SYSTANE® BALANCE Symptoms (OSDI) & Inflammatory Biomarkers

• ClinicalTrials.gov Identifier: NCT01733732
• Recruitment Status: Completed
• First Posted: November 27, 2012
• Results First Posted: November 4, 2014
• Last Update Posted: June 29, 2018
• Sponsor: Alcon Research
• Information provided by (Responsible Party): Alcon Research

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Dry Eye Syndrome
• Interventions: Other: SYSTANE® BALANCE Lubricant Eye Drops; Other: SYSTANE® Gel
• Enrollment: 54

Participant Flow

Recruitment Details	Subjects were recruited from 1 study center located in the US.
Pre-assignment Details	A total of 54 subjects were screened and randomized. This reporting group includes all randomized subjects (54).

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Period Title: Overall Study
Started	27	27
Completed	25	27
Not Completed	2	0
Reason Not Completed
Adverse Event	1	0
Did not attend all study visits	1	0

Baseline Characteristics

Arm/Group Title		Systane Balance	Systane Gel	Total
Arm/Group Description		One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days	Total of all reporting groups
Overall Number of Baseline Participants		27	27	54
Baseline Analysis Population Description		This analysis group includes all randomized subjects.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	27 participants	27 participants	54 participants
		62.3 (14.5)	63.8 (12.8)	63.0 (13.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants	27 participants	54 participants
	Female	17 63.0%	16 59.3%	33 61.1%
	Male	10 37.0%	11 40.7%	21 38.9%

Outcome Measures

1. Primary Outcome

Title	Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit
Description	The Ocular Surface Disease Index (OSDI) is a 12-question validated questionnaire used to measure ocular symptoms, visual function, and environmental factors that may affect a patient's vision. The OSDI scoring scale ranges from 0 to 100. The lower the score, the more symptomatic relief from dry eye symptoms a patient experiences. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates a perceived improvement in ocular comfort.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of subjects with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Mean (Standard Deviation); Unit of Measure: units on a scale
Change from baseline at Day 14, n=25, 27	-7.85 (18.19)	-12.58 (19.05)
Change from baseline at Day 30, n=27, 27	-10.23 (21.72)	-16.74 (21.13)

2. Secondary Outcome

Title	Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) by Visit
Description	BCVA (with spectacles or other visual corrective devices) was determined using an ETDRS or modified EDTRS chart and measured in logMAR (logarithm of the minimum angle of resolution). Baseline-adjusted logMAR values were tabulated; a negative number change from baseline indicates better visual acuity. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of eyes with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Mean (Standard Deviation); Unit of Measure: LogMAR
Change from baseline at Day 14, n=50, 53	-0.02 (0.06)	-0.01 (0.04)
Change from baseline at Day 30, n=54, 51	-0.02 (0.06)	-0.02 (0.06)

3. Secondary Outcome

Title	Percentage of Eyes With Normal Slit-lamp Assessment
Description	An undilated slit lamp exam was performed to examine the regions of the eye: orbit/lids, conjunctiva, cornea, anterior chamber, iris and lens. Each region was graded normal or abnormal. The percentage of eyes with normal assessments by region is reported. Each eye was assessed individually. Both eyes were included in the tabulation.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. The actual sample size used in calculating the outcome measure may be smaller due to missing responses and/or visit attendance.

Arm/Group Title	Systane Balance, Day 0	Systane Balance, Day 14	Systane Balance, Day 30	Systane Gel, Day 0	Systane Gel, Day 14	Systane Gel, Day 30
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27	27	27	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	54	54	54	54	54	54
Measure Type: Number; Unit of Measure: percentage of eyes
Orbit / Lids	0.0	0.0	0.0	0.0	0.0	0.0
Conjunctiva	92.6	96.0	96.3	96.3	100.0	100.0
Cornea	92.6	92.0	92.6	92.6	92.6	92.6
Anterior chamber	100.0	100.0	100.0	100.0	100.0	100.0
Iris	94.4	94.0	94.4	100.0	100.0	100.0
Lens	44.4	44.0	44.4	51.9	51.9	51.9

4. Secondary Outcome

Title	Meibomian Gland Expression
Description	Meibomian gland expression (ie, pressing on the meibomian glands to excrete oil) was performed by the investigator during undilated slit lamp examination and graded on a 4-point scale where 0=normal, clear oil expressed and 3=congealed or no material expressed. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of eyes with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	54	54
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline (Day 0), n=54, 54	1.4 (0.60)	1.6 (0.77)
Day 14, n=50, 54	1.2 (0.59)	1.3 (0.59)
Day 30, n=54, 54	1.2 (0.59)	1.3 (0.68)

5. Secondary Outcome

Title	Mean Change From Baseline in Non-invasive Keratographic Tear Break up Time (NIKBUT) by Visit
Description	NIKBUT (time required for dry spots to appear on the surface of the eye after blinking) was measured in seconds using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of eyes with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	54	54
Mean (Standard Deviation); Unit of Measure: seconds
Change from baseline at Day 14, n=45, 54	0.587 (6.696)	-0.325 (4.557)
Change from baseline at Day 30, n=49, 52	-0.914 (5.697)	1.261 (6.633)

6. Secondary Outcome

Title	Mean Change From Baseline in Tear Meniscus Height (TMH) by Visit
Description	TMH (the distance between the line of reflection along the top of the tear prism to the edge of the eyelid) was measured in millimeters using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of eyes with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	54	54
Mean (Standard Deviation); Unit of Measure: millimeters
Change from baseline at Day 14, n=50, 54	0.146 (0.165)	0.089 (0.181)
Change from baseline at Day 30, n=54, 52	0.140 (0.168)	0.165 (0.242)

7. Secondary Outcome

Title	Mean Change From Baseline in Ocular Surface Staining by Visit
Description	Ocular surface staining (damage to the ocular surface) was assessed using non-toxic ophthalmic dye during slit-lamp review. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The ocular staining score ranges from 0 to 3. The lower the score, the less signs of dry eye disease a patient exhibits. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. The actual sample size used in calculating the outcome measure may be smaller due to missing responses and/or visit attendance.

Arm/Group Title	Systane Balance, Change From Baseline at Day 14	Systane Balance, Change From Baseline at Day 30	Systane Gel, Change From Baseline at Day 14	Systane Gel, Change From Baseline at Day 30
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	25	27	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	50	54	54	54
Mean (Standard Deviation); Unit of Measure: units on a scale
Corneal staining	-1.0 (2.0)	-0.9 (2.3)	-1.3 (2.2)	-1.6 (2.4)
Conjunctival staining	-0.7 (1.4)	-0.7 (1.4)	-0.9 (1.5)	-1.0 (1.4)

8. Secondary Outcome

Title	Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30
Description	A tear sample was collected and cytokine (small proteins) levels were analyzed using a High Sensitive Human Cytokine MilliPlex kit and measured in picograms/milliliter (pg/mL). Baseline-adjusted scores were tabulated; a negative number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of subjects with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Mean (Standard Deviation); Unit of Measure: pg/mL
IFN-gamma, n=24, 25	2.680 (14.366)	15.146 (65.229)
IL-1beta, n=24, 25	0.192 (1.161)	0.335 (2.515)
IL-6, n=24, 25	0.902 (5.009)	0.735 (16.364)
TNF-alpha, n=24, 25	-0.058 (1.713)	0.693 (5.727)

9. Secondary Outcome

Title	Mean Change From Baseline for % HLA-DR Inflammatory Biomarker Expression at Day 30
Description	Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. The number of cells expressing the inflammatory marker HLA-DR (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as HLA-DR score at Day 30 minus HLA-DR score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.
Time Frame	Baseline (Day 0), Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	54	54
Mean (Standard Deviation); Unit of Measure: percentage of cells
	-0.751 (1.934)	-0.300 (0.844)

10. Secondary Outcome

Title	Mean Change From Baseline mRNA for % HLA-DR and TNF-alpha Gene Expression at Day 30
Description	Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. Total RNA was isolated. The number of cells expressing the inflammatory marker (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as score at Day 30 minus score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.
Time Frame	Baseline (Day 0), Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of subjects with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Mean (Standard Deviation); Unit of Measure: percentage of cells
HLA-DR, n=19, 25	0.079 (2.199)	0.019 (1.027)
TNF-alpha, n=20, 23	-0.061 (0.313)	0.009 (0.140)

11. Secondary Outcome

Title	Mean Change From Baseline in Dry Eye Status as Measured by the Schirmer's Test by Visit
Description	Dry eye status was assessed using the Schirmer's test. The investigator placed a paper strip on the eye under the lower lid for a specified time period. The length of the strip wetted by the tears was measured in millimeters. Baseline-adjusted values were tabulated; a positive number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of eyes with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	54	54
Mean (Standard Deviation); Unit of Measure: millimeters
Change from baseline at Day 14, n=50, 54	-0.3 (7.0)	2.8 (7.9)
Change from baseline at Day 30, n=54, 54	4.6 (8.5)	2.6 (8.2)

12. Secondary Outcome

Title	Mean Change From Baseline in Intraocular Pressure (IOP) by Visit
Description	IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline-adjusted values were tabulated. Each eye was assessed individually. Both eyes contributed to the mean.
Time Frame	Baseline (Day 0), Day 14, Day 30

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of eyes with non-missing values at the specific time point for each arm group, respectively.

Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description:	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
Overall Number of Participants Analyzed	27	27
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	54	54
Mean (Standard Deviation); Unit of Measure: mmHg
Change from baseline at Day 14, n=50, 54	0.0 (0.5)	0.2 (0.9)
Change from baseline at Day 30, n=54, 54	0.1 (1.4)	-0.1 (0.2)

Adverse Events

Time Frame	Adverse events (AEs) were collected for the duration of the study (7 months). This analysis group includes all subjects exposed to the test product.
Adverse Event Reporting Description	An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through volunteered and elicited comments from the subjects.
Arm/Group Title	Systane Balance	Systane Gel
Arm/Group Description	One drop in each eye 4 times a day for 30 days	One drop in each eye 4 times a day for 30 days
All-Cause Mortality
	Systane Balance	Systane Gel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Systane Balance	Systane Gel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/27 (0.00%)	1/27 (3.70%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis to central nervous system * 1	0/27 (0.00%)	1/27 (3.70%)
Nervous system disorders
Convulsion † 1	0/27 (0.00%)	1/27 (3.70%)
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Systane Balance	Systane Gel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/27 (0.00%)	0/27 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

• Name/Title: Abayomi Ogundele, Pharm.D, Global Brand Medical Affairs Lead
• Organization: Alcon Research, Ltd.
• Phone: 1-888-451-3937
• EMail: alcon.medinfo@alcon.com

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01733732
• Other Study ID Numbers: A00976
• First Submitted: November 21, 2012
• First Posted: November 27, 2012
• Results First Submitted: October 29, 2014
• Results First Posted: November 4, 2014
• Last Update Posted: June 29, 2018