Trial Outcomes & Findings for Dry Eye Assessment and Management Study (NCT NCT02128763)

Last Updated: 2022-07-19

Results Overview

Average of Ocular Surface Disease Index (OSDI) scores from 6 and 12 months minus average of values from screening and eligibility confirmation visits. OSDI scores range from 0 to 100, with a score of 0 indicating no ocular discomfort and higher scores indicating greater symptom severity. The minimal clinically meaningful change in score is 10 points.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

535 participants

Primary outcome timeframe

12 months

Results posted on

2022-07-19

Participant Flow

Participant milestones

Participant milestones
Measure	Omega-3 Supplements Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo Olive oil-5 gelcaps per day containing a total of 5 grams of refined olive oil Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Overall Study STARTED	349	186
Overall Study COMPLETED	329	170
Overall Study NOT COMPLETED	20	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Omega-3 Supplements Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo Olive oil-5 gelcaps per day containing a total of 5 grams of refined olive oil Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Overall Study Death	1	0
Overall Study Lost to Follow-up	19	16

Baseline Characteristics

Dry Eye Assessment and Management Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omega-3 Supplements n=349 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo n=186 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps	Total n=535 Participants Total of all reporting groups
Age, Continuous	58.3 years STANDARD_DEVIATION 13.5 • n=5 Participants	57.5 years STANDARD_DEVIATION 12.6 • n=7 Participants	58.0 years STANDARD_DEVIATION 13.2 • n=5 Participants
Sex: Female, Male Female	284 Participants n=5 Participants	150 Participants n=7 Participants	434 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	36 Participants n=7 Participants	101 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	44 Participants n=5 Participants	24 Participants n=7 Participants	68 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	302 Participants n=5 Participants	161 Participants n=7 Participants	463 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	39 Participants n=5 Participants	25 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) White	265 Participants n=5 Participants	133 Participants n=7 Participants	398 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	27 Participants n=5 Participants	15 Participants n=7 Participants	42 Participants n=5 Participants
Region of Enrollment United States	349 participants n=5 Participants	186 participants n=7 Participants	535 participants n=5 Participants
OSDI Score	44.6 units on a scale STANDARD_DEVIATION 14.1 • n=5 Participants	44.1 units on a scale STANDARD_DEVIATION 14.6 • n=7 Participants	44.1 units on a scale STANDARD_DEVIATION 14.2 • n=5 Participants
Brief Ocular Discomfort Inventory (BODI) Score	33.2 units on a scale STANDARD_DEVIATION 15.5 • n=5 Participants	33.4 units on a scale STANDARD_DEVIATION 16.3 • n=7 Participants	33.2 units on a scale STANDARD_DEVIATION 15.8 • n=5 Participants
EPA level in red cells	0.63 percentage of total fatty acids STANDARD_DEVIATION 0.43 • n=5 Participants	0.56 percentage of total fatty acids STANDARD_DEVIATION 0.35 • n=7 Participants	0.60 percentage of total fatty acids STANDARD_DEVIATION 0.40 • n=5 Participants
DHA level in red blood cells at baseline	3.91 percentage of total fatty acids STANDARD_DEVIATION 1.17 • n=5 Participants	3.85 percentage of total fatty acids STANDARD_DEVIATION 1.11 • n=7 Participants	3.9 percentage of total fatty acids STANDARD_DEVIATION 1.1 • n=5 Participants
Oleic Acid (OA) level in red cells	11.11 percentage of total fatty acids STANDARD_DEVIATION 1.24 • n=5 Participants	11.10 percentage of total fatty acids STANDARD_DEVIATION 1.38 • n=7 Participants	11.1 percentage of total fatty acids STANDARD_DEVIATION 1.3 • n=5 Participants
Tear Break Up Time (TBUT)	3.1 seconds STANDARD_DEVIATION 1.4 • n=5 Participants	3.1 seconds STANDARD_DEVIATION 1.6 • n=7 Participants	3.1 seconds STANDARD_DEVIATION 1.5 • n=5 Participants
Schimer's Test	9.3 mm STANDARD_DEVIATION 6.2 • n=5 Participants	10.2 mm STANDARD_DEVIATION 7.0 • n=7 Participants	9.8 mm STANDARD_DEVIATION 7.2 • n=5 Participants
Conjunctival Staining	3.1 units on a scale STANDARD_DEVIATION 1.4 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 1.4 • n=7 Participants	3.0 units on a scale STANDARD_DEVIATION 1.4 • n=5 Participants
Corneal Staining	4.0 point score STANDARD_DEVIATION 2.9 • n=5 Participants	3.7 point score STANDARD_DEVIATION 2.4 • n=7 Participants	3.9 point score STANDARD_DEVIATION 2.7 • n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=329 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=170 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Mean of Change From Baseline in Ocular Surface Disease Index (OSDI) Score at 6 and 12 Months	-13.9 units on a scale Standard Deviation 15.6	-12.5 units on a scale Standard Deviation 18.2

SECONDARY outcome

Timeframe: 12 months

Number of participants with at least a 10 point decrease from baseline in Ocular Surface Disease Index (OSDI). Change is the average score at 6 and 12 months minus the average score at the screening and eligibility confirmation visits. OSDI scores range from 0 to 100, with a score of 0 indicating no ocular discomfort and higher scores indicating greater symptom severity. A negative change score = improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=329 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=170 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Greater Than or Equal to 10 Point Decrease in Ocular Surface Disease Index (OSDI) (at Least 10 Point Improvement in Symptoms)	202 Participants	91 Participants

SECONDARY outcome

Timeframe: 12 months

Brief Ocular Discomfort Index (BODI) Pain Interference subscale scores range from 0 to 100, with higher scores indicating greater discomfort. Change is the average score at 6 and 12 months minus the average score at the screening and eligibility confirmation visits. A negative change score = improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=329 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=170 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Brief Ocular Discomfort Index (BODI) Pain Interference Subscale	-9.4 score on a scale Standard Deviation 15.0	-8.9 score on a scale Standard Deviation 16.2

SECONDARY outcome

Timeframe: 12 months

Medical Outcomes Study 36--Item Short Form Health Survey (SF-36) Physical Health Subscale. Subscale range is 0-100, with higher scores indicating better self reported physical health-related quality of life. Change is the average score at 6 and 12 months minus the average score at the screening and eligibility confirmation visits. A positive change score = improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=329 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=170 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change From Baseline in SF-36 Physical Health Subscale	0.1 score on a scale Standard Deviation 6.9	0.1 score on a scale Standard Deviation 6.3

SECONDARY outcome

Timeframe: 12 months

Medical Outcomes Study 26--Item Short Form Health Survey (SF-36) Mental Health Subscale. Mental Health subscale range is 0-100 with higher scores indicating better self reported mental health. Change is the average score at 6 and 12 months minus the average score at the screening and eligibility confirmation visits. A positive change score = improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=329 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=170 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change From Baseline in SF-36 Mental Health Subscale	-0.9 score on a scale Standard Deviation 6.3	0.4 score on a scale Standard Deviation 7.0

SECONDARY outcome

Timeframe: 12 months

Population: Data are missing for 20 subjects in the Omega 3 group and 15 subjects in the placebo group.

Change in EPA levels in red blood cells - percentage points. Change is the average level at 6 and 12 months minus the level at the eligibility confirmation visit. (Blood was not drawn at the screening visit.) If subjects are compliant, higher EPA levels in red blood cells in the Omega 3 group are expected and no change is expected in the placebo group. Data are missing for 20 subjects in the Omega 3 group and 15 subjects in the placebo group because blood was not drawn at the visit.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=309 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=155 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Compliance With the Study Treatment Protocol as Measured by Change in Blood Levels of EPA	2.2 percentage of fatty acids in blood cells Standard Deviation 1.2	0.0 percentage of fatty acids in blood cells Standard Deviation 0.2

SECONDARY outcome

Timeframe: 12 months

Population: Data are missing for 20 subjects in the Omega 3 group and 15 subjects in the placebo group.

Change in DHA levels in red blood cells - percentage points. Change is the average score at 6 and 12 months minus the average score at eligibility confirmation visit (blood was not drawn at the screening visit. If compliant, higher DHA levels in red blood cells in the Omega 3 group is expected and no change is expected in the placebo group. Data are missing for 20 subjects in the Omega 3 group and 15 subjects in the placebo group.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=309 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=155 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Compliance With the Study Treatment Protocol as Measured by Change in Blood Levels of DHA	1.6 percentage of fatty acids in blood cells Standard Deviation 1.2	0.0 percentage of fatty acids in blood cells Standard Deviation 0.2

SECONDARY outcome

Timeframe: 12 months

Population: Data are missing for 20 subjects in the Omega 3 group and 15 subjects in the placebo group

Change in Oleic Acid (from olive oil) levels in red blood cells - percentage points. Change is the average score at 6 and 12 months minus the average score at eligibility confirmation visit. (Blood was not drawn at the screening visit.) Data are missing for 20 subjects in the Omega 3 group and 15 subjects in the placebo group because blood was not drawn.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=309 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=155 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Compliance With the Study Treatment Protocol as Measured by Change in Blood Levels of Oleic Acid	-0.1 percentage of oleic acid in blood cells Standard Deviation 1.0	-0.1 percentage of oleic acid in blood cells Standard Deviation 1.0

SECONDARY outcome

Timeframe: 12 months

Population: Among eyes that qualified for the study.

Average change from 6 and 12 months minus average of values from screening and eligibility confirmation visits among eyes that qualified for the study. Scores range between 0-6, with higher scores indicate more severity. A negative change indicates improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=629 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=327 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Conjunctival Staining Score	-0.4 units on a scale Standard Deviation 1.1	-0.4 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: 12 months

Population: among eligible eyes

The Schirmer's test measures the production of tears by an eye as measured by mm of wetting of a strip of paper attached to the lower lid for 5 minutes. Scores range from 0 to 30 or more mm. Lower scores indicate more severe dry eye. Change is the average change from 6 and 12 months minus average of values from screening and eligibility confirmation visits among eyes that qualified for the study.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=629 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=327 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Schirmer's Test mm	0.4 mm Standard Deviation 5.3	0.3 mm Standard Deviation 5.0

SECONDARY outcome

Timeframe: 12 months

Population: Measure is eyes, not people.

Average of values from 6 and 12 months minus average of values from screening and eligibility confirmation visits. Possible range of scores is 0-\>20. Low values indicate greater severity. A positive change score = improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=629 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=327 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Tear Film Break up Time, in Seconds	0.7 seconds Standard Deviation 2.1	0.6 seconds Standard Deviation 1.6

SECONDARY outcome

Timeframe: 12 months

Population: Average change from 6 and 12 months minus average of values from screening and eligibility confirmation visits among eyes that quality that qualified for the study

Average change from 6 and 12 months minus average of values from screening and eligibility confirmation visits among eyes that quality that qualified for the study. Possible range of scores is 0-15; higher scores indicate more severity. A negative change indicates improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=629 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=327 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Corneal Fluorescein Staining Score	-0.6 units on a scale Standard Deviation 1.9	-0.7 units on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: 12 months

Population: Each eye measured separately. Total are numbers of eyes assessed, not subjects.

Visual acuity scores of 0-100 correspond to Snellen visual acuity levels of worse than 20/800 to 20/10, respectively. Higher change score = improved visual acuity.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=656 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=340 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Visual Acuity	-0.5 score on a scale Standard Deviation 5.0	-0.2 score on a scale Standard Deviation 4.8

SECONDARY outcome

Timeframe: 12 months

Population: Data are missing for 5 subjects in the omega -3 group and 6 subjects in the placebo group

Subjects with change in number of treatments used for dry eye disease, n.,(%)

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=324 Participants Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=164 Participants Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Use of Artificial Tears and Other Treatments for Dry Eye Disease Fewer treatments used, with no additions	171 Participants	93 Participants
Change in Use of Artificial Tears and Other Treatments for Dry Eye Disease No Change	80 Participants	36 Participants
Change in Use of Artificial Tears and Other Treatments for Dry Eye Disease ≤ treatments used, with ≥1 treatment switched	40 Participants	23 Participants
Change in Use of Artificial Tears and Other Treatments for Dry Eye Disease More treatments used	33 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Each eye measured separately

Eye pressure is measured in millimeters of mercury (mm Hg). Normal eye pressure ranges from 12-22 mm Hg, and eye pressure of greater than 22 mm Hg is considered higher than normal. Included as a safety measure.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=658 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=340 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Intraocular Pressure (IOP)- mm Hg	0.0 mmHg Standard Deviation 2.3	0.3 mmHg Standard Deviation 2.4

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Each eye is measured separately. Total are number of eyes assessed, not subjects. Tear Break up Time by Keratography was only measured at the 13 clinical centers that owned an Oculus Keratograph machine; therefore the number of participants analyzed for this measure is less than the overall number of study participants.

Tear breakup time (TBUT) is used to assess for evaporative dry eye disease. In this measure, TBUT is measured using the keratograph machine. TBUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. Change is the average of values from 6 and 12 months minus average of values from screening and eligibility confirmation visits.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=290 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=149 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Tear Break up Time by Keratography	-0.5 seconds Standard Deviation 6.7	-0.5 seconds Standard Deviation 6.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Each eye measured separately. Total are number of eyes assessed, not subjects. Tear Meniscus Height by Keratography was only measured at the 13 clinical centers that owned an Oculus Keratograph machine; therefore, the number of participants analyzed for this measure is less than the overall number of study participants.

The purpose of the tear film is to reduce evaporation of natural tears. Assessment of the tear film meniscus is a quantitative measurement of tear film quantity. In this measure, TMH is measured using the keratograph machine. Change is the average of values from 6 and 12 months minus average of values from screening and eligibility confirmation visits.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=317 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=162 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Tear Meniscus Height( TMH) by Keratography	0.00 mm Standard Deviation 0.16	-0.01 mm Standard Deviation 0.14

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Each eye measured separately. Total are number of eyes assessed, not subjects. Change in redness measured by keratography was only performed at the 13 clinical centers that owned an Oculus Keratograph machine; therefore, the number of participants analyzed for this measure is less than the overall number of study participants.

Change in ocular redness as measured using the keratograph machine. Change is the average of values from 6 and 12 months minus average of values from screening and eligibility confirmation visits. Title of the Scale used to measure outcome: Oculus Keratograph 5M R-scan, Scale Ranges: 0.0-4.0. A lower number indicates a better outcome (less redness).

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=273 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=145 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Redness by Keratography	-0.00 score on a scale Standard Deviation 0.34	-0.01 score on a scale Standard Deviation 0.40

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Each eye is measured separately. Total are number of eyes assessed, not subjects.Tear Osmolarity was only performed at the 18 clinical centers that owned a Tearlab osmolarity machine; therefore the number of participants analyzed for this measure is less than the overall number of study participants.

Tear osmolarity measures the salt content of the tears. Higher the osmolarity indicate more severe dry eye. Change is the average of values from 6 and 12 months minus average of values from screening and eligibility confirmation visits. A lower change score indicates improvement.

Outcome measures

Outcome measures
Measure	Omega-3 Supplements n=424 eyes Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo (5 Gms of Refined Olive Oil/Day) n=212 eyes Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Change in Tear Osmolarity	-0.7 mOsms/L Standard Deviation 21.5	3.6 mOsms/L Standard Deviation 18.3

Adverse Events

Omega-3 Supplements

Serious events: 21 serious events

Other events: 0 other events

Deaths: 1 deaths

Placebo

Serious events: 15 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Maureen G. Maguire, PhD

University of Pennsylvania

Phone: 215-615-1501

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Omega-3 Supplements n=349 participants at risk Total 2000 mg EPA and 1000 mg DHA per day taken in 5 gelcaps Omega-3 supplements: 2000 mg EPA and 1000 mg DHA per day	Placebo n=186 participants at risk Olive oil-5 gelcaps per day Placebo: Olive oil gelcaps manufactured to mimic Omega-3 gelcaps
Cardiac disorders ATRIAL FIBRILLATION	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Cardiac disorders ATRIAL FLUTTER	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Gastrointestinal disorders COLITIS	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Gastrointestinal disorders COLONIC OBSTRUCTION	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Gastrointestinal disorders DYSPEPSIA	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Hepatobiliary disorders GALLBLADER PAIN	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Immune system disorders HYPERSENSITIVITY	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Infections and infestations ABDOMINAL INFECTION	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Infections and infestations OSTEOMYELITIS	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Infections and infestations SKIN INFECTION	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Injury, poisoning and procedural complications FALL	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Injury, poisoning and procedural complications HIP FRACTURE	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Injury, poisoning and procedural complications SUBDURAL HAEMATOMA	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Musculoskeletal and connective tissue disorders CHONDROCALCINOSIS PYROPHOSPHATE	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Musculoskeletal and connective tissue disorders NECK PAIN	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CHRONIC MYELOID LEUKAEMIA	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LYMPHOMA	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Nervous system disorders FACIAL PALSY	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Psychiatric disorders PSYCHOTIC DISORDER	0.29% 1/349 • Number of events 2 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Renal and urinary disorders HYDRONEPHROSIS	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Respiratory, thoracic and mediastinal disorders PNEUMONIA ASPIRATION	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures ARTHRODESIS	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures CHOLECYSTECTOMY	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	1.1% 2/186 • Number of events 2 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures COLECTOMY	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures GASTROINTESTINAL ENDOSCOPIC THERAPY	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures HYSTERECTOMY	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures KNEE ARTHROPLASTY	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures OVARIAN CYSTECTOMY	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Surgical and medical procedures PARATHYROIDECTOMY	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Vascular disorders DEEP VEIN THROMBOSIS	0.00% 0/349 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.54% 1/186 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Vascular disorders HYPERTENSION	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA	0.29% 1/349 • Number of events 1 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.	0.00% 0/186 • AE data were collected from the safety visit to 12 months The AE reporting period was the from the screening visit to the end of the study follow-up (12 months). At the last visit, subjects were instructed to report any subsequent event(s) occurring within 30 days that the subject or a physician, believed might reasonably be related to study treatment. Subjects who withdrew early were contacted by the Clinic Coordinator 30 days after their last visit to ascertain whether any AEs occurred.