort
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Syndrome; Ophthalmic Solutions; Hyaluronic Acid

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 56 investigative sites in the United States.
Pre-assignment Detail	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).

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	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	Run-in, followed by Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Period Title: Overall Study
STARTED	725	729
COMPLETED	711	722
NOT COMPLETED	14	7

Baseline Characteristics

Arm/Group Title	Sodium Hyaluronate	Vehicle	Total
Arm/Group Description	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	Run-in, followed by Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Total of all reporting groups
Overall Participants	723	727	1450
Age, Customized (participants) [Number]
18-64 years	402 55.6%	392 53.9%	794 54.8%
≥65 years	321 44.4%	335 46.1%	656 45.2%
Sex: Female, Male (Count of Participants)
Female	590 81.6%	594 81.7%	1184 81.7%
Male	133 18.4%	133 18.3%	266 18.3%
Region of Enrollment (participants) [Number]
United States	723 100%	727 100%	1450 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Lissamine Green Staining (LGS) Total Score at Day 7
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	4.9 (2.2)	4.8 (2.1)
Change from Baseline at Day 7	-0.8 (1.8)	-0.7 (1.6)

2. Primary Outcome

Title	Change From Baseline in Global Symptom Frequency (GSF) Total Score at Day 7
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	8.9 (2.3)	9.1 (2.3)
Change from Baseline at Day 7	-1.6 (2.6)	-1.3 (2.4)

3. Secondary Outcome

Title	Change From Baseline in LGS Total Score at Day 14
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	4.9 (2.2)	4.8 (2.1)
Change from Baseline at Day 14	-1.2 (2.0)	-1.0 (1.8)

4. Secondary Outcome

Title	Change From Baseline in GSF Total Score at Day 14
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	8.9 (2.3)	9.1 (2.3)
Change from Baseline at Day 14	-2.3 (2.8)	-2.2 (2.8)

5. Secondary Outcome

Title	Percentage Change From Baseline in Corneal Fluorescein Staining (CFS) Total Score
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	4.9 (2.1)	4.8 (2.0)
Change from Baseline at Day 7	-10.0 (40.3)	-10.4 (36.9)
Change from Baseline at Day 14	-19.3 (46.6)	-16.1 (44.1)

6. Secondary Outcome

Title	Percentage Change From Baseline in Schirmer I Score
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	9.7 (8.6)	10.1 (8.5)
Change from Baseline at Day 7	52.1 (195.2)	40.6 (139.8)
Change from Baseline at Day 14	60.3 (273.2)	47.0 (170.7)

7. Secondary Outcome

Title	Percentage Change From Baseline in Global Symptom Intensity (GSI) Total Score
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	294.2 (80.8)	295.8 (82.5)
Change from Baseline at Day 7	-18.9 (34.1)	-15.4 (34.5)
Change from Baseline at Day 14	-31.6 (37.7)	-26.9 (38.4)

8. Secondary Outcome

Title	Percentage Change From Baseline in Global Symptom Composite Index (GSCI) Score
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Baseline	594.8 (249.9)	608.4 (258.0)
Change from Baseline at Day 7	-26.1 (43.6)	-22.4 (43.2)
Change from Baseline at Day 14	-40.1 (44.9)	-36.3 (44.4)

9. Secondary Outcome

Title	Proportion of Improved Scores on the Global Impact on Dry Eye Syndrome on Daily Life (GIDL) Rating
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat

Arm/Group Title	Sodium Hyaluronate	Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days	Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
Measure Participants	643	648
Day 7	31.0 4.3%	26.5 3.6%
Day 14	42.7 5.9%	38.0 5.2%

Adverse Events

Time Frame	Adverse events were collected for the duration of the study. The safety population includes all randomized subjects who receive exposure to study medication or had potential exposure.
Arm/Group Title	Sodium Hyaluronate		Vehicle
Arm/Group Description	Sodium Hyaluronate Ophthalmic Solution, 0.18%, 1-2 drops instilled in each eye 3-6 times a day for 14 days		Vehicle, 1-2 drops instilled in each eye 3-6 times a day for 14 days
All Cause Mortality
	Sodium Hyaluronate		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sodium Hyaluronate		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/723 (0.1%)		1/727 (0.1%)
Gastrointestinal disorders
Gastritis	1/723 (0.1%)		0/727 (0%)
Metabolism and nutrition disorders
Hyponatraemia	0/723 (0%)		1/727 (0.1%)
Psychiatric disorders
Mania	0/723 (0%)		1/727 (0.1%)
Other (Not Including Serious) Adverse Events
	Sodium Hyaluronate		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/723 (0%)		0/727 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.