CLINICAL TRIAL

Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing

Omega-3, Omega-5 And Omega-9 Cetylated Fatty Acid

Catherine M. Legaspi, MD, FPDS

Concepcion Esto, MD, DPDS; Madelaine M. Palmea, MD, DPCP

July 2016

Background:
Topical painkillers or analgesics are rubbed on the skin over painful muscles or joints. Although all are designed to
relieve pain, different products use different ingredients and some of them are counterirritants because they create a
burning or cooling sensation that distracts the brain from the pain. However, the concern of the increasing contact
dermatitis from tropical pain relievers has underscored the need to find a safer alternative.

Objectives:
a. This study aims to determine and compare the dermal safety of OLEIA Omega 3, 5, and 9 cetylated oil with
0.09 NaCl solution (Placebo) in the treatment of muscle and joint pains.
b. To determine the photoallergic potential of OLEIA Oil in the treatment of muscle and joint pains.
c. To monitor the development of adverse reactions during product usage over the duration of the study.

Results:
A total of eighty-four panelists completed the treatment protocol. OLEIA Oil and 0.09 NaCl solution-treated patients
showed equal results with no significant effect on the dermal irritant scoring in all parameters evaluated (p<0.001,
Fisher exact test).

Conclusion:
This study showed that OLEIA Cetylated Oil is dermal-safe, no irritant potential and well tolerated in the local skin
treatment of muscle and joint pains.

Key words:
topical analgesics, contact irritant, photoallergic potential, cetylated oil, randomized controlled trial
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Table of Contents

Introduction……………………………………………………………... Page 3

Methodology…………..………………………………………………... 4
Inclusion Criteria…………….………………………………….. 4
Exclusion Criteria…....……………………………...………….. 5

Outcome Measurements……………………………………………... 8

Standard Analysis………………….…………………………………...8

Results………….……...……………………………………………….. 8
Primary Irritancy Group…….………………………………….. 9
Photocontact Irritant Potential Group…..………...………….. 11
Cumulative Irritant Group…..………………………………….. 13

Conclusion…………..…...…………………………………………….. 17

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INTRODUCTION

Despite technological advances and thorough established treatments, pain

management continues to defy health professionals. The difficulties that
restrict therapeutic success such as increasing systemic side effects and
cognitive impairment of oral analgesics are the ultimate motivators for the
development of topical preparations.

Topical analgesics or anaesthetics are defined as liquids, gels, powders,

creams, semisolids, emulsions, patches, foams, or aerosols containing an
analgesic or anaesthetic agent. These topical pain killers are rubbed onto
the skin over painful muscles or joints. Although all are designed to relieve
pain, different products use different ingredients. And some of these are
counterirritants because they create a burning or cooling sensation that
distracts the mind from the pain. Most of counterirritants are chemicals that
can have potential dermal injury.

The increasing unintentional injuries represent a leading cause of morbidity

and mortality around the world for people of all age groups. Dermal safety
is one of the most understudied areas of public health (Krejci-Manwaring,
Kerchner, Feldman, Rapp & Rapp, 2006) despite recent research
documenting that dermatological threats are on the rise worldwide (Jardine
et al., 2012). While exposure to ambient solar radiation among vulnerable
populations accounts for a large proportion of skin traumas in the form of
cancer (Armstrong & Kricker, 2001; Mahé, Ly, Aymard & Dangou, 2003)
many other potential skin hazards also exist such as occupational-related
skin exposures (National Institute for Occupational Safety and Health, n.d.),
community skin exposures and skin damage resulting from practices such
as frequent rubbing of muscle and joint pain relievers. Considering the
potential harm that can occur from exposure to hazardous chemicals,

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comparatively little research attention has been given to the widespread

global practice of topical analgesics. It is the purpose of this study to
initiate skin safety evaluations of topical analgesics and to inspire
pharmaceuticals and drug developers to partner with skin authorities (PDS
doctors) in insuring dermal safety (the absence of contact sensitization,
phototoxicity, cumulative irritancy and hazardous effects) as part of the
present standard of care.

METHODOLOGY

A single-blind (outcome assessment), randomized, interventional parallel

assignment, and a placebo-controlled clinical trial were conducted over a
10-week period beginning July to September 2016 in three multi-center
OPD clinics (NEGH-QC, HealthHub-Makati and MMP Health Clinic-Clark).

One hundred two panelists, ages 18-70 were recruited mostly from
community and health work forces (nurses, security guards, janitors,
laboratory technicians and construction workers).

The inclusion and exclusion criteria were as follows:

Inclusion Criteria

1. Healthy male or female volunteers aged at least 18 years.

Good general, physical and mental health in the opinion of the
investigator or medically qualified designee.

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2. No clinically significant and relevant abnormalities in medical history

or upon physical examination.
3. Absence of any condition that could affect the volunteer’s safety or
well-being or their ability to understand and follow study procedures
and requirements.
4. Healthy volunteers who do not have excessive hair o the volar aspect
of the forearm(s).
5. Healthy volunteers should understand and be willing to fully comply
with all study procedures and restrictions.
6. Demonstrates understanding of the study and willingness to
participate as evidenced by voluntary written informed consent and
has received a signed and dated copy of the informed consent form.
7. Females of childbearing potential, using an effective contraceptive
method for at least one month before the beginning of the study, and
willing to use throughout the study.

Exclusion Criteria

1. Volunteers having recent history (within one year) of alcohol or other

substance abuse as determined by medical history.
2. Participation in another clinical study or receipt of an investigational
drug within 30 days of the screening visit.
3. Previous participation in similar study with similar products.
4. Volunteer has any visible skin disease at the site of application that,
in the opinion of the investigator, will interfere with the skin
assessments.

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5. Volunteer has current or relevant previous history of serious, severe

or unstable physical or psychiatric illness, or medical disorders such
as current or previous history of hepatic or renal diseases
(impairment) or peptic ulcer as determined by medical history.
6. Volunteer has a history of hypersensitivity (e.g. asthma,
bronchospasm, rhinitis, urticaria, nasal polyps) to aspirin, diclofenac,
other nonsteroidal anti-inflammatory drugs (NSAIDs), menthol or any
of the excipients in the test product(s).
7. Volunteer is receiving systemic or topical NSAIDs, other oral or
topical analgesics or antihistamine within 3 days of visit 1, or other
medication (such as corticosteroids within 3 weeks of visit 1) which,
in the opinion of the investigative personnel, will interfere with the
study results.
8. Female volunteers who are pregnant, planning to become pregnant
during the study or are breastfeeding.
9. Female volunteers who have positive pregnancy test.
10. Volunteers who are employees of the sponsor or study site or an
immediate family member (e.g. partner, offspring, parents, siblings or
sibling’s offspring) of such employees.
11. Any skin disorder at the test site that in the investigator’s judgement
can affect the readings of the test result.
12. Any concomitant medications that in the investigator’s judgement can
confound or alter test results or evaluation of the adverse events.

Once the subject was deemed eligible for the study, nature of the study
was explained to the subjects. The consent form was explained and duly
signed by the subject. The subjects were randomly distributed to one of
the two study groups using a randomization code generated from
CLINSTAT software.

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Intervention: The first 32 subjects/panelists were requested to undergo the

3-leveled study group (1) Primary Irritancy Test, (2) Photo Allergic Potential
Test, (3) Cumulative Irritancy Test. The remaining recruits proceeded
immediately to the Cumulative Irritancy Test.

Subjects enrolled in Primary Irritancy Test were randomly distributed to the

OLEIA Group and Placebo Group (0.9 NaCl solution). The investigator put
one drop of the solution on the right forearm which was then sealed with
Tegaderm plaster. They were requested to have the 24-hour patch test.
They were requested to return on the following day for the investigators to
record the results.

After applying the Tegaderm plaster on the right forearm, the

subjects/panelists proceeded to the Photo Allergic Potential Test. Using
their previous randomized grouping, a drop of the solution was put on the
left forearm and exposed with UVB light for 5 minutes. Results were
recorded immediately after the 5-minute test.

All panelists were subsequently enrolled in the Cumulative Irritancy Test.

They were instructed to apply the given solution liberally over aching joints
and muscles and instructed to report immediately if any irritations were
noted. They were also told to come and follow up weekly for two weeks.

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OUTCOME MEASUREMENTS

The primary outcome measured was the absence of clinical signs of dermal
irritation including (1) skin turning red, (2) welting up, (3) showing a rash,
(4) oozing skin, (5) symptoms of itchiness on the body sites where the
solution was applied. A standard severity grading scale (0=absent, 1=mild,
2=moderate, 3=severe) was used to rate each sign and symptom. The
panelists were required to note and report any other adverse side effects
using a standard questionnaire.

STANDARD ANALYSIS

All statistical computations were conducted using SPSS software.

Demographic variables and other baseline characteristics were
summarized by descriptive statistics. The Chi-Square test without
continuity correction was used to analyze discrete variables, and analysis
of variance was used for continuous variables to assess comparability
among the two treatment groups. Further, a Fisher’s exact test was used
to test the difference. All statistical tests were two-tailed with a significance
level of alpha=0.05.

RESULTS

A total of 102 panelists were recruited for this clinical trial but only 84
completed the treatment protocol and were included in the analysis. The
panelists were randomized to receive placebo (0.09 NaCl Solution) and
OLEIA. Of the first 32 recruits that underwent the Primary Irritancy Group,
27 (15 for OLEIA and 12 for Placebo) completed the 24-hour patch test.

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I. PRIMARY IRRITANCY GROUP

Table I: Demographic

Characteristics

Gender OLEIA GROUP PLACEBO p value

M 7 7 0.884

F 8 5

Mean Age 39.92 39.69 0.915

Table I shows the demographics that there were no significant differences

among the treatment groups with regard to gender and age.

The panelists were evaluated after 24 hours for the dermal irritancy scoring
(Table II). All or 100% of the panelists on both groups did not develop skin
redness, welting up, rash, oozing skin nor any symptoms of itchiness.

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Table II: Dermal Irritant Score

0-Absent 1-Mild 2-Moderate 3-Severe

OLEIA PLACEBO

0 15 (100%) 0 12 (100%)

1 1
Skin turning red
2 2

3 3

0 15 (100%) 0 12 (100%)

1 1
Welting up
2 2

3 3

0 15 (100%) 0 12 (100%)

1 1
Showing a rash
2 2

3 3

0 15 (100%) 0 12 (100%)

1 1
Oozing skin
2 2

3 3

0 15 (100%) 0 12 (100%)

1 1
Symptoms of itchiness
2 2

3 3

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The same group was enrolled in the second test which is the Photocontact
Irritant Potential, wherein a drop of the solution is put on the left forearm
and exposed to UVB light for 5 minutes. The 32 panelists completed the
test.

II. PHOTOCONTACT IRRITANT POTENTIAL GROUP

Table III: Demographic

Characteristics

Gender OLEIA GROUP PLACEBO p value

M 7 10 0.800

F 9 6

Mean Age 40.06 41.31 0.818

Table III showed that there were no significant differences among the
treatment groups for gender and age.

Of the 32 panelists showed in Table IV, none of them developed redness,

welting, oozing, skin rash or developed itchiness. However, one patient
developed post procedure pigmentation that went away spontaneously
without any intervention after 5 days.

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Table IV: Dermal Irritant Score

0-Absent 1-Mild 2-Moderate 3-Severe

OLEIA PLACEBO

0 16 (100%) 0 16 (100%)

1 1
Skin turning red
2 2

3 3

0 16 (100%) 0 16 (100%)

1 1
Welting up
2 2

3 3

0 16 (100%) 0 16 (100%)

1 1
Showing a rash
2 2

3 3

0 16 (100%) 0 16 (100%)

1 1
Oozing skin
2 2

3 3

0 16 (100%) 0 16 (100%)

1 1
Symptoms of itchiness
2 2

3 3

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III. CUMULATIVE IRRITANT GROUP

Eighty four panelists were evaluated for the cumulative irritancy test for 2
weeks. They were monitored after 24 hours, after 1 week and after 2
weeks. During each visit, skin conditions were analyzed using the scoring
pattern. All the data were statistically analyzed using Wilcoxon Signed
Rank Test.

Table V: Demographic

Characteristics

Gender OLEIA GROUP PLACEBO p value

M 25 24 0.800

F 18 17

Mean Age 33.81 36.58 0.915

Table V shows that there were no significant differences in demographic

and baseline characteristics of the panelists.

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Table VI: Skin Turning Red

Dermal Irritant Score

0-Absent 1-Mild 2-Moderate 3-Severe

Day 1 Day 1 Day 7 Day 7 Day 14 Day 14

Score
OLEIA Placebo OLEIA Placebo OLEIA Placebo

0 43/43 41/41 43/43 41/41 43/43 41/41

1 0 0 0 0 0 0

2 0 0 0 0 0 0

3 0 0 0 0 0 0

On Day1, Day7 and Day14, no panelists developed skin redness on both

study groups. No significant differences between the OLEIA and the
placebo groups were noted.

Table VII: Welting Up

Day 1 Day 1 Day 7 Day 7 Day 14 Day 14

Score
OLEIA Placebo OLEIA Placebo OLEIA Placebo

0 43/43 41/41 43/43 41/41 43/43 41/41

1 0 0 0 0 0 0

2 0 0 0 0 0 0

3 0 0 0 0 0 0

On Day1, Day7 and Day14, no panelists developed skin welting up on both

study groups. No significant differences between the OLEIA and the
placebo groups were noted.

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Table VIII: Skin Showing A Rash

Day 1 Day 1 Day 7 Day 7 Day 14 Day 14

Score
OLEIA Placebo OLEIA Placebo OLEIA Placebo

0 43/43 41/41 43/43 41/41 43/43 41/41

1 0 0 0 0 0 0

2 0 0 0 0 0 0

3 0 0 0 0 0 0

On Day1, Day7 and Day14, no panelists developed skin rashes on both

study groups. No significant differences between the OLEIA and the
placebo groups were noted.

Table IX: Oozing Skin

Day 1 Day 1 Day 7 Day 7 Day 14 Day 14

Score
OLEIA Placebo OLEIA Placebo OLEIA Placebo

0 43/43 41/41 43/43 41/41 43/43 41/41

1 0 0 0 0 0 0

2 0 0 0 0 0 0

3 0 0 0 0 0 0

On Day1, Day7 and Day14, no panelists developed oozing skin on both

study groups. No significant differences between the OLEIA and the
placebo groups were noted.

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Table X: Symptoms Of Itchiness

Day 1 Day 1 Day 7 Day 7 Day 14 Day 14

Score
OLEIA Placebo OLEIA Placebo OLEIA Placebo

0 43/43 41/41 43/43 41/41 43/43 41/41

1 0 0 0 0 0 0

2 0 0 0 0 0 0

3 0 0 0 0 0 0

On Day1, Day7 and Day14, no panelists developed symptoms of itchiness

on both study groups. No significant differences between the OLEIA and
the placebo groups were noted.

There was no systemic adverse effect reported except for one case who
developed post UVB light hyperpigmentation but subsequently resolved
after five days of no intervention.

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CONCLUSION

This study demonstrated that OLEIA Oil, a topical pain relief containing
cetylated fatty acids have no skin contact sensitization potentials nor skin
photoallergic potentials.

The results of the 10-week clinical study failed to demonstrate any

cumulative irritancy on all the 84 volunteers.

Both OLEIA and Placebo (0.09 NaCl) showed no statistical difference.

Therefore, the utility of OLEIA Oil is very promising as it is mild, well

tolerated and safe on the skin. Its dermal effect is comparable to a simple
normal saline solution.

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