1
Lola Kelly Smalls, PhD, MBA, Laurie Elstun, MS, Amy Capretta, BS, Paula Hartwig, BS, Michael Thomas, MBA, David Swaile, PhD, P&G Beauty, Cincinnati, Ohio USA INTRODUCTION Prescription (Rx) antiperspirant (AP) products are widely known to induce irritation (erythema, stinging, burning) due to the highly acidic nature of the AP active in vehicles that are not optimized to buffer the skin reactions. This axillary skin irritation limits patient compliance, thus impeding product efficacy. Previously, we shared data from two well-controlled clinical studies that established the prescription strength AP efficacy for an OTC AP compared to a Rx AP 1 . This prescription strength wetness protection OTC AP was formulated to be gentle to the skin by delivering skin-soothing benefits via petrolatum and dimethicone. In these clinical studies we demonstrate the utility of non-contact SIAScopy (Spectrophotometric Intracutaneous Analysis, NCS), an image analysis method that maps skin chromophores (hemoglobin, eumelanin, dermal collagen) 2, 3, 4 , to examine the regional distribution and concentration of hemoglobin in axillary skin treated with a mild OTC AP and an irritating prescription AP. Overall, these data demonstrate that non-contact chromophore mapping via SIAscopy is an effective tool for the assessment of axillary irritation and is consistent with expert clinical irritation assessments, and subject self-perceived data. Additionally, the milder “Soft Solid” OTC AP may increase subject compliance, leading to a more consistent treatment regimen as compared to the more irritating Rx Aluminum Chloride AP. Currently, the image analysis method works well in shaved underarm skin. The method has not been optimized for unshaved skin. In clinical trials, expert irritation assessment is always recommended in conjunction with image analysis methods. Acknowledgements: Image Analysis by Michael Marmor & Kukizo Miyamoto. Evaluate the utility of non-contact SIAscopy for the assessment of axillary irritation via chromophore mapping of hemoglobin with comparison to expert clinical and subject perceived irritation in axillary skin treated with a mild prescription strength wetness protection OTC AP and an irritating prescription AP. OBJECTIVE METHODS Two well-controlled, randomized and blinded paired comparison clinical studies were conducted to evaluate axillary irritation and AP efficacy of a Rx AP containing 6.25% Aluminum Chloride versus an OTC anhydrous, Aluminum Trichlorohydrex GLY AP. The study was conducted for 7-days in healthy females (n=19), with treatments applied 1X/day in the evening. The panelists were evaluated for irritation at each visit. If a panelist had an irritation score of 2 or above (Scale: 0=None to 3=Extreme), product application was discontinued for subject safety and the highest irritation and image scores for that panelist were carried forward for the analysis. Study measurements: Daily high resolution image capture for subsequent non-contact SIAscopy evaluation, AP efficacy (Post-trt 6), daily expert irritation scoring, and daily subject self-reported symptoms. The data were assessed using mixed models or the marginal homogeneity test. RESULTS References 1. Thomas M, Kelly Smalls LR, Leazer TM, Finn E, Elstun LT, Hartwig P, Swaile D, Capretta A. Alternative Topical Treatment to an Aluminum Chloride Antiperspirant that Provides Prescription Strength Efficacy with Significantly Less Irritation. American Academy of Dermatology 65 th Annual Meeting, 2007. 2. Matts, PJ, Fink, B, ,Grammer, K, Burquest, M. Color homogeneity and visual perception of age, health, and attractiveness of female facial skin. J Am Acad Dermatol 2007; 57: 977-84. 3. Matts PJ, Carey J, Cotton SD. Chromophore mapping: a new technique to characterized ageing human skin, invivo, American Academy of Dermatology 63 rd Annual Conference, 2005. 4. Kimball A, Matts, PJ. Characterizing Hyper-pigmented Facial Lesions Using Clinical Evaluation and a New Chromophore- Mapping Technique. American Academy of Dermatology 64 th Annual Meeting, 2006. Chromophore Mapping of Hemoglobin for the Assessment of Axillary Irritation: Comparison of OTC and Prescription Antiperspirants This work was funded by P&G Beauty. CONCLUSIONS 0 1 2 3 4 5 6 7 Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Mean Change from Baseline Hemoglobin Value (higher= more irritation) A (Female OTC Anhydrous "Soft Solid") C (Rx AlCl3 AP) p=0.0337 p=0.0001 p=0.0011 p=0.0003 p<0.0001 Rx Aluminum Chloride AP Anhydrous “Soft Solid” OTC AP Original Image NCS Hemoglobin Map Original Image NCS Hemoglobin Map Female Underarms 0 0.5 1 1.5 2 2.5 3 3.5 4 Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Mean Subject Perceived Irritation Score (higher= more irritation, Scale- 0-10) A (Female OTC Anhydrous "Soft Solid") C (Rx AlCl3 AP) p=0.0148 p=0.0138 p=0.0114 p=0.0104 p=0.0146 Non-contact chromophore mapping of hemoglobin indicated that there was significantly (p<0.05) more irritation for the Rx AP as compared to the OTC AP (Visits 3-7). Additionally, the hemoglobin data were consistent with significant findings (p<0.05) for expert clinical visual irritation scores (Visits 3-7) and subject self-assessments (p<0.05, Visits 3-7). Subject perception data indicated that the irritation from the Rx AP most often felt like stinging and burning. For subject safety, treatment was discontinued at level 2 irritation (Scale:0-3): n=7 on Rx AP and n=0 on Anhydrous OTC AP. Subject Self Perceived Irritation Score by Visit Image Analysis- Change from Baseline Hemoglobin Values 0 10 20 30 40 50 60 70 80 Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 % of Subjects Unfavorable Irritation Comments (higher= more unfavorable) A (Female OTC Anhydrous "Soft Solid") C (Rx AlCl3 AP) p=0.0007 p=0.0038 p=0.0024 p=0.0038 p=0.0079 Subject Self-Perceived Irritation Unfavorable Comments Expert Visual Irritation Assessment by Visit 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Mean Expert Visual Irritation Score (higher= more irritation, Scale- 0-3) A (Female OTC Anhydrous "Soft Solid") C (Rx AlCl3 AP) p=0.0124 p=0.0018 p=0.0003 p=0.0007 p=0.0004 P1000

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Page 1: Academy of Dermatology 65 Academy of Dermatology 63 Annual … 2008 Undera… Irritation.pdf · 2015. 10. 22. · subsequent non-contact SIAscopy evaluation, AP efficacy (Post-trt

Lola

Kel

ly S

mal

ls, P

hD, M

BA, L

aurie

Els

tun,

MS,

Am

y C

apre

tta,

BS,

Pau

la H

artw

ig, B

S, M

icha

el T

hom

as, M

BA, D

avid

Sw

aile

, PhD

, P&

G B

eaut

y, C

inci

nnat

i, O

hio

USA

INTR

OD

UC

TIO

NPr

escr

iptio

n (R

x) a

ntip

ersp

irant

(AP)

pro

duct

s are

wid

ely k

now

n to

indu

ce ir

ritat

ion

(ery

them

a, st

ingi

ng, b

urni

ng)

due

to t

he h

ighl

y ac

idic

natu

re o

fth

e A

P ac

tive

in

vehi

cles

that

are

not

opt

imiz

ed t

o bu

ffer

the

skin

rea

ctio

ns.

This

axill

ary

skin

irr

itatio

n lim

its p

atien

t com

plian

ce, t

hus

impe

ding

pro

duct

effi

cacy

. Pre

viou

sly, w

e sh

ared

da

ta

from

tw

o w

ell-c

ontro

lled

clini

cal

stud

ies

that

es

tabl

ished

th

e pr

escr

iptio

n st

reng

th A

P ef

ficac

y fo

r an

OTC

AP

com

pare

d to

a R

xA

P1 . Th

is pr

escr

iptio

n st

reng

th w

etne

ss p

rote

ctio

n O

TC A

P w

as f

orm

ulat

ed t

o be

gen

tle t

o th

e sk

in b

y de

liver

ing

skin

-soo

thin

g be

nefit

s vi

a pe

trolat

um a

nd d

imet

hico

ne. I

n th

ese

clini

cal

stud

ies

we

dem

onst

rate

th

e ut

ility

of

no

n-co

ntac

t SI

ASc

opy

(Spe

ctro

phot

omet

ricIn

tracu

tane

ous

Ana

lysis,

NCS

), an

imag

e an

alysis

met

hod

that

m

aps s

kin

chro

mop

hore

s(he

mog

lobi

n, e

umela

nin,

der

mal

colla

gen)

2, 3

, 4, t

o ex

amin

e th

e re

gion

al di

strib

utio

n an

d co

ncen

tratio

n of

hem

oglo

bin

in a

xilla

ry s

kin

treat

ed

with

a m

ild O

TC A

P an

d an

irrit

atin

g pr

escr

iptio

n A

P.

Ove

rall,

th

ese

data

de

mon

stra

te

that

no

n-co

ntac

t ch

rom

opho

rem

appi

ng v

ia SI

Asc

opy

is an

effe

ctiv

e to

ol

for

the

asse

ssm

ent

of

axill

ary

irrita

tion

and

is co

nsist

ent

with

exp

ert

clini

cal

irrita

tion

asse

ssm

ents

, an

d su

bjec

t self

-per

ceiv

ed d

ata.

Add

ition

ally,

the

mild

er “

Soft

Solid

”O

TC A

P m

ay in

crea

se su

bjec

t co

mpl

iance

, lea

ding

to a

mor

e co

nsist

ent t

reat

men

t reg

imen

as

com

pare

d to

the

mor

e irr

itatin

g Rx

A

lum

inum

Chl

orid

e A

P.

Curr

ently

, th

e im

age

analy

sis

met

hod

wor

ks

well

in

sh

aved

un

dera

rm s

kin.

Th

e m

etho

d ha

s no

t be

en o

ptim

ized

for

uns

have

d sk

in.

In

clini

cal

trials

, ex

pert

irrita

tion

asse

ssm

ent

is alw

ays

reco

mm

ende

d in

co

njun

ctio

n w

ith

imag

e an

alysis

m

etho

ds.

Ackn

owle

dgem

ents

:Im

age

Ana

lysis

by

Mic

hael

Mar

mor

& K

ukiz

oM

iyam

oto.

Eva

luat

e th

e ut

ility

of n

on-c

onta

ct S

IAsc

opy

for t

he a

sses

smen

t of a

xilla

ry ir

ritat

ion

via

chro

mop

hore

map

ping

of

hem

oglo

bin

with

com

paris

on t

o ex

pert

clini

cal a

nd

subj

ect p

erce

ived

irrit

atio

n in

axi

llary

ski

n tre

ated

with

a m

ild p

resc

riptio

n st

reng

th

wet

ness

pro

tect

ion

OTC

AP

and

an ir

ritat

ing

pres

crip

tion

AP.

OBJ

ECTI

VE

MET

HO

DS

Two

well

-con

trolle

d, r

ando

miz

ed a

nd b

linde

d pa

ired

com

paris

on c

linica

l st

udies

w

ere

cond

ucte

d to

eva

luat

e ax

illar

y irr

itatio

n an

d A

P ef

ficac

y of

a R

x A

P co

ntain

ing

6.25

% A

lum

inum

Chl

orid

e ve

rsus

an

OTC

anh

ydro

us, A

lum

inum

Tric

hlor

ohyd

rex

GLY

AP.

The

stu

dy w

as c

ondu

cted

for

7-d

ays

in h

ealth

y fe

male

s (n

=19

), w

ith

treat

men

ts a

pplie

d 1X

/day

in

the

even

ing.

Th

e pa

nelis

ts w

ere

evalu

ated

for

irr

itatio

n at

eac

h vi

sit.

If a

pan

elist

had

an

irrita

tion

scor

eof

2 o

r ab

ove

(Sca

le:

0=N

one

to 3

=E

xtre

me)

, pro

duct

app

licat

ion

was

disc

ontin

ued

for

subj

ect

safe

ty

and

the

high

est i

rrita

tion

and

imag

e sc

ores

for t

hat p

aneli

st w

ere

carr

ied fo

rwar

d fo

r th

e an

alysis

. St

udy

mea

sure

men

ts:

Dail

y hi

gh

reso

lutio

n im

age

capt

ure

for

subs

eque

nt n

on-c

onta

ct S

IAsc

opy

evalu

atio

n, A

P ef

ficac

y (P

ost-t

rt 6)

, dail

y ex

pert

irrita

tion

scor

ing,

and

dail

y su

bjec

t sel

f-rep

orte

d sy

mpt

oms.

The

data

wer

e as

sess

ed

usin

g m

ixed

mod

els o

r the

mar

gina

l hom

ogen

eity

test

.

RESU

LTS

CO

NC

LUSI

ON

S

Ref

eren

ces

1.Th

omas

M, K

elly

Sm

alls L

R, L

eaze

r TM

, Fin

n E

, Elst

un L

T,

Har

twig

P, S

wail

e D

, Cap

retta

A. A

ltern

ativ

e To

pica

l Tre

atm

ent t

o an

Alu

min

um C

hlor

ide

Ant

iper

spira

nt th

at P

rovi

des P

resc

riptio

n St

reng

th E

ffica

cy w

ith S

igni

fican

tly L

ess I

rrita

tion.

Am

eric

an

Aca

dem

y of

Der

mat

olog

y 65

thA

nnua

l Mee

ting,

200

7.

2.M

atts

, PJ,

Fink

, B, ,

Gra

mm

er, K

, Bur

ques

t, M

. Col

or h

omog

eneit

y an

d vi

sual

perc

eptio

n of

age

, hea

lth, a

nd a

ttrac

tiven

ess o

f fem

ale

faci

al sk

in. J

Am

Aca

dD

erm

atol

2007

; 57:

977

-84.

3.

Mat

ts P

J, Ca

rey

J, Co

tton

SD. C

hrom

opho

rem

appi

ng: a

new

te

chni

que

to c

hara

cter

ized

age

ing

hum

an sk

in, i

nviv

o, A

mer

ican

A

cade

my

of D

erm

atol

ogy

63rd

Ann

ual C

onfe

renc

e, 20

05.

4.K

imba

ll A

, Mat

ts, P

J. Ch

arac

teriz

ing

Hyp

er-p

igm

ente

d Fa

cial

Lesio

ns U

sing

Clin

ical

Eva

luat

ion

and

a N

ew C

hrom

opho

re-

Map

ping

Tec

hniq

ue.

Am

eric

an A

cade

my

of D

erm

atol

ogy

64th

Ann

ual M

eetin

g, 2

006.

Ch

rom

op

ho

reM

app

ing

of

Hem

og

lob

in f

or

the

Ass

essm

ent

of

Axi

llary

Irri

tati

on

: C

om

par

iso

n o

f O

TC a

nd

Pre

scri

pti

on

An

tip

ersp

iran

ts

This

wor

k w

as f

unde

d by

P&

G B

eaut

y.CO

NC

LUSI

ON

S

01234567

Visi

t 1Vi

sit 2

Visi

t 3Vi

sit 4

Visi

t 5Vi

sit 6

Visi

t 7

Mean Change from Baseline Hemoglobin Value (higher= more irritation)

A (F

emal

e O

TC A

nhyd

rous

"S

oft S

olid

")C

(Rx

AlC

l3 A

P)

p=0.

0337

p=0.

0001

p=0.

0011

p=0.

0003

p<0.

0001

Rx

Alu

min

um

Ch

lori

de

AP

An

hyd

rou

s “S

oft

So

lid”

OTC

AP

Ori

gin

al Im

age

NC

S H

emo

glo

bin

Map

Ori

gin

al Im

age

NC

S H

emo

glo

bin

Map

Female Underarms

0

0.51

1.52

2.53

3.54

Vis

it 1

Vis

it 2

Vis

it 3

Vis

it 4

Vis

it 5

Vis

it 6

Vis

it 7

Mean Subject Perceived Irritation Score (higher= more irritation, Scale- 0-10)

A (F

emal

e O

TC A

nhyd

rous

"So

ft S

olid

")C

(Rx

AlC

l3 A

P)

p=0.

0148

p=0.

0138

p=0.

0114

p=0.

0104

p=0.

0146

Non

-con

tact

chr

omop

hore

map

ping

of h

emog

lobi

n in

dica

ted

that

ther

e w

as si

gnifi

cant

ly (p

<0.

05) m

ore

irrita

tion

for t

he

Rx A

P as

com

pare

d to

the

OTC

AP

(Visi

ts 3

-7).

Add

ition

ally,

the

hem

oglo

bin

data

wer

e co

nsist

ent

with

sig

nific

ant

findi

ngs

(p<

0.05

) for

exp

ert c

linica

l visu

al irr

itatio

n sc

ores

(Visi

ts 3

-7) a

nd s

ubjec

t self

-ass

essm

ents

(p<

0.05

, Visi

ts 3

-7).

Subj

ect p

erce

ptio

n da

ta in

dica

ted

that

the

irrita

tion

from

the

Rx A

P m

ost o

ften

felt

like

stin

ging

and

bur

ning

. Fo

r sub

ject

sa

fety

, tre

atm

ent w

as d

iscon

tinue

d at

leve

l 2 ir

ritat

ion

(Sca

le:0-

3): n

=7

on R

x A

P an

d n=

0 on

Anh

ydro

us O

TC A

P.

Subj

ect S

elf P

erce

ived

Irrit

atio

n Sc

ore

by V

isit

Imag

e An

alys

is-C

hang

e fro

m B

asel

ine

Hem

oglo

bin

Valu

es

01020304050607080

Visi

t 1Vi

sit 2

Visi

t 3Vi

sit 4

Visi

t 5Vi

sit 6

Visi

t 7

% of Subjects Unfavorable Irritation Comments(higher= more unfavorable)

A (F

emal

e O

TC A

nhyd

rous

"So

ft So

lid")

C (R

x Al

Cl3

AP)

p=0.

0007

p=0.

0038

p=0.

0024

p=0.

0038

p=0.

0079

Subj

ect S

elf-P

erce

ived

Irrit

atio

n U

nfav

orab

le C

omm

ents

Exp

ert V

isua

l Irr

itatio

n As

sess

men

t by

Visi

t

0

0.2

0.4

0.6

0.81

1.2

1.4

Visi

t 1Vi

sit 2

Visi

t 3Vi

sit 4

Visi

t 5Vi

sit 6

Visi

t 7

Mean Expert Visual Irritation Score(higher= more irritation, Scale- 0-3)

A (F

emal

e O

TC A

nhyd

rous

"So

ft So

lid")

C (R

x Al

Cl3

AP)

p=0.

0124

p=0.

0018

p=0.

0003

p=0.

0007

p=0.

0004

P100

0