PowerPoint Presentation


PRESENTED AT THE FALL CLINICAL DERMATOLOGY CONFERENCE FOR PAs & NPs (FCPANP23), JUNE 9–11, 2023, ORLANDO, FL, USA

Figure 8. Percentage of Patients With Investigator-Rated Tolerability Score >0

1.8% 0.6% 1.0% 0.4% 0.0% 0.0%
0

10
20
30
40
50
60
70
80
90

100

Baseline Week 4 Week 12 Week 24 Week 36 Week 52

Pa
ti

en
ts

, %

Overall (N=332)

n=331 n=324 n=304 n=276 n=255 n=238

Figure 5. Median Duration of IGA of Clear or Almost Clear

Duration of IGA 0/1: the time from the first observation of IGA 0/1 to the first subsequent time a patient’s IGA is not IGA 0/1.
Patients who received vehicle in parent study and rolled over into Study 202 with a 0/1 assessment are excluded from this analysis (N=324).
IGA: Investigator Global Assessment.

REFERENCES
1. Dong C, et al. J Pharmacol Exp Ther 2016;358:413–422.

2. Lebwohl MG, et al. N Engl J Med 2020;383:229–239.

3. Stein Gold LS, et al. Poster presented at: Innovations in Dermatology; March 16-20, 2021; Virtual.

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 by Christina McManus, PhD, Alligent Biopharm Consulting LLC, and funded by Arcutis Biotherapeutics, Inc.

DISCLOSURES
ML, LSG, MJG, KAP, LKF, DNA, HCH, LHK, and MZ are investigators and/or consultants for Arcutis Biotherapeutics, Inc. and received 
grants/research funding and/or honoraria; PB, RH, DK, and DB are employees of Arcutis Biotherapeutics, Inc. Additional disclosures 
provided on request.

Mark Lebwohl,1 Linda Stein Gold,2 Melinda J. Gooderham,3 Kim A. Papp,4 Laura K. Ferris,5 David N. Adam,6 H. Chih-ho Hong,7 Leon H. Kircik,8 Matthew Zirwas,9 Patrick Burnett,10 Robert Higham,10
David Krupa,10 David Berk10
1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Henry Ford Medical Center, Detroit, MI, USA; 3SkiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 4Probity Medical Research and K Papp Clinical Research, 
Waterloo, ON, Canada; 5University of Pittsburgh, Department of Dermatology, Pittsburgh, PA, USA; 6CCA Medical Research, Probity Medical Research and Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 7Probity Medical Research and University of 
British Columbia, Department of Dermatology and Skin Science, Surrey, BC, Canada; 8Icahn School of Medicine at Mount Sinai, New York, NY, Indiana Medical Center, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, and Skin Sciences, PLLC, Louisville, KY, USA; 
9Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH, USA; 10Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA

Durability of Efficacy and Safety of Roflumilast Cream 0.3% in Adults With 
Chronic Plaque Psoriasis From a 52-Week, Phase 2 Open-Label Safety Trial

INTRODUCTION
• Roflumilast cream, a phosphodiesterase 4 (PDE4) inhibitor that is more potent than other PDE4 

inhibitors,1 was recently approved as a once-daily, nonsteroidal, topical treatment for psoriasis, 
including intertriginous areas, in patients 12 years of age and older with no limitations on duration 
of use

• In a phase 2b, randomized, double-blind, 12-week trial of 331 adults with chronic plaque psoriasis, 
roflumilast cream once daily was superior to vehicle cream and was well tolerated2

• The durability of response was assessed in a multicenter, open-label, 52-week study conducted to 
evaluate long-term safety of roflumilast 0.3% cream in patients with chronic plaque psoriasis

METHODS
• This multicenter, open-label, single-arm, long-term, phase 2 safety trial was conducted at 30 

centers in the United States and Canada 
• Two cohorts of patients were enrolled: Cohort 1 patients were those who completed the phase 2b 

trial through Week 12, whereas Cohort 2 eligible patients were newly enrolled (treatment-naïve; 
Figure 1)

RESULTS
• Patient demographics and clinical characteristics at baseline were similar across cohorts (Table 1) 
• Of the 249 subjects who completed trial 201 from sites that participated in this open-label trial, 

230 (92.4%) of them enrolled into this study

• A 60.5% mean improvement from baseline in Psoriasis Area Severity Index (PASI) and 60.1% 
mean improvement from baseline in body surface area (BSA) affected were observed at Week 12 
(Figures 6 and 7)
– Results were consistent through Week 52 
– Median BSA at Week 52 was 1.0%

• Safety was consistent with the parent trial (Table 2)
• 94% of adverse events (AEs) were rated mild or moderate in severity 
• 97% of AEs were unrelated or unlikely to be related to treatment as determined by the 

investigator
• ≥97% of patients had no evidence of irritation per investigator local tolerability assessment 

at each visit (Figure 8)

CONCLUSIONS
• In this phase 2 long-term safety study, roflumilast cream 0.3%, a once-daily, nonsteroidal 

topical PDE4 inhibitor, was well-tolerated with a safety profile consistent with the parent 
phase 2b trial (Trial 201) 

– Rates of discontinuations due to AEs and lack of efficacy were low

– No tachyphylaxis occurred and efficacy was consistent over time (IGA Success, IGA 
0/1, and percentage change from baseline in BSA and PASI)

– Of the 185 patients who achieved IGA Clear/Almost Clear during the open-label trial, 
the median durability of IGA of Clear/Almost Clear was 10 months (40.1 weeks)

Figure 4. Percentage of Patients With I-IGA Success Over Time in Cohort 23,a

aCohort 1 not shown because I-IGA added as study amendment and numbers of patients evaluated are very small at each timepoint. 
I-IGA: intertriginous-Investigator Global Assessment; I-IGA Success: I-IGA score of Clear or Almost Clear plus 2-grade improvement from baseline.

Figure 1.  Study Design

aExcludes scalp, palms, soles. 
BSA: body surface area; IGA: Investigator Global Assessment; QD: once daily; PASI: Psoriasis Area Severity Index; SAE: serious adverse event; TEAE: treatment-emergent adverse event.

Figure 3. Percentage of Patients Achieving (A) IGA Success and (B) Clear or Almost Clear

As observed. No imputation of missing values. 
Baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (Cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial (Cohort 1 vehicle group and 
Cohort 2).
IGA: Investigator Global Assessment; IGA Success = IGA score of Clear or Almost Clear plus two-grade improvement from baseline.

42.9

60.0 60.0 56.3
66.7

0
10
20
30
40
50
60
70
80
90

100

Week 4
(n=21)

Week 12
(n=20)

Week 24
(n=20)

Week 36
(n=16)

Week 52
(n=15)

Pa
ti

en
ts

, %

Table 1. Baseline Disease Characteristics
Roflumilast 0.15% and 0.3% 
→ Roflumilast 0.3% (n=164)

Cohort 2 and Vehicle → 
Roflumilast 0.3% (n=168)

Overall (N=332)

BSA, mean % 6.6 6.0 6.3
PASI, mean 7.2 6.3 7.1
IGA score, n (%)

1 (almost clear) 0 (0.0) 8 (4.8) 8 (2.4)
2 (mild) 28 (17.1) 40 (23.8) 68 (20.5)
3 (moderate) 124 (75.6) 110 (65.5) 234 (70.5)
4 (severe) 12 (7.3) 10 (6.0) 22 (6.6)

Intertriginous involvement (I-IGA ≥2)
I-IGA, n (%)

2 (mild) 14 (8.5) 17 (10.1) 31 (9.3)
3 (moderate) 11 (6.7) 18 (10.7) 29 (8.7)
4 (severe) 1 (0.6) 1 (0.6) 2 (0.6)

Baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (Cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial (Cohort 1 vehicle group 
and Cohort 2).
BSA: body surface area; IGA: Investigator Global Assessment; I-IGA: Intertriginous-IGA; PASI: Psoriasis Area Severity Index.

Figure 2. Patient Disposition

aTwo patients withdrew from the study due to “other” reasons, which was COVID-19 disruption.

32.7 36.7 36.0

30.5
35.3

12.9

36.1 29.3

32.0
37.5

0
10
20
30
40
50
60
70
80
90

100

Week 4 Week 12 Week 24 Week 36 Week 52

Pa
ti

en
ts

, %

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)
Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 162 150 136 128 119
Vehicle/Naive → Roflumilast 163 154 140 129 127

A

40.7
45.3

44.9

39.1 42.0

22.6

48.3

39.1

44.3 47.5

0
10
20
30
40
50
60
70
80
90

100

Week 4 Week 12 Week 24 Week 36 Week 52

Pa
ti

en
ts

, %

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)
Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 162 150 136 128 119
Vehicle/Naive → Roflumilast 163 154 140 129 127

B

Roflumilast Cream Phase 2b
(Trial #201; NCT03638258)2

Roflumilast Cream Phase 2 Long-term Safety 
(Trial #202; NCT03764475)

Eligibility
• Diagnosis of 

at least mild 
plaque 
psoriasis

• Age ≥18 years
• 2-20% BSAa

Roflumilast
cream

0.3% QD

Roflumilast 
cream

0.15% QD

Vehicle
QD

Endpoints
Primary: Safety
• Occurrence of 

TEAEs
• Occurrence of 

SAEs
Secondary: Efficacy
• IGA clear or 

almost clear
• Intertriginous-IGA 

clear or almost 
clear

• PASI
• BSA

12 weeks

Ra
nd

om
iz

at
io

n

1:1:1

N=331

Eligibility
• Diagnosis of at least mild 

plaque psoriasis for at least 
6 months

• Age ≥18 years
• 2-25% BSAa

Cohort 1 (Rollovers)
Roflumilast cream 
0.3% QD (n=230)

52 weeks

Cohort 2 (Naïve)
Roflumilast cream 
0.3% QD (n=102)

Completed
Trial #201 
through

12 weeks

Patients could stop applying         
treatment to lesions that cleared
Patients could completely stop 

treatment when PASI and IGA = 0 
following an office visit

Treatment could be resumed when 
patient-observed psoriasis recurred

Roflumilast cream 0.3% 
n=81

Roflumilast cream 0.15% 
n=83

Vehicle cream 
n=66

Completed 
n=244 (73.5%)

Discontinued: 88 (26.5%)
Withdrew: 36 (10.8%) 
Lost to follow-up: 34 (10.2%)
Adverse event: 13 (3.9%)
Lack of efficacy: 3 (0.9%)
Other: 2 (0.6%)a

Cohort 1 Cohort 2

Enrolled
N=332

Roflumilast cream 0.3% 
n=102

Figure 6. Mean PASI Score

Observed data. No imputation of missing values.
PASI assessment was added as an amendment to the trial.
PASI: Psoriasis Area and Severity Index; SD: standard deviation.

Figure 7. Mean Percent BSA Affected 

Observed data. No imputations of missing values.
Baseline is defined as the last observation prior to the first dose of Roflumilast Cream in the ARQ-151-202 study.
BSA: body surface area; SD: standard deviation.

3.37
2.53 2.56

2.57

2.74
3.34

2.50 2.49

2.60

2.37

0
1
2
3
4
5
6
7
8
9

10

Week 4 Week 12 Week 24 Week 36 Week 52

M
ea

n 
PA

SI
 S

co
re

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)

Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 17 65 111 128 119
Vehicle/Naive → Roflumilast 101 122 129 129 127

201 Parent trial baseline mean (SD) PASI:  7.1 (3.3)
Cohort 2 baseline mean (SD) PASI:  6.8 (3.3)

2.6 2.3 2.2 2.2

2.2

3.9

2.6 2.4 2.2

2.2

0
1
2
3
4
5
6
7
8
9

10

Week 4 Week 12 Week 24 Week 36 Week 52

M
ea

n 
BS

A
 A

ff
ec

te
d,

 %

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)
Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 162 150 136 128 119
Vehicle/Naive → Roflumilast 162 154 140 129 127

201 Parent trial baseline mean (SD) BSA:  6.15 (3.9)
Cohort 2 baseline mean (SD) BSA:  6.6 (5.3)

Scale for investigator-rated local tolerability (0–7)
0 = no evidence of irritation
1 = minimal erythema, barely perceptible 
2 = definite erythema, readily visible; minimal edema or minimal 

papular response
3 = erythema and papules
4 = definite edema
5 = erythema, edema and papules
6 = vesicular eruption
7 = strong reaction spreading beyond application site 

~57.1% (n=185) of patients achieved IGA 0/1 during the trial;
patients have a 50% probability of a duration of IGA of Clear or 

Almost Clear of more than 10 months (40.1 weeks)

0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0

Pr
ob

ab
ili

ty
 IG

A
 C

le
ar

or
 A

lm
os

t C
le

ar

4 12 20 28 360 8 16 24 32 44 56 6440 48 6052

Censored

Duration of IGA Clear or Almost Clear (Weeks)

170 139 114 93 69185 166 123 101 82 41 5 063 37 28At risk

Table 2. Summary of AEs (Safety Population) 

TEAE, n (%)

Roflumilast 
0.15% and 0.3% 
→ Roflumilast 
0.3% (n=164)

Cohort 2 and 
Vehicle → 

Roflumilast 0.3% 
(n=168)

Overall
(N=332)

Patients with any TEAE 79 (48.2) 85 (50.6) 164 (49.4)

Patients with any treatment-related TEAE 4 (1.7) 5 (4.9) 9 (2.7)

Patients with any SAE 8 (4.9) 4 (2.4) 12 (3.6)

Any treatment-related SAE 0 (0) 0 (0) 0 (0)

Patients who discontinued study drug due to AE 8 (4.9) 5 (3.0) 13 (3.9)

Most common AEs (>2% overall)

URTI/viral URTI 10 (6.1) 12 (7.1) 22 (6.6)

Nasopharyngitis 6 (3.7) 6 (3.6) 12 (3.6)

Urinary tract infection 5 (3.0) 6 (3.6) 11 (3.3)

Sinusitis 3 (1.8) 5 (3.0) 8 (2.4)
Treatment-emergent adverse event defined as event with an onset on or after the date of the first study drug application in ARQ-151-202 study.
AE: adverse event; SAE: serious adverse event; TEAE: treatment-emergent adverse event; URTI: upper respiratory tract infection.

• 244 (73.5%) completed the 202 trial of the 332 patients enrolled across cohort 1 (n=230) and 
cohort 2 (n=102; Figure 2)

• Percentages of patients achieving Investigator Global Assessment (IGA) Success and an IGA of Clear 
or Almost Clear were consistent over time (Figure 3)

• Among patients with intertriginous area involvement, roflumilast cream provided consistent 
improvement of Intertriginous-Investigator Global Assessment (I-IGA; Figure 4)

• Median duration of IGA of Clear or Almost Clear was 10 months (Figure 5)


	Durability of Efficacy and Safety of Roflumilast Cream 0.3% in Adults With Chronic Plaque Psoriasis From a 52-Week, Phase 2 Open-Label Safety Trial
















<<
  /ASCII85EncodePages false
  /AllowTransparency false
  /AutoPositionEPSFiles true
  /AutoRotatePages /None
  /Binding /Left
  /CalGrayProfile (Gray Gamma 2.2)
  /CalRGBProfile (sRGB IEC61966-2.1)
  /CalCMYKProfile (U.S. Web Coated \050SWOP\051 v2)
  /sRGBProfile (sRGB IEC61966-2.1)
  /CannotEmbedFontPolicy /Warning
  /CompatibilityLevel 1.4
  /CompressObjects /Tags
  /CompressPages false
  /ConvertImagesToIndexed true
  /PassThroughJPEGImages true
  /CreateJobTicket false
  /DefaultRenderingIntent /Default
  /DetectBlends true
  /DetectCurves 0.0000
  /ColorConversionStrategy /UseDeviceIndependentColor
  /DoThumbnails false
  /EmbedAllFonts true
  /EmbedOpenType false
  /ParseICCProfilesInComments true
  /EmbedJobOptions true
  /DSCReportingLevel 0
  /EmitDSCWarnings false
  /EndPage -1
  /ImageMemory 1048576
  /LockDistillerParams false
  /MaxSubsetPct 100
  /Optimize false
  /OPM 1
  /ParseDSCComments true
  /ParseDSCCommentsForDocInfo true
  /PreserveCopyPage true
  /PreserveDICMYKValues true
  /PreserveEPSInfo true
  /PreserveFlatness false
  /PreserveHalftoneInfo false
  /PreserveOPIComments true
  /PreserveOverprintSettings true
  /StartPage 1
  /SubsetFonts true
  /TransferFunctionInfo /Apply
  /UCRandBGInfo /Preserve
  /UsePrologue false
  /ColorSettingsFile ()
  /AlwaysEmbed [ true
    /Museo
    /MuseoSans300
    /MuseoSans700
  ]
  /NeverEmbed [ true
  ]
  /AntiAliasColorImages false
  /CropColorImages false
  /ColorImageMinResolution 300
  /ColorImageMinResolutionPolicy /OK
  /DownsampleColorImages true
  /ColorImageDownsampleType /Bicubic
  /ColorImageResolution 300
  /ColorImageDepth -1
  /ColorImageMinDownsampleDepth 1
  /ColorImageDownsampleThreshold 1.00000
  /EncodeColorImages false
  /ColorImageFilter /DCTEncode
  /AutoFilterColorImages true
  /ColorImageAutoFilterStrategy /JPEG
  /ColorACSImageDict <<
    /QFactor 0.15
    /HSamples [1 1 1 1] /VSamples [1 1 1 1]
  >>
  /ColorImageDict <<
    /QFactor 0.15
    /HSamples [1 1 1 1] /VSamples [1 1 1 1]
  >>
  /JPEG2000ColorACSImageDict <<
    /TileWidth 256
    /TileHeight 256
    /Quality 30
  >>
  /JPEG2000ColorImageDict <<
    /TileWidth 256
    /TileHeight 256
    /Quality 30
  >>
  /AntiAliasGrayImages false
  /CropGrayImages false
  /GrayImageMinResolution 300
  /GrayImageMinResolutionPolicy /OK
  /DownsampleGrayImages true
  /GrayImageDownsampleType /Bicubic
  /GrayImageResolution 300
  /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 450
  /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