Trial Outcomes & Findings for SYSTANE® BALANCE Symptoms (OSDI) & Inflammatory Biomarkers (NCT NCT01733732)

NCT ID: NCT01733732

Last Updated: 2018-06-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 54 participants
• Primary outcome timeframe: Baseline (Day 0), Day 14, Day 30
• Results posted on: 2018-06-29

Participant Flow

Subjects were recruited from 1 study center located in the US.

A total of 54 subjects were screened and randomized. This reporting group includes all randomized subjects (54).

Participant milestones

Measure	Systane Balance One drop in each eye 4 times a day for 30 days	Systane Gel One drop in each eye 4 times a day for 30 days
Overall Study STARTED	27	27
Overall Study COMPLETED	25	27
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Systane Balance One drop in each eye 4 times a day for 30 days	Systane Gel One drop in each eye 4 times a day for 30 days
Overall Study Adverse Event	1	0
Overall Study Did not attend all study visits	1	0

Baseline Characteristics

SYSTANE® BALANCE Symptoms (OSDI) & Inflammatory Biomarkers

Baseline characteristics by cohort

Measure	Systane Balance n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Gel n=27 Participants One drop in each eye 4 times a day for 30 days	Total n=54 Participants Total of all reporting groups
Age, Continuous	62.3 years STANDARD_DEVIATION 14.5 • n=5 Participants	63.8 years STANDARD_DEVIATION 12.8 • n=7 Participants	63.0 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Gel n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit Change from baseline at Day 14, n=25, 27	-7.85 units on a scale Standard Deviation 18.19	-12.58 units on a scale Standard Deviation 19.05	—	—	—	—
Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit Change from baseline at Day 30, n=27, 27	-10.23 units on a scale Standard Deviation 21.72	-16.74 units on a scale Standard Deviation 21.13	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Gel n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) by Visit Change from baseline at Day 14, n=50, 53	-0.02 LogMAR Standard Deviation 0.06	-0.01 LogMAR Standard Deviation 0.04	—	—	—	—
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) by Visit Change from baseline at Day 30, n=54, 51	-0.02 LogMAR Standard Deviation 0.06	-0.02 LogMAR Standard Deviation 0.06	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 n=54 eyes One drop in each eye 4 times a day for 30 days
Percentage of Eyes With Normal Slit-lamp Assessment Orbit / Lids	0.0 percentage of eyes	0.0 percentage of eyes	0.0 percentage of eyes	0.0 percentage of eyes	0.0 percentage of eyes	0.0 percentage of eyes
Percentage of Eyes With Normal Slit-lamp Assessment Conjunctiva	92.6 percentage of eyes	96.0 percentage of eyes	96.3 percentage of eyes	96.3 percentage of eyes	100.0 percentage of eyes	100.0 percentage of eyes
Percentage of Eyes With Normal Slit-lamp Assessment Cornea	92.6 percentage of eyes	92.0 percentage of eyes	92.6 percentage of eyes	92.6 percentage of eyes	92.6 percentage of eyes	92.6 percentage of eyes
Percentage of Eyes With Normal Slit-lamp Assessment Anterior chamber	100.0 percentage of eyes	100.0 percentage of eyes	100.0 percentage of eyes	100.0 percentage of eyes	100.0 percentage of eyes	100.0 percentage of eyes
Percentage of Eyes With Normal Slit-lamp Assessment Iris	94.4 percentage of eyes	94.0 percentage of eyes	94.4 percentage of eyes	100.0 percentage of eyes	100.0 percentage of eyes	100.0 percentage of eyes
Percentage of Eyes With Normal Slit-lamp Assessment Lens	44.4 percentage of eyes	44.0 percentage of eyes	44.4 percentage of eyes	51.9 percentage of eyes	51.9 percentage of eyes	51.9 percentage of eyes

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Meibomian Gland Expression Baseline (Day 0), n=54, 54	1.4 units on a scale Standard Deviation 0.60	1.6 units on a scale Standard Deviation 0.77	—	—	—	—
Meibomian Gland Expression Day 14, n=50, 54	1.2 units on a scale Standard Deviation 0.59	1.3 units on a scale Standard Deviation 0.59	—	—	—	—
Meibomian Gland Expression Day 30, n=54, 54	1.2 units on a scale Standard Deviation 0.59	1.3 units on a scale Standard Deviation 0.68	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline in Non-invasive Keratographic Tear Break up Time (NIKBUT) by Visit Change from baseline at Day 14, n=45, 54	0.587 seconds Standard Deviation 6.696	-0.325 seconds Standard Deviation 4.557	—	—	—	—
Mean Change From Baseline in Non-invasive Keratographic Tear Break up Time (NIKBUT) by Visit Change from baseline at Day 30, n=49, 52	-0.914 seconds Standard Deviation 5.697	1.261 seconds Standard Deviation 6.633	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline in Tear Meniscus Height (TMH) by Visit Change from baseline at Day 14, n=50, 54	0.146 millimeters Standard Deviation 0.165	0.089 millimeters Standard Deviation 0.181	—	—	—	—
Mean Change From Baseline in Tear Meniscus Height (TMH) by Visit Change from baseline at Day 30, n=54, 52	0.140 millimeters Standard Deviation 0.168	0.165 millimeters Standard Deviation 0.242	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=50 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline in Ocular Surface Staining by Visit Corneal staining	-1.0 units on a scale Standard Deviation 2.0	-0.9 units on a scale Standard Deviation 2.3	-1.3 units on a scale Standard Deviation 2.2	-1.6 units on a scale Standard Deviation 2.4	—	—
Mean Change From Baseline in Ocular Surface Staining by Visit Conjunctival staining	-0.7 units on a scale Standard Deviation 1.4	-0.7 units on a scale Standard Deviation 1.4	-0.9 units on a scale Standard Deviation 1.5	-1.0 units on a scale Standard Deviation 1.4	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Gel n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30 IFN-gamma, n=24, 25	2.680 pg/mL Standard Deviation 14.366	15.146 pg/mL Standard Deviation 65.229	—	—	—	—
Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30 IL-1beta, n=24, 25	0.192 pg/mL Standard Deviation 1.161	0.335 pg/mL Standard Deviation 2.515	—	—	—	—
Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30 IL-6, n=24, 25	0.902 pg/mL Standard Deviation 5.009	0.735 pg/mL Standard Deviation 16.364	—	—	—	—
Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30 TNF-alpha, n=24, 25	-0.058 pg/mL Standard Deviation 1.713	0.693 pg/mL Standard Deviation 5.727	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 30

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

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.

Outcome measures

Measure	Systane Balance n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline for % HLA-DR Inflammatory Biomarker Expression at Day 30	-0.751 percentage of cells Standard Deviation 1.934	-0.300 percentage of cells Standard Deviation 0.844	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Gel n=27 Participants One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline mRNA for % HLA-DR and TNF-alpha Gene Expression at Day 30 HLA-DR, n=19, 25	0.079 percentage of cells Standard Deviation 2.199	0.019 percentage of cells Standard Deviation 1.027	—	—	—	—
Mean Change From Baseline mRNA for % HLA-DR and TNF-alpha Gene Expression at Day 30 TNF-alpha, n=20, 23	-0.061 percentage of cells Standard Deviation 0.313	0.009 percentage of cells Standard Deviation 0.140	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline in Dry Eye Status as Measured by the Schirmer's Test by Visit Change from baseline at Day 14, n=50, 54	-0.3 millimeters Standard Deviation 7.0	2.8 millimeters Standard Deviation 7.9	—	—	—	—
Mean Change From Baseline in Dry Eye Status as Measured by the Schirmer's Test by Visit Change from baseline at Day 30, n=54, 54	4.6 millimeters Standard Deviation 8.5	2.6 millimeters Standard Deviation 8.2	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 14, Day 30

Population: 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.

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.

Outcome measures

Measure	Systane Balance n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Gel n=54 eyes One drop in each eye 4 times a day for 30 days	Systane Balance, Day 30 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 0 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 14 One drop in each eye 4 times a day for 30 days	Systane Gel, Day 30 One drop in each eye 4 times a day for 30 days
Mean Change From Baseline in Intraocular Pressure (IOP) by Visit Change from baseline at Day 14, n=50, 54	0.0 mmHg Standard Deviation 0.5	0.2 mmHg Standard Deviation 0.9	—	—	—	—
Mean Change From Baseline in Intraocular Pressure (IOP) by Visit Change from baseline at Day 30, n=54, 54	0.1 mmHg Standard Deviation 1.4	-0.1 mmHg Standard Deviation 0.2	—	—	—	—

Adverse Events

Systane Balance

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Systane Gel

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Systane Balance n=27 participants at risk One drop in each eye 4 times a day for 30 days	Systane Gel n=27 participants at risk One drop in each eye 4 times a day for 30 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis to central nervous system	0.00% 0/27 • Adverse events (AEs) were collected for the duration of the study (7 months). This analysis group includes all subjects exposed to the test product. 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.	3.7% 1/27 • Adverse events (AEs) were collected for the duration of the study (7 months). This analysis group includes all subjects exposed to the test product. 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.
Nervous system disorders Convulsion	0.00% 0/27 • Adverse events (AEs) were collected for the duration of the study (7 months). This analysis group includes all subjects exposed to the test product. 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.	3.7% 1/27 • Adverse events (AEs) were collected for the duration of the study (7 months). This analysis group includes all subjects exposed to the test product. 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.

Other adverse events

Adverse event data not reported

Additional Information

Abayomi Ogundele, Pharm.D, Global Brand Medical Affairs Lead

Alcon Research, Ltd.

Phone: 1-888-451-3937

Email: alcon.medinfo@alcon.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
• Publication restrictions are in place

Restriction type: OTHER