Clinical Outcomes Following Treatment With Systane® Balance in Dry Eye Subjects

Evaluation of Clinical Outcomes Following Treatment With Systane® Balance in Dry Eye Subjects With Lipid Deficiency

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01967147

Enrollment

279

Registered

2013-10-22

Start date

2014-02-28

Completion date

2015-01-31

Last updated

2016-03-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dry Eye

Keywords

Dry eye, Lipid deficiency, Tear film break-up time

Brief summary

The purpose of this study is to demonstrate the superior efficacy of Systane® Balance over Preservative-Free 0.9% Saline following 35 days of QID (4 times a day) dosing in treating dry eye subjects with lipid deficiency.

Detailed description

This study consisted of 4 visits conducted during 3 sequential phases: the Run-in Phase (which included a screening visit and run-in period), Treatment Phase I and Treatment Phase II. In Phase I, subjects were randomized to either Systane® Balance or Saline and dosed 4 times a day for 35 days. In Phase II (Day 35-90) subjects continued to dose with their assigned product on an as-needed basis.

Interventions

DRUGPropylene Glycol, 0.6% eye drops

Commercially available eye drops used during Treatment Phase

DRUGPreservative-free 0.9% Saline solution

Commercially available solution used as Run-in (1 drop in each eye 4 times a day for 15 days) and during Treatment Phase

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Must have all of the following in at least 1 eye at Screening: 1. Meibomian Gland Dysfunction (MGD) grading for Expressibility ≤ 2 and Meibum Quality ≤ 2, 2. The average of 3 measures of TFBUT ≤ 5 seconds, and 3. Unanesthetized Schirmer I test of ≥ 3 mm. * Must have an Ocular Surface Disease Index (OSDI) Score ≥ 18 at Visit 1 prior to randomization (ie, after 2 weeks of run-in with Preservative-Free 0.9% Saline administered 4 times a day). * Must have best-corrected visual acuity of 55 letters or better in each eye as assessed using an early treatment diabetic retinopathy study (ETDRS) chart (letter read method). * Physician diagnosis of dry eye at least 6 months prior to Screening visit. * Willing and able to attend all study visits. * Must sign a written informed consent form. * Other protocol-defined inclusion criteria may apply.

Exclusion criteria

* Subjects on topical ocular treatments containing benzalkonium chloride (BAK), or other products with known toxicity to the corneal surface, within 30 days of Screening. * Subjects who have started, stopped, or changed a lid hygiene regimen within 30 days of Screening. * Use of any artificial tears/lubricants/gels/rewetting drops within 4 hours of Screening. * Women of childbearing potential are excluded from participating in this study if they met any of the following conditions: * Currently pregnant, or * Test positive for pregnancy at Screening visit, or * Currently breast feeding, or * Are not in agreement to use adequate birth control methods to prevent pregnancy throughout the study. * Hypersensitivity to the use of any of the study products or allergy to any ingredient in the study products. * Has an active ocular allergy. * Any ocular abnormalities that could adversely affect the safety or efficacy outcome, including eyelid anomalies, corneal disorders, history of herpes simplex, etc. * Subjects taking any systemic medication known to cause dry eye unless they have been on stable therapy/dosage for at least 30 days prior to Screening and will remain on a stable dosage for the duration of the study. * History of any ocular or intraocular surgery (including periocular Botox injections), eyelid surgery, keratorefractive procedure, corneal transplant and its variants, or serious ocular trauma within 1 year of Screening. * Active ocular infection (bacterial, viral or fungal), active inflammation not associated with dry eye such as uveitis, iritis, active blepharitis, active allergic conjunctivitis, etc. * Subjects with punctal plug insertion or diathermy procedure initiated within 30 days of Screening. * Any significant illnesses that could be expected to interfere with the study parameters. * Subjects with active oculodermal rosacea with meibomian gland dysfunction. * Participation in an investigational drug or device trial within 30 days of Screening. * Contact lens use within 30 days prior to Screening, or unwilling to avoid contact lens use during the course of the study. * Unwilling to avoid the use of additional artificial tears/lubricants/gels/rewetting drops (other than the assigned study medication) throughout the course of the study. * Other protocol-defined

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in TFBUT at Day 35	Baseline (Day 0), Day 35	TFBUT (the time required for dry spots to appear on the corneal surface after blinking) was assessed by the investigator using ophthalmic dye and a biomicroscope and measured in seconds. Subjects were dosed in the office 1 hour ±10 minutes prior to TFBUT assessment. A shorter TFBUT indicates a higher likelihood of dry eye symptoms. A positive change indicates an improvement in TFBUT. One eye (study eye) contributed to the analysis.

Secondary

Measure	Time frame	Description
Change From Baseline in TOSS Score at Day 35	Baseline (Day 0), Day 35	The TOSS score (a cumulative cornea and conjunctival staining score) was assessed by the investigator using ophthalmic dye and a biomicroscope. Three areas of the ocular surface were graded for dryness on a 0-5 scale (0=Absent, 5=Severe), with a resultant overall score of 0-15. A negative change indicates an improvement in dry eye-related staining. One eye (study eye) contributed to the analysis.
Change From Baseline in OSDI Score at Day 35	Baseline (Day 0), Day 35	The OSDI is a 12-item quality of life questionnaire designed to assess ocular surface symptoms, their severity, and their impact on the subject's ability to function. Each item was scored by the subject on a 0-4 Likert-type scale (0=None, 4=All of the Time), with a resultant overall score of 0-100 (0=no disability, 100=complete disability). A negative change number represents a perceived improvement in ocular health.
Change From Baseline in IDEEL Treatment Effectiveness Score at Day 35	Baseline (Day 0), Day 35	The IDEEL is a 10-item questionnaire designed to assess the subject's general satisfaction with treatment use. The subject responded to treatment effectiveness questions (Questions 2-5) using a 0-4 Likert-type scale, where 0=None of the time and 4=All of the time. The IDEEL treatment effectiveness score was calculated as the sum of the responses from Questions 2-5 divided by the number of questions (2-5) answered, multiplied by 25, for a resultant overall score of 0-100. A positive change number represents perceived improvement.
Change From Baseline in IDEEL Treatment Inconvenience Score at Day 35	Baseline (Day 0), Day 35	The IDEEL is a 10-item questionnaire designed to assess the subject's general satisfaction with treatment use. The subject responded to treatment inconvenience questions (Questions 6, 8-10) using a 0-4 Likert-type scale, where 0=All of the time and 4=None of the time. The IDEEL treatment inconvenience score was calculated as the sum of the responses from Questions 6, 8-10 divided by the number of questions (6, 8-10) answered, multiplied by 25, for a resultant overall score of 0-100. A positive change number represents perceived improvement.

Participant flow

Recruitment details

Subjects were recruited from 14 study centers located in France, 4 study centers located in Germany, 3 study centers located in Spain, 3 study centers located in the Netherlands, 4 study centers located in the UK, 4 study centers located in Italy, and 3 study centers located in Poland.

Pre-assignment details

Of the 279 subjects enrolled, 40 were exited as screen failures prior to randomization. An additional 25 were discontinued prior to randomization, following the outcome of the interim analysis. This reporting group includes all randomized subjects (214).

Participants by arm

Arm	Count
Systane Balance Propylene Glycol, 1 drop in each eye, 4 times per day, during Phase I, followed by 1 drop in each eye as needed during Phase II	112
Saline Saline solution, 1 drop in each eye, 4 times/day, during Phase I, followed by 1 drop in each eye as needed during Phase II	102
Total	214

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	5	2
Overall Study	Lack of Efficacy	1	4
Overall Study	Lost to Follow-up	1	2
Overall Study	Non-compliance with Study Drug	0	3
Overall Study	Other	4	5
Overall Study	Withdrawal by Subject	2	4

Baseline characteristics

Characteristic	Total	Systane Balance	Saline
Age, Continuous	59.0 years STANDARD_DEVIATION 14.7	59.5 years STANDARD_DEVIATION 15.5	58.4 years STANDARD_DEVIATION 14
IDEEL Treatment Inconvenience	75.60 units on a scale STANDARD_DEVIATION 23.4	76.61 units on a scale STANDARD_DEVIATION 22.08	74.48 units on a scale STANDARD_DEVIATION 24.85
Impact of Dry Eye on Everyday Life (IDEEL) Treatment Effectiveness Score	45.35 units on a scale STANDARD_DEVIATION 27.52	44.63 units on a scale STANDARD_DEVIATION 27.32	46.15 units on a scale STANDARD_DEVIATION 27.86
Ocular surface disease index (OSDI)	39.30 units on a scale STANDARD_DEVIATION 17.42	40.24 units on a scale STANDARD_DEVIATION 17.48	38.27 units on a scale STANDARD_DEVIATION 17.39
Sex: Female, Male Female	163 Participants	91 Participants	72 Participants
Sex: Female, Male Male	51 Participants	21 Participants	30 Participants
Tear Film Break-up Time (TFBUT)	3.72 seconds STANDARD_DEVIATION 1.48	3.73 seconds STANDARD_DEVIATION 1.37	3.71 seconds STANDARD_DEVIATION 1.59
Total Ocular Surface Staining (TOSS) Score	3.40 units on a scale STANDARD_DEVIATION 2.25	3.45 units on a scale STANDARD_DEVIATION 2.14	3.35 units on a scale STANDARD_DEVIATION 2.38

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 279	6 / 110	1 / 100
serious Total, serious adverse events	0 / 279	2 / 110	2 / 100

Outcome results

Primary

Change From Baseline in TFBUT at Day 35

TFBUT (the time required for dry spots to appear on the corneal surface after blinking) was assessed by the investigator using ophthalmic dye and a biomicroscope and measured in seconds. Subjects were dosed in the office 1 hour ±10 minutes prior to TFBUT assessment. A shorter TFBUT indicates a higher likelihood of dry eye symptoms. A positive change indicates an improvement in TFBUT. One eye (study eye) contributed to the analysis.

Time frame: Baseline (Day 0), Day 35