A Safety and Efficacy Study of OPTIVE FUSION™ With VISMED® Multi for the Management of Dry Eye

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02117687
• Collaborator: (none)
• Enrollment: 80
• Locations: 2
• Arms: 2
• Actual Duration (Months): 10.1
• Patients Per Site: 40
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of OPTIVE FUSION™ compared to VISMED® Multi for the management of dry eye.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes; Keratoconjunctivitis Sicca	Drug: carboxymethylcellulose 0.5%/glycerin 0.9%; Drug: sodium hyaluronate 0.18%	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Actual Study Start Date: May 14, 2014
• Actual Primary Completion Date: Jan 27, 2015
• Actual Study Completion Date: Mar 17, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: OPTIVE FUSION™ 1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	Drug: carboxymethylcellulose 0.5%/glycerin 0.9%; 1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.; Other Names: OPTIVE FUSION™
Active Comparator: VISMED® Multi 1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	Drug: sodium hyaluronate 0.18%; 1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.; Other Names: VISMED® Multi

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Global Ocular Staining Score in the Study Eye [Baseline, Day 35]

   Global ocular staining of the study eye was graded from 0 to 15 and was the sum of corneal fluorescein staining severity, nasal conjunctiva lissamine green staining severity, and temporal conjunctiva lissamine green staining severity. Staining of the cornea followed ocular administration of fluorescein dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Staining of the conjunctiva followed ocular administration of lissamine green dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Conjunctival staining was evaluated in two zones, nasal and temporal.

Secondary Outcome Measures

1. Change From Baseline in Global Ocular Staining Score in the Study Eye [Baseline, Month 3]

   Global ocular staining of the study eye was graded from 0 to 15 and was the sum of corneal fluorescein staining severity, nasal conjunctiva lissamine green staining severity, and temporal conjunctiva lissamine green staining severity. Staining of the cornea followed ocular administration of fluorescein dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Staining of the conjunctiva followed ocular administration of lissamine green dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Conjunctival staining was evaluated in two zones, nasal and temporal.

2. Change From Baseline in Ocular Surface Disease Index© (OSDI) Score [Baseline, Day 35]

   The OSDI is a 12-question survey for patients to document their dry eye disease symptoms on a 5-point scale (0=none of the time and 4=all of the time). Higher scores represent greater disability. Scores are totaled over the 12 questions and converted to a score of 0-100 (0=no disability and 100=complete disability). A negative number change from baseline represents an improvement and a positive number change from baseline represents a worsening.

3. Change From Baseline in the Schirmer Test in the Study Eye [Baseline, Day 35]

   The Schirmer's Test measures the rate of secretion of tears produced by the study eye over 5 minutes. The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye. A positive number change from baseline indicates an increase in tears (improvement) and a negative number change from baseline indicates a decrease in tears (worsening).

4. Subject Assessment of Dry Eye Symptoms on a 5-Point Scale [Baseline, Day 35, Month 3]

   Subjects assess dry eye symptoms on a 5-point scale (none, mild, moderate, severe, very severe).

5. Subject Global Assessment of Treatment Efficacy on a 5-Point Scale [Baseline, Day 35, Month 3]

   Subjects assess global treatment efficacy compared to baseline on a 5-point scale (much worse, worse, about the same, improved, much improved).

6. Subject Assessment of Treatment Acceptability on a 5-Point Scale [Day 35]

   Subjects assess treatment acceptability (likability and comfort) on a 5-point scale (strongly agree, agree, neither agree nor disagree, disagree, strongly disagree).

7. Investigator Global Assessment of Treatment Efficacy on a 4-Point Scale [Day 35, Month 3]

   Investigators assess global treatment efficacy on a 4-point scale (very satisfactory, satisfactory, poor, very poor).

8. Change From Baseline in Tear Break-up Time (TBUT) in the Study Eye [Baseline, Day 35]

   TBUT is the time required for dry spots to appear on the surface of the eye after blinking in the worse eye. The longer it takes, the more stable the tear film. A short TBUT is a sign of poor tear film. A positive number change from baseline indicates an increase in TBUT (improvement) and a negative number change from baseline indicates a decrease in TBUT (worsening).

9. Work Productivity and Activity Impairment Questionnaire Score [Baseline, Day 35, Month 3]

   The Work Productivity and Activity questionnaire assesses the effect of dry eye on the ability of subjects to work and perform regular activities on a scale from 0 to 10 during the past 7 days (0=dry eye had no effect on my work/daily activities to 10=dry eye completely prevented me from working/doing my daily activities). Since not all subjects were in full time employment during the study, not all items of the questionnaire were applicable to all subjects at each visit. Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.

10. Change From Baseline in Corneal Staining in the Study Eye [Baseline, Day 35, Month 3]

    The cornea is the transparent front part of the eye which covers the iris and pupil. Staining of the cornea followed ocular administration of fluorescein dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). A negative number change from baseline represents a decrease in corneal staining (improvement) and a positive number change from baseline represents an increase in corneal staining (worsening).

11. Change From Baseline in Conjunctival Staining in the Study Eye [Baseline, Day 35, Month 3]

    The conjunctiva is the clear membrane covering the white surface of the eye. Staining of the conjunctiva followed ocular administration of lissamine green dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining) in the temporal and nasal locations. A negative number change from baseline represents a decrease in corneal staining (improvement) and a positive number change from baseline represents an increase in corneal staining (worsening).

12. Conjunctival Hyperaemia in the Study Eye [Baseline, Day 35, Month 3]

    Macroscopic conjunctival hyperemia (eye redness) is graded in the study eye on a 5-point scale (none, trace, mild, moderate, severe).

13. Study Product Use [Day 8, Day 35, Month 3]

    The number of times the study product is administered per day is recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Use of artificial tears for dry eye in both eyes for at least 3 months

• Use of preservative-free artificial tears at least twice daily for 2 weeks;

Exclusion Criteria:

• Cataract, laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (PRK) surgery in the last 12 months

• Use of punctal plugs or contact lenses in the last month

• Active ocular allergy within last 2 years

• Best corrected visual acuity (BCVA) less than 20/200 in either eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Paris		France
2		London		United Kingdom

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Labetoulle M, Chiambaretta F, Shirlaw A, Leaback R, Baudouin C. Osmoprotectants, carboxymethylcellulose and hyaluronic acid multi-ingredient eye drop: a randomised controlled trial in moderate to severe dry eye. Eye (Lond). 2017 Oct;31(10):1409-1416. doi: 10.1038/eye.2017.73. Epub 2017 Apr 28. Erratum in: Eye (Lond). 2017 Oct;31(10 ):1512.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02117687
• Other Study ID Numbers: MAF-AGN-OPH-DE-016
• First Posted: Apr 21, 2014
• Last Update Posted: Apr 18, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis; Carboxymethylcellulose Sodium; Hyaluronic Acid; Glycerol

Study Results

Participant Flow

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Period Title: Overall Study
STARTED	40	40
COMPLETED	39	36
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi	Total
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	Total of all reporting groups
Overall Participants	40	40	80
Age, Customized (Number) [Number]
<65 years	17 42.5%	25 62.5%	42 52.5%
≥65 years	23 57.5%	15 37.5%	38 47.5%
Sex: Female, Male (Count of Participants)
Female	36 90%	33 82.5%	69 86.3%
Male	4 10%	7 17.5%	11 13.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Global Ocular Staining Score in the Study Eye
Description	Global ocular staining of the study eye was graded from 0 to 15 and was the sum of corneal fluorescein staining severity, nasal conjunctiva lissamine green staining severity, and temporal conjunctiva lissamine green staining severity. Staining of the cornea followed ocular administration of fluorescein dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Staining of the conjunctiva followed ocular administration of lissamine green dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Conjunctival staining was evaluated in two zones, nasal and temporal.
Time Frame	Baseline, Day 35

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline	5.2 (1.11)	5.2 (1.21)
Change from Baseline at Day 35	-1.5 (1.54)	-1.6 (1.54)

2. Secondary Outcome

Title	Change From Baseline in Global Ocular Staining Score in the Study Eye
Description	Global ocular staining of the study eye was graded from 0 to 15 and was the sum of corneal fluorescein staining severity, nasal conjunctiva lissamine green staining severity, and temporal conjunctiva lissamine green staining severity. Staining of the cornea followed ocular administration of fluorescein dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Staining of the conjunctiva followed ocular administration of lissamine green dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). Conjunctival staining was evaluated in two zones, nasal and temporal.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline	5.2 (1.11)	5.2 (1.21)
Change from Baseline at Day 35	-2.5 (2.23)	-2.4 (2.24)

3. Secondary Outcome

Title	Change From Baseline in Ocular Surface Disease Index© (OSDI) Score
Description	The OSDI is a 12-question survey for patients to document their dry eye disease symptoms on a 5-point scale (0=none of the time and 4=all of the time). Higher scores represent greater disability. Scores are totaled over the 12 questions and converted to a score of 0-100 (0=no disability and 100=complete disability). A negative number change from baseline represents an improvement and a positive number change from baseline represents a worsening.
Time Frame	Baseline, Day 35

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline	45.5 (22.02)	44.4 (17.60)
Change from Baseline at Day 35	-10.3 (13.51)	-12.9 (13.13)

4. Secondary Outcome

Title	Change From Baseline in the Schirmer Test in the Study Eye
Description	The Schirmer's Test measures the rate of secretion of tears produced by the study eye over 5 minutes. The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye. A positive number change from baseline indicates an increase in tears (improvement) and a negative number change from baseline indicates a decrease in tears (worsening).
Time Frame	Baseline, Day 35

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline	11.1 (10.22)	8.7 (7.29)
Change from Baseline at Day 35	0.1 (7.74)	1.0 (5.44)

5. Secondary Outcome

Title	Subject Assessment of Dry Eye Symptoms on a 5-Point Scale
Description	Subjects assess dry eye symptoms on a 5-point scale (none, mild, moderate, severe, very severe).
Time Frame	Baseline, Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline Stinging/Burning - None (N=32,28)	0	1
Baseline Stinging/Burning - Mild (N=32,28)	7	4
Baseline Stinging/Burning - Moderate (N=32,28)	17	13
Baseline Stinging/Burning - Severe (N=32,28)	7	9
Baseline Stinging/Burning - Very Severe (N=32,28)	1	1
Day 35 Stinging/Burning - None	5	2
Day 35 Stinging/Burning - Mild	12	8
Day 35 Stinging/Burning - Moderate	17	17
Day 35 Stinging/Burning - Severe	1	3
Day 35 Stinging/Burning - Very Severe	0	1
Month 3 Stinging/Burning - None	5	6
Month 3 Stinging/Burning - Mild	14	5
Month 3 Stinging/Burning - Moderate	15	13
Month 3 Stinging/Burning - Severe	1	6
Month 3 Stinging/Burning - Very Severe	0	1
Baseline Itching - None (N=32,28)	6	5
Baseline Itching - Mild (N=32,28)	8	7
Baseline Itching - Moderate (N=32,28)	12	1
Baseline Itching - Severe (N=32,28)	6	3
Baseline Itching - Very Severe (N=32,28)	0	2
Day 35 Itching- None	10	8
Day 35 Itching- Mild	8	7
Day 35 Itching- Moderate	15	13
Day 35 Itching- Severe	2	2
Day 35 Itching- Very Severe	0	1
Month 3 Itching- None	10	10
Month 3 Itching- Mild	12	8
Month 3 Itching- Moderate	11	9
Month 3 Itching- Severe	2	3
Month 3 Itching- Very Severe	0	1
Baseline Sandiness/Grittiness - None (N=32,28)	2	1
Baseline Sandiness/Grittiness - Mild (N=32,28)	6	5
Baseline Sandiness/Grittiness - Moderate (N=32,28)	19	12
Baseline Sandiness/Grittiness - Severe (N=32,28)	5	8
Bsln Sandiness/Grittiness-Very Severe (N=32,28)	0	2
Day 35 Sandiness/Grittiness - None	7	4
Day 35 Sandiness/Grittiness - Mild	13	8
Day 35 Sandiness/Grittiness - Moderate	14	13
Day 35 Sandiness/Grittiness - Severe	1	4
Day 35 Sandiness/Grittiness - Very Severe	0	2
Month 3 Sandiness/Grittiness - None	7	8
Month 3 Sandiness/Grittiness - Mild	17	4
Month 3 Sandiness/Grittiness - Moderate	9	15
Month 3 Sandiness/Grittiness - Severe	2	3
Month 3 Sandiness/Grittiness - Very Severe	0	1
Baseline Blurred Vision - None (N=32,28)	11	10
Baseline Blurred Vision - Mild (N=32,28)	8	7
Baseline Blurred Vision - Moderate (N=32,28)	10	7
Baseline Blurred Vision - Severe (N=32,28)	3	3
Baseline Blurred Vision - Very Severe (N=32,28)	0	1
Day 35 Blurred Vision - None	16	13
Day 35 Blurred Vision - Mild	10	9
Day 35 Blurred Vision - Moderate	8	7
Day 35 Blurred Vision - Severe	1	1
Day 35 Blurred Vision - Very Severe	0	1
Month 3 Blurred Vision - None	20	14
Month 3 Blurred Vision - Mild	7	9
Month 3 Blurred Vision - Moderate	6	5
Month 3 Blurred Vision - Severe	1	1
Month 3 Blurred Vision - Very Severe	1	2
Baseline Dryness - None (N=32,28)	1	1
Baseline Dryness - Mild (N=32,28)	2	2
Baseline Dryness - Moderate (N=32,28)	13	10
Baseline Dryness - Severe (N=32,28)	13	12
Baseline Dryness - Very Severe (N=32,28)	3	3
Day 35 Dryness - None	4	3
Day 35 Dryness - Mild	8	5
Day 35 Dryness - Moderate	16	14
Day 35 Dryness - Severe	7	7
Day 35 Dryness - Very Severe	0	2
Month 3 Dryness - None	2	3
Month 3 Dryness - Mild	12	5
Month 3 Dryness - Moderate	17	14
Month 3 Dryness - Severe	4	6
Month 3 Dryness - Very Severe	0	3
Baseline Light Sensitivity - None (N=32,28)	1	2
Baseline Light Sensitivity - Mild (N=32,28)	4	8
Baseline Light Sensitivity - Moderate (N=32,28)	14	6
Baseline Light Sensitivity - Severe (N=32,28)	9	7
Baseline Light Sensitivity - Very Severe (N=32,28)	4	5
Day 35 Light Sensitivity - None	5	2
Month 3 Light Sensitivity - Severe	5	8
Month 3 Light Sensitivity - Very Severe	1	3
Day 35 Light Sensitivity - Mild	6	7
Day 35 Light Sensitivity - Moderate	18	11
Day 35 Light Sensitivity - Severe	5	7
Day 35 Light Sensitivity - Very Severe	1	4
Month 3 Light Sensitivity - None	5	2
Month 3 Light Sensitivity - Mild	16	10
Month 3 Light Sensitivity - Moderate	8	8
Baseline Painful or Sore - None (N=31,28)	0	1
Baseline Painful or Sore - Mild (N=31,28)	12	8
Baseline Painful or Sore - Moderate (N=31,28)	15	13
Baseline Painful or Sore - Severe (N=31,28)	4	4
Baseline Painful or Sore - Very Severe (N=31,28)	0	2
Day 35 Painful or Sore - None	5	5
Day 35 Painful or Sore - Mild	20	9
Day 35 Painful or Sore - Moderate	9	13
Day 35 Painful or Sore - Severe	1	2
Day 35 Painful or Sore - Very Severe	0	2
Month 3 Painful or Sore - None	5	9
Month 3 Painful or Sore - Mild	17	3
Month 3 Painful or Sore - Moderate	10	16
Month 3 Painful or Sore - Severe	2	2
Month 3 Painful or Sore - Very Severe (N=34,31)	0	1
Baseline Other - None (N=3,1)	0	0
Baseline Other - Mild (N=3,1)	0	0
Baseline Other - Moderate (N=3,1)	1	0
Baseline Other - Severe (N=3,1)	0	0
Baseline Other - Very Severe (N=3,1)	0	1
Day 35 Other - None (N=1,3)	0	0
Day 35 Other - Mild (N=1,3)	0	0
Day 35 Other - Moderate (N=1,3)	1	1
Day 35 Other - Severe (N=1,3)	0	1
Day 35 Other - Very Severe (N=1,3)	0	1
Month 3 Other - None (N=1,3)	0	1
Month 3 Other - Mild (N=1,3)	0	0
Month 3 Other - Moderate (N=1,3)	1	0
Month 3 Other - Severe (N=1,3)	0	1
Month 3 Other - Very Severe (N=1,3)	0	1

6. Secondary Outcome

Title	Subject Global Assessment of Treatment Efficacy on a 5-Point Scale
Description	Subjects assess global treatment efficacy compared to baseline on a 5-point scale (much worse, worse, about the same, improved, much improved).
Time Frame	Baseline, Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Day 35 - Much Worse	0	0
Day 35 - Worse	0	3
Day 35 - About the Same	12	11
Day 35 - Improved	21	14
Day 35 - Much Improved	2	3
Month 3 - Much Worse	0	1
Month 3 - Worse	0	3
Month 3 - About the Same	11	10
Month 3 - Improved	19	13
Month 3 - Much Improved	5	4

7. Secondary Outcome

Title	Subject Assessment of Treatment Acceptability on a 5-Point Scale
Description	Subjects assess treatment acceptability (likability and comfort) on a 5-point scale (strongly agree, agree, neither agree nor disagree, disagree, strongly disagree).
Time Frame	Day 35

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Liked - Strongly Agree (N=35,30)	14	8
Liked - Agree (N=35,30)	12	10
Liked - Neither Agree nor Disagree (N=35,30)	6	9
Liked - Disagree (N=35,30)	2	2
Liked - Strongly Disagree (N=35,30)	1	1
Comfortable - Strongly Agree	9	9
Comfortable - Agree	16	13
Comfortable - Neither Agree nor Disagree	7	6
Comfortable - Disagree	2	2
Comfortable - Strongly Disagree	1	1

8. Secondary Outcome

Title	Investigator Global Assessment of Treatment Efficacy on a 4-Point Scale
Description	Investigators assess global treatment efficacy on a 4-point scale (very satisfactory, satisfactory, poor, very poor).
Time Frame	Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Day 35 - Very Satisfactory	13	8
Day 35 - Satisfactory	17	19
Day 35 - Poor	5	4
Day 35 - Very Poor	0	0
Month 3 - Very Satisfactory	15	10
Month 3 - Satisfactory	15	11
Month 3 - Poor	5	9
Month 3 - Very Poor	0	1

9. Secondary Outcome

Title	Change From Baseline in Tear Break-up Time (TBUT) in the Study Eye
Description	TBUT is the time required for dry spots to appear on the surface of the eye after blinking in the worse eye. The longer it takes, the more stable the tear film. A short TBUT is a sign of poor tear film. A positive number change from baseline indicates an increase in TBUT (improvement) and a negative number change from baseline indicates a decrease in TBUT (worsening).
Time Frame	Baseline, Day 35

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline	5.52 (2.575)	5.75 (3.146)
Change from Baseline at Day 35	0.6 (1.66)	0.7 (2.00)

10. Secondary Outcome

Title	Work Productivity and Activity Impairment Questionnaire Score
Description	The Work Productivity and Activity questionnaire assesses the effect of dry eye on the ability of subjects to work and perform regular activities on a scale from 0 to 10 during the past 7 days (0=dry eye had no effect on my work/daily activities to 10=dry eye completely prevented me from working/doing my daily activities). Since not all subjects were in full time employment during the study, not all items of the questionnaire were applicable to all subjects at each visit. Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time Frame	Baseline, Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, who did not adhere to a pre-defined list of protocol violation criteria, and who had data for this data point

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline - Work Productivity (N=11,13)	3.09 (1.921)	3.46 (3.382)
Baseline - Activity Impairment	3.91 (2.035)	4.35 (2.550)
Day 35 - Work Productivity (N=11,9)	2.55 (1.809)	2.33 (1.936)
Day 35 - Activity Impairment (N=34,31)	3.09 (2.065)	3.52 (2.393)
Month 3 - Work Productivity (N=11,10)	1.82 (0.982)	2.40 (2.066)
Month 3 - Activity Impairment	2.14 (1.630)	2.77 (2.232)

11. Secondary Outcome

Title	Change From Baseline in Corneal Staining in the Study Eye
Description	The cornea is the transparent front part of the eye which covers the iris and pupil. Staining of the cornea followed ocular administration of fluorescein dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining). A negative number change from baseline represents a decrease in corneal staining (improvement) and a positive number change from baseline represents an increase in corneal staining (worsening).
Time Frame	Baseline, Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline	1.7 (0.68)	1.9 (0.65)
Change from Baseline at Day 35	-0.4 (0.77)	-0.7 (0.83)
Change from Baseline at Month 3	-0.8 (0.84)	-0.9 (1.04)

12. Secondary Outcome

Title	Change From Baseline in Conjunctival Staining in the Study Eye
Description	The conjunctiva is the clear membrane covering the white surface of the eye. Staining of the conjunctiva followed ocular administration of lissamine green dye and was graded on a 6-point scale (0=no staining to 5=diffuse staining) in the temporal and nasal locations. A negative number change from baseline represents a decrease in corneal staining (improvement) and a positive number change from baseline represents an increase in corneal staining (worsening).
Time Frame	Baseline, Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline - Temporal	1.7 (0.64)	1.6 (0.81)
Change from Baseline at Day 35 - Temporal	-0.5 (0.66)	-0.5 (0.81)
Change from Baseline at Month 3 - Temporal	-0.8 (0.79)	-0.8 (0.92)
Baseline - Nasal	1.9 (0.66)	1.7 (0.70)
Change from Baseline at Day 35 - Nasal	-0.6 (0.65)	-0.5 (0.68)
Change from Baseline at Month 3 - Nasal	-0.9 (0.97)	-0.7 (0.87)

13. Secondary Outcome

Title	Conjunctival Hyperaemia in the Study Eye
Description	Macroscopic conjunctival hyperemia (eye redness) is graded in the study eye on a 5-point scale (none, trace, mild, moderate, severe).
Time Frame	Baseline, Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Baseline - None	8	8
Baseline - Trace	13	11
Baseline - Mild	13	10
Baseline - Moderate	1	2
Baseline Severe	0	0
Day 35 - None	17	12
Day 35 - Trace	9	10
Day 35 - Mild	9	8
Day 35 - Moderate	0	1
Day 35 - Severe	0	0
Month 3 - None	22	14
Month 3 - Trace	8	7
Month 3 - Mild	5	9
Month 3 - Moderate	0	1
Month 3 - Severe	0	0

14. Secondary Outcome

Title	Study Product Use
Description	The number of times the study product is administered per day is recorded.
Time Frame	Day 8, Day 35, Month 3

Outcome Measure Data

Analysis Population Description

Per Protocol: all randomized subjects who received at least one dose of the study product, had at least one follow-up visit, and who did not adhere to a pre-defined list of protocol violation criteria

Arm/Group Title	OPTIVE FUSION™	VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.	1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
Measure Participants	35	31
Day 8	3.63 (1.190)	3.47 (0.900)
Day 35	3.77 (1.285)	3.39 (0.761)
Month 3	3.71 (1.178)	3.42 (0.958)

Adverse Events

Adverse Event Reporting Description	The Safety Population included all randomized subjects treated with at least one dose of study product. The Safety Population was used to assess adverse events (AEs) and serious adverse events (SAEs).
Arm/Group Title	OPTIVE FUSION™		VISMED® Multi
Arm/Group Description	1-2 drops OPTIVE FUSION™ (carboxymethylcellulose 0.5%/glycerin 0.9%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.		1-2 drops VISMED® Multi (sodium hyaluronate 0.18%) in each eye as needed at least 2 times and no more than 6 times daily, for 3 months.
All Cause Mortality
	OPTIVE FUSION™		VISMED® Multi
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	OPTIVE FUSION™		VISMED® Multi
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		1/40 (2.5%)
Cardiac disorders
Pericarditis	0/40 (0%)		1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	OPTIVE FUSION™		VISMED® Multi
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/40 (10%)		6/40 (15%)
Eye disorders
Dry Eye	0/40 (0%)		2/40 (5%)
Eye Discharge	0/40 (0%)		2/40 (5%)
Eye Irritation	2/40 (5%)		2/40 (5%)
Eye Pruritus	2/40 (5%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.