PowerPoint Presentation


PRESENTED AT 2021 FALL CLINICAL DERMATOLOGY CONFERENCE, LAS VEGAS, NV, USA, OCTOBER 21–24, 2021

Roflumilast Cream 0.3% Improved the Severity and Impact of Itch in Patients With Chronic Plaque Psoriasis 
in the Phase 3 DERMIS-1 and DERMIS-2 Studies

Efficacy
• Both phase 3 studies met the primary endpoint of IGA Success at Week 8 (Figure 2)

– Significantly greater percentages of roflumilast-treated patients achieved IGA Success with roflumilast than with vehicle
(Figure 2)

• Least squares (LS) mean change from baseline in WI-NRS was significantly greater with roflumilast cream (Figure 3)
• Significantly greater percentages of roflumilast-treated patients achieved ≥4-point reduction in WI-NRS at Week 8 (Figure 4)
• Roflumilast cream reduced the patient-reported severity of itch (Figure 5)
• Roflumilast cream significantly reduced patient-reported burden of itch at all timepoints (Figure 6)
• Roflumilast cream improved patient quality of life as indicated by changes in DLQI (Figure 7)

CONCLUSIONS
• Once-daily treatment with roflumilast cream 0.3% provided significant, consistent, and sustained

improvements in the severity and burden of itch and quality of life in patients with chronic plaque psoriasis
– Onset of action of patient-reported improvements were observed as early as the first timepoint measured

(2 weeks) and improvement continued through Week 8
– Results were reproducible across both phase 3 studies

• Roflumilast cream was associated with low rates of application-site AEs, treatment-related AEs, and
discontinuations due to AEs

• DERMIS-1 and DERMIS-2 support the potential use of investigational roflumilast cream as an effective and
well-tolerated nonsteroidal topical therapy in patients with chronic plaque psoriasis

Melinda J. Gooderham,1 Javier Alonso-Llamazares,2 Jerry Bagel,3 John C. Browning,4 Zoe D. Draelos,5 Kimberly K. Grande,6 Adelaide A. Hebert,7 H. Chih-ho Hong,8 Mark Lebwohl,9 Wei Jing Loo,10 Walter K. Nahm,11 Kim A. Papp, 12 David M. Pariser,13 Jennifer Soung,14 Linda Stein Gold,15 Irina Turchin,16 Amy Feng,17 Patrick Burnett,17
Robert C. Higham,17 David R. Berk17
1Skin Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 2Driven Research LLC, Coral Gables, FL, USA; 3Psoriasis Treatment Center of Central New Jersey, Windsor, NJ, USA; 4Texas Dermatology and Laser Specialists, San Antonio, TX, USA; 5Dermatology Consulting Services, High Point, NC, USA; 6The Skin Wellness Center, P.C., Knoxville, TN, USA; 7UT Health McGovern Medical School, Houston, TX, USA; 
8Probity Medical Research and Department of Dermatology and Skin Science, University of British Columbia, Surrey, BC, Canada; 9Icahn School of Medicine at Mount Sinai, New York, NY, USA; 10DermEffects and Probity Medical Research, London, ON, Canada; 11University of California, San Diego, School of Medicine, La Jolla, CA, USA; 12Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 13Eastern Virginia Medical School and Virginia 
Clinical Research, Inc., Norfolk, VA, USA; 14Southern California Dermatology, Santa Ana, CA, USA; 15Henry Ford Medical Center, Detroit, MI, USA; 16Brunswick Dermatology Center, Fredericton, NB, Canada and Probity Medical Research; 17Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA 

REFERENCES
1. Elewski B, et al. J Eur Acad Dermatol Venereol 2019;33:1465-1476.
2. Globe D, et al. Health Qual Life Outcomes 2009;7:62.
3. Lebwohl MG, et al. N Engl J Med 2020;383:229-239.
4. Lebwohl MG, et al. 2021 European Academy of Dermatology and Venereology Spring Symposium, Sept 29–Oct 2, 2021.

ACKNOWLEDGEMENTS
• This study was supported by Arcutis Biotherapeutics, Inc.
• Thank you to the investigators and their staff for their participation in the trial
• We are grateful to the study participants and their families for their time and commitment
• Writing support was provided by Christina McManus, PhD, Alligent Biopharm Consulting LLC, and funded by Arcutis

Biotherapeutics, Inc.

DISCLOSURES
MJG, JA-L, JB, JCB, ZDD, KKG, AAH, HCH, ML, WJL, WKN, KAP, DMP, JS, LSG, and IT are investigators and/or consultants for 
Arcutis Biotherapeutics, Inc. and received grants/research funding and/or honoraria; AF, PB, RCH, and DRB are employees of 
Arcutis Biotherapeutics, Inc. Additional disclosures provided on request.

INTRODUCTION
• Itch is the most burdensome and frequently reported symptom of psoriasis1,2
• Roflumilast is a selective and highly potent phosphodiesterase-4 inhibitor being investigated as a once-daily, nonsteroidal,

topical treatment for various dermatologic conditions
– Roflumilast cream provided significant and rapid improvement of patients with psoriasis, including improving intertriginous

plaques and reducing itch, in a phase 2b and 2 randomized phase 3, double-blind, vehicle-controlled trials3,4

• Here we report the results of patient-reported outcomes, including itch, from the DERMIS-1 and DERMIS-2 phase 3 trials

METHODS
• DERMIS-1 and DERMIS-2 were identical randomized, multicenter, parallel-group, double-blind, vehicle-controlled studies

(Figure 1)
• Patients eligible for inclusion in the DERMIS-1 and DERMIS-2 studies were ≥2 years old with psoriasis on the face, extremities,

trunk, and/or intertriginous areas involving 2% to 20% of body surface area (BSA), not including the scalp, palms, or soles;
Investigator Global Assessment (IGA) score of at least mild at baseline; and a baseline Psoriasis Area and Severity Index (PASI)
score ≥2

• Patients were randomized 2:1 to receive once-daily (QD) roflumilast cream 0.3% or vehicle cream
• The primary efficacy endpoint for both studies was IGA Success (defined as achievement of clear or almost clear status plus a

≥2-grade improvement from baseline) at Week 8
– Secondary efficacy endpoints included ≥4-point reduction on the Worst Itch-Numeric Rating Scale (WI-NRS Success;

determined in patients ≥12 years with WI-NRS score ≥4 at baseline), change in Psoriasis Symptom Diary Item 1 (severity of
itch), change in Psoriasis Symptom Diary Item 2 (burden of itch), and change in Dermatology Life Quality Index (DLQI)

• The primary endpoint was analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA, and baseline
intertriginous involvement
– Statistical significance was concluded at the 5% significance level (2-sided)
– Missing IGA scores were imputed using multiple imputation

• To control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used
– Upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints

RESULTS
• 439 patients were enrolled in DERMIS-1 and 442 patients were enrolled in DERMIS-2
• Most patients (86.2% to 91.0%) completed the studies (Table 1)

– Few patients discontinued due to adverse events (AEs)
• Baseline disease characteristics were balanced across treatment groups and similar between the 2 studies (Table 2)

Safety
• Safety and tolerability of roflumilast cream were similar to vehicle (Table 3)
• Roflumilast cream demonstrated low rates of application-site AEs, treatment-related AEs, and discontinuations due to AEs

(Table 3)
– Rates were comparable with vehicle

• There were no treatment-related serious AEs
• Application-site reactions were low
• Over 96% of patients in each group had no evidence of irritation at Week 4 or 8 as assessed by the investigators

Table 2. Baseline Disease Characteristics (ITT Population)
DERMIS-1 DERMIS-2

Roflumilast Cream
0.3% 

(n=286)
Vehicle 
(n=153)

Roflumilast Cream
0.3% 

(n=290)
Vehicle 
(n=152)

Psoriasis-affected BSA, mean % (SD) 6.3 (4.38) 7.4 (4.76) 7.1 (4.84) 7.7 (5.05)

IGA score, n (%)

2 (mild) 51 (17.8) 20 (13.1) 50 (17.2) 24 (15.8)

3 (moderate) 206 (72.0) 122 (79.7) 220 (75.9) 118 (77.6)

4 (severe) 29 (10.1) 11 (7.2) 20 (6.9) 10 (6.6)

PASI, mean score (SD) 6.3 (3.15) 6.8 (3.70) 6.5 (3.22) 7.0 (3.52)

WI-NRS, mean score (SD) 5.7 (2.75) 5.7 (2.84) 5.8 (2.61) 6.1 (2.75)

WI-NRS score ≥4, n (%) 218 (76.2) 115 (75.2) 229 (79.0) 116 (76.3)

PSD total score, mean (SD) 72.1 (42.75) 73.4 (41.29) 69.3 (40.66) 77.4 (41.24)

PSD Item 1: severity of itch, mean (SD) 5.5 (2.89) 5.6 (2.88) 5.6 (2.74) 6.0 (2.88)

PSD Item 2: burden of itch, mean (SD) 5.4 (2.97) 5.3 (2.98) 5.4 (2.89) 6.0 (3.02)

DLQI, mean score (SD) 7.4 (5.69) 7.0 (5.04) 6.9 (5.51) 7.8 (5.74)
BSA: body surface area; DLQI: Dermatology Life Quality Index; IGA: Investigator Global Assessment; ITT: intent-to-treat; PASI: Psoriasis Area Severity Index; PSD: Psoriasis Symptoms Diary; 
SD: standard deviation; WI-NRS: Worst Itch-Numeric Rating Scale.

BSA: body surface area; DLQI: Dermatology Life Quality Index; IGA: Investigator Global Assessment; PASI: Psoriasis Area and Severity Index; PSD: Psoriasis Symptom Diary; QD: once daily; 
WI-NRS: Worst Itch-Numeric Rating Scale.

Figure 1. Study Design

ENDPOINTS
Primary
• IGA Success at Week 8
Secondary included
(Weeks 2, 4, 6, and 8)
• WI-NRS
• PSD Item 1

(severity of itch)
• PSD Item 2

(burden of itch)
• DLQI
Safety and tolerability

8 weeks dosing visits: 
Weeks 2, 4, 8

ELIGIBILITY
• Diagnosis of plaque psoriasis

for ≥6 months (3 months for
children)

• Age 2+
• IGA of at least mild severity
• 2–20% BSA
• PASI ≥2

Roflumilast cream 
0.3% QD

Vehicle cream
QD

Ra
nd

om
iz

e

2:1

N=400+

DERMIS-1 N=439
NCT04211363

DERMIS-2 N=442
NCT04211389

Randomized, double-blind, vehicle-controlled, multicenter studies (2 identical, parallel-group, phase 3 studies) 

Table 1. Patient Disposition
DERMIS-1 DERMIS-2

Patients, n (%)

Roflumilast Cream 
0.3% 

(n=286)
Vehicle 
(n=153)

Roflumilast Cream 
0.3% 

(n=290)
Vehicle 
(n=152)

Completed 255 (89.2) 133 (86.9) 264 (91.0) 131 (86.2)
Prematurely discontinued 31 (10.8) 20 (13.1) 26 (9.0) 21 (13.8)

Reason for discontinuation
Withdrawal by patient 11 (3.8) 11 (7.2) 10 (3.4) 11 (7.2)
Physician decision 0 1 (0.7) 0 0
Noncompliance 0 0 0 1 (0.7) 
Protocol violation 1 (0.3) 0 0 0
Lost to follow-up 12 (4.2) 4 (2.6) 15 (5.2) 7 (4.6)
Adverse event 5 (1.7) 2 (1.3) 1 (0.3) 2 (1.3)
Pregnancy 1 (0.3) 0 0 0
Other 1 (0.3) 2 (1.3) 0 0

WI-NRS scale: 0 (no itch) to 10 (worst imaginable itch). Evaluated in the intent-to-treat population of patients; analysis of covariance with treatment, site, baseline IGA, baseline 
intertriginous involvement, and baseline WI-NRS score as independent variables. IGA: Investigator Global Assessment; LS: least squares; SE: standard error; WI-NRS: Worst Itch-
Numeric Rating Scale.

Figure 3. LS Mean Change From Baseline in WI-NRS in DERMIS-1 and DERMIS-2

The primary endpoint was achieved in both DERMIS-1 and DERMIS-2 (Week 8)

Analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA, and baseline intertriginous involvement; 95% CI obtained using the Wilson method; missing scores 
imputed using multiple imputations. Intent-to-treat population. CI: confidence interval; IGA: Investigator Global Assessment.

Figure 2. Percentages of Patients With IGA Success in DERMIS-1 and DERMIS-2

IGA Success = Clear or almost clear plus ≥2-grade improvement from baseline

LS mean change from baseline in WI-NRS: Patient’s assessment of worst itch over the past 24 hours

Improvements in LS mean change from baseline with roflumilast cream 
occurred as early as Week 2 (first timepoint evaluated)

-2.3

-2.9

-3.6 -3.7

-1.0
-1.2

-1.4 -1.4

-5

-4

-3

-2

-1

0
Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

Ch
an

ge
 F

ro
m

 B
as

el
in

e 
(S

E)

Roflumilast 0.3% (n=286) Vehicle (n=153)

***

***

***
Baseline mean (SD) WI-NRS: 

Roflumilast 0.3%: 5.7 (2.75) 
Vehicle: 5.7 (2.84) 

-2.6
-3.0

-3.7
-4.0

-1.2
-0.9

-1.7 -1.7

-5

-4

-3

-2

-1

0
Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

Ch
an

ge
 F

ro
m

 B
as

el
in

e 
(S

E)

Roflumilast 0.3% (n=290) Vehicle (n=152)

***

***
***

Baseline mean (SD) WI-NRS: 
Roflumilast 0.3%: 5.8 (2.61)
Vehicle: 6.1 (2.75) 

***

DERMIS-1 DERMIS-2

***P<0.0001

***

Table 3. Adverse Events

DERMIS-1 DERMIS-2

n (%)

Roflumilast Cream
0.3% 

(n=286)
Vehicle
(n=153)

Roflumilast Cream
0.3% 

(n=290)
Vehicle
(n=152)

Patients with any TEAE 72 (25.2) 36 (23.5) 75 (25.9) 28 (18.4)

Patients with any treatment-related TEAE 7 (2.4) 3 (2.0) 16 (5.5) 8 (5.3)

Patients with any serious AE 2 (0.7) 1 (0.7) 0 1 (0.7)

Patients who discontinued study due to AE 5 (1.7) 2 (1.3) 1 (0.3) 2 (1.3)

Most common TEAE (>2% in any group), preferred term

Hypertensiona 5 (1.7) 6 (3.9) 4 (1.4) 0 

Headache 3 (1.0) 2 (1.3) 11 (3.8) 1 (0.7)

Diarrhea 10 (3.5) 0 8 (2.8) 0

Psoriasis 0 3 (2.0) 1 (0.3) 0

Nasopharyngitis 5 (1.7) 3 (2.0) 1 (0.3) 1 (0.7)
aHypertension includes synonymous terms (eg, blood pressure increased). Data are presented for safety population. AE: adverse event; TEAE: treatment-emergent adverse event.

These two phase 3 studies demonstrate roflumilast cream, an investigational once-daily, nonsteroidal 
topical phosphodiesterase-4 inhibitor, was effective in reducing itch, which decreased disease burden and 
improved quality of life in patients with chronic plaque psoriasis

Evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline IGA, baseline intertriginous involvement, and baseline PSD score as independent 
variables. IGA: Investigator Global Assessment; LS: least squares; PSD: Psoriasis Symptom Diary; SE: standard error; WI-NRS: Worst Itch-Numeric Rating Scale.

Figure 5. LS Mean Percentage Change From Baseline in PSD Item 1 (Severity of Itch)

Evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline IGA, baseline intertriginous involvement, and baseline PSD score as independent 
variables. IGA: Investigator Global Assessment; LS: least squares; PSD: Psoriasis Symptom Diary; SE: standard error; WI-NRS: Worst Itch-Numeric Rating Scale.

Figure 6. LS Mean Percentage Change From Baseline in PSD Item 2 (Bother of Itch)

WI-NRS scale: 0 (no itch) to 10 (worst imaginable itch). Evaluated in a subset of the intent-to-treat population of patients with WI-NRS pruritus score ≥4 at baseline using a Cochran-
Mantel-Haenszel test stratified by site, baseline IGA, and baseline intertriginous involvement; missing scores imputed using multiple imputations; 95% CI obtained using the Wilson 
method. CI: confidence interval; WI-NRS: Worst Itch-Numeric Rating Scale.

Figure 4. Percentages of Patients Achieving ≥4-Point Reduction in WI-NRS

Figure 7. LS Mean Percentage Change From Baseline in DLQI

Evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline IGA, baseline intertriginous involvement, and baseline DLQI score as independent 
variables. DLQI: Dermatology Life Quality Index; IGA: Investigator Global Assessment; LS: least squares; SD: standard deviation; SE: standard error; WI-NRS: Worst Itch-Numeric 
Rating Scale.

0.0

-27.4

-51.2

-65.2

-2.4

-16.8 -12.7

-100
-90
-80
-70
-60
-50
-40
-30
-20
-10

0
10
20
30

Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

%
 C

ha
ng

e 
Fr

om
 B

as
el

in
e 

(S
E)

Roflumilast 0.3% (n=286) Vehicle (n=153)

**

***
Baseline mean (SD) DLQI score: 

Roflumilast 0.3%: 7.4 (5.69) 
Vehicle: 7.0 (5.04)

DERMIS-1

***

LS mean change from baseline in WI-NRS: Patient’s assessment of worst itch over the past 24 hours

LS mean change from baseline in DLQI total scores favored roflumilast over vehicle across both studies

-36.6
-46.8

-69.4

15.0

-2.9

-9.0

-100
-90
-80
-70
-60
-50
-40
-30
-20
-10

0
10
20
30

Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

%
 C

ha
ng

e 
Fr

om
 B

as
el

in
e 

(S
E)

Roflumilast 0.3% (n=290) Vehicle (n=152)

***

***

Baseline mean (SD) DLQI score: 
Roflumilast 0.3%: 6.9 (5.51)
Vehicle: 7.8 (5.74)

***

DERMIS-2

**P<0.01; ***P<0.0001

LS mean percentage change from baseline in PSD Item 2: 
How bothered were you by your psoriasis-related itching over the past 24 hours? 

Significantly greater improvements in burden of itch were observed with roflumilast cream in both studies 

-42.8

-59.7

-70.1 -71.6

-14.9 -12.5 -14.3 -13.8

-100
-90
-80
-70
-60
-50
-40
-30
-20
-10

0
Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

%
 C

ha
ng

e 
Fr

om
 B

as
el

in
e 

(S
E)

Roflumilast 0.3% (n=286) Vehicle (n=153)

***

***

***

-43.9

-63.6 -65.4
-71.8

-15.5
-19.0 -22.6

-28.7

-100
-90
-80
-70
-60
-50
-40
-30
-20
-10

0
Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

%
 C

ha
ng

e 
Fr

om
 B

as
el

in
e 

(S
E)

Roflumilast 0.3% (n=290) Vehicle (n=152)

*** ***
***

***

DERMIS-1 DERMIS-2

***P<0.0001

***

LS mean percentage change from baseline in PSD Item 1: 
How severe was your psoriasis-related itching over the past 24 hours? 

Significantly greater improvements in itch severity were observed with roflumilast cream in both studies

-42.7

-55.2

-67.3
-72.5

-11.1
-18.2 -18.8 -21.5

-100
-90
-80
-70
-60
-50
-40
-30
-20
-10

0
Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

%
 C

ha
ng

e 
Fr

om
 B

as
el

in
e 

(S
E)

Roflumilast 0.3% (n=286) Vehicle (n=153)

***

***

***

-48.9

-60.4
-65.0

-70.5

-18.8 -13.9
-22.6

-26.9

-100
-90
-80
-70
-60
-50
-40
-30
-20
-10

0
Baseline Week 2 Week 4 Week 6 Week 8

LS
 M

ea
n 

%
 C

ha
ng

e 
Fr

om
 B

as
el

in
e 

(S
E)

Roflumilast 0.3% (n=290) Vehicle (n=152)

*** ***
***

***

DERMIS-1 DERMIS-2

***P<0.0001

***

Among patients with baseline WI-NRS score ≥4, more than two-thirds of 
roflumilast-treated patients achieved ≥4-point reduction in WI-NRS 

Proportion of patients who achieved a ≥4-point improvement in WI-NRS from baseline score of ≥4: 
Patient’s assessment of worst itch over the past 24 hours

34.9

50.2
57.8

67.5

22.0 18.0
22.2 26.8

0
10
20
30
40
50
60
70
80
90

100

Week 2 Week 4 Week 6 Week 8

%
 o

f P
at

ie
nt

s 
(9

5%
 C

I)

Roflumilast 0.3% (n=218) Vehicle (n=115)

***
***

***

41.9

56.6
62.0

69.4

21.1 21.9
30.6

35.6

0
10
20
30
40
50
60
70
80
90

100

Week 2 Week 4 Week 6 Week 8

%
 o

f P
at

ie
nt

s 
(9

5%
 C

I)

Roflumilast 0.3% (n=229) Vehicle (n=116)

*** ***
***

**

DERMIS-1 DERMIS-2

**P<0.01; ***P<0.0001

5.9%

20.6%

33.3%

42.4%

2.1% 2.3%
6.1% 6.1%

Week 2 Week 4 Week 6 Week 8

Roflumilast 0.3% (n=286) Vehicle (n=153)

3.3%

19.1%
25.6%

37.5%

2.1%
5.8% 4.7%

6.9%

Week 2 Week 4 Week 6 Week 8

Roflumilast 0.3% (n=290) Vehicle (n=152)

***

*

***
***

***

***

IGA Success 
DERMIS-1

IGA Success 
DERMIS-2

*P<0.05; **P<0.01; ***P<0.0001

**

0

10

20

30

70

80

90

100

40

50

60

%
 o

f  
Pa

ti
en

ts
 (9

5%
 C

I)

0

10

20

30

70

80

90

100

40

50

60

%
 o

f  
Pa

ti
en

ts
 (9

5%
 C

I)


	Roflumilast Cream 0.3% Improved the Severity and Impact of Itch in Patients With Chronic Plaque Psoriasis �in the Phase 3 DERMIS-1 and DERMIS-2 Studies
















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  /GrayImageMinResolutionPolicy /OK
  /DownsampleGrayImages true
  /GrayImageDownsampleType /Bicubic
  /GrayImageResolution 600
  /GrayImageDepth -1
  /GrayImageMinDownsampleDepth 2
  /GrayImageDownsampleThreshold 1.00000
  /EncodeGrayImages false
  /GrayImageFilter /DCTEncode
  /AutoFilterGrayImages true
  /GrayImageAutoFilterStrategy /JPEG
  /GrayACSImageDict <<
    /QFactor 0.15
    /HSamples [1 1 1 1] /VSamples [1 1 1 1]
  >>
  /GrayImageDict <<
    /QFactor 0.15
    /HSamples [1 1 1 1] /VSamples [1 1 1 1]
  >>
  /JPEG2000GrayACSImageDict <<
    /TileWidth 256
    /TileHeight 256
    /Quality 30
  >>
  /JPEG2000GrayImageDict <<
    /TileWidth 256
    /TileHeight 256
    /Quality 30
  >>
  /AntiAliasMonoImages false
  /CropMonoImages false
  /MonoImageMinResolution 1200
  /MonoImageMinResolutionPolicy /OK
  /DownsampleMonoImages true
  /MonoImageDownsampleType /Bicubic
  /MonoImageResolution 600
  /MonoImageDepth -1
  /MonoImageDownsampleThreshold 1.00000
  /EncodeMonoImages false
  /MonoImageFilter /CCITTFaxEncode
  /MonoImageDict <<
    /K -1
  >>
  /AllowPSXObjects false
  /CheckCompliance [
    /None
  ]
  /PDFX1aCheck false
  /PDFX3Check false
  /PDFXCompliantPDFOnly false
  /PDFXNoTrimBoxError true
  /PDFXTrimBoxToMediaBoxOffset [
    0.00000
    0.00000
    0.00000
    0.00000
  ]
  /PDFXSetBleedBoxToMediaBox true
  /PDFXBleedBoxToTrimBoxOffset [
    0.00000
    0.00000
    0.00000
    0.00000
  ]
  /PDFXOutputIntentProfile ()
  /PDFXOutputConditionIdentifier ()
  /PDFXOutputCondition ()
  /PDFXRegistryName ()
  /PDFXTrapped /False

  /CreateJDFFile false
  /Description <<
    /ENU ([Based on 'EPG PRESS RGB'] [Based on 'EPG PRESS RGB'] [Based on '[Press Quality]'] Use these settings to create Adobe PDF documents best suited for high-quality prepress printing.  Created PDF documents can be opened with Acrobat and Adobe Reader 5.0 and later.)
  >>
  /Namespace [
    (Adobe)
    (Common)
    (1.0)
  ]
  /OtherNamespaces [
    <<
      /AsReaderSpreads false
      /CropImagesToFrames true
      /ErrorControl /WarnAndContinue
      /FlattenerIgnoreSpreadOverrides false
      /IncludeGuidesGrids false
      /IncludeNonPrinting false
      /IncludeSlug false
      /Namespace [
        (Adobe)
        (InDesign)
        (4.0)
      ]
      /OmitPlacedBitmaps false
      /OmitPlacedEPS false
      /OmitPlacedPDF false
      /SimulateOverprint /Legacy
    >>
    <<
      /AddBleedMarks false
      /AddColorBars false
      /AddCropMarks true
      /AddPageInfo true
      /AddRegMarks false
      /BleedOffset [
        9
        9
        9
        9
      ]
      /ConvertColors /ConvertToRGB
      /DestinationProfileName (sRGB IEC61966-2.1)
      /DestinationProfileSelector /UseName
      /Downsample16BitImages true
      /FlattenerPreset <<
        /PresetSelector /MediumResolution
      >>
      /FormElements false
      /GenerateStructure true
      /IncludeBookmarks false
      /IncludeHyperlinks false
      /IncludeInteractive false
      /IncludeLayers false
      /IncludeProfiles false
      /MarksOffset 6
      /MarksWeight 0.250000
      /MultimediaHandling /UseObjectSettings
      /Namespace [
        (Adobe)
        (CreativeSuite)
        (2.0)
      ]
      /PDFXOutputIntentProfileSelector /DocumentCMYK
      /PageMarksFile /RomanDefault
      /PreserveEditing true
      /UntaggedCMYKHandling /UseDocumentProfile
      /UntaggedRGBHandling /LeaveUntagged
      /UseDocumentBleed false
    >>
    <<
      /AllowImageBreaks true
      /AllowTableBreaks true
      /ExpandPage false
      /HonorBaseURL true
      /HonorRolloverEffect false
      /IgnoreHTMLPageBreaks false
      /IncludeHeaderFooter false
      /MarginOffset [
        0
        0
        0
        0
      ]
      /MetadataAuthor ()
      /MetadataKeywords ()
      /MetadataSubject ()
      /MetadataTitle ()
      /MetricPageSize [
        0
        0
      ]
      /MetricUnit /inch
      /MobileCompatible 0
      /Namespace [
        (Adobe)
        (GoLive)
        (8.0)
      ]
      /OpenZoomToHTMLFontSize false
      /PageOrientation /Portrait
      /RemoveBackground false
      /ShrinkContent true
      /TreatColorsAs /MainMonitorColors
      /UseEmbeddedProfiles false
      /UseHTMLTitleAsMetadata true
    >>
  ]
>> setdistillerparams
<<
  /HWResolution [2400 2400]
  /PageSize [612.000 792.000]
>> setpagedevice