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Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00773734
First received: October 14, 2008
Last updated: November 6, 2014
Last verified: November 2014
  Purpose

The purpose of this study was to test if the drug apremilast was safe, if it helped improve psoriasis, and how well the participants tolerated it.


Condition Intervention Phase
Psoriasis
Plaque-type Psoriasis
Drug: Apremilast 10mg
Drug: Apremilast 20mg
Drug: Apremilast 30 mg
Drug: Placebo
Drug: Apremilast 30mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Core Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in Psoriasis Area and Severity Index (PASI) at Week 16 [ Time Frame: Week 0 and Week 16 ] [ Designated as safety issue: No ]
    PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).


Secondary Outcome Measures:
  • Core Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in PASI Score at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy.The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head,trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Core Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in PASI Score at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]
    PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Core Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Core Study: Percentage of Participants Who Achieved a 90% Improvement (Response) From Baseline in the PASI Score at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]
    PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Core Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy..The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Core Study: Percentage of Participants Who Achieved a 100% Improvement (Response) in the PASI Score at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]
    A participant was classified as having achieved a PASI-100 response if the PASI score was reduced by at least 100% from baseline. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Core Study: Percentage of Participants Who Achieved a 100% Improvement (Response) in the PASI Score at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    A participant was classified as having achieved a PASI-100 response if the PASI score was reduced by at least 100% from baseline. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Core Study: Time to Achieve a PASI-50 Response During the Placebo Controlled Phase [ Time Frame: Week 0 to16 ] [ Designated as safety issue: No ]
    For PASI-50 responders in the placebo-controlled period weeks 0-16, time to achieve PASI-50 was defined as the time interval, inclusive between the date of randomization (day 1) and the date of the first assessment where PASI-50 was achieved.

  • Core Study: Time to Achieve a PASI-75 Response During the Placebo Controlled Phase [ Time Frame: Weeks 0 to16 ] [ Designated as safety issue: No ]
    For PASI-75 responders in the placebo-controlled period Weeks 0-16, time to achieve PASI-75 was defined as the time interval, inclusive between the date of randomization (day 1) and the date of the first assessment where PASI-75 is achieved.

  • Core Study: Time to Achieve a PASI-90 Response During the Placebo Controlled Phase [ Time Frame: Weeks 0-16 ] [ Designated as safety issue: No ]
    For PASI-90 responders in the placebo-controlled period weeks 0-16, time to achieve PASI-90 was the time interval, inclusive, between the date of randomization (day 1) and the date of the first assessment where PASI-90 was achieved.

  • Core Study: Time to Achieve a PASI-100 Response During the Placebo Controlled Phase [ Time Frame: Weeks 0 to 16 ] [ Designated as safety issue: No ]
    For PASI-100 responders in the placebo-controlled period weeks 0-16, time to achieve PASI-100 was the time interval, inclusive, between the date of randomization (day 1) and the date of the first assessment where PASI-90 was achieved.

  • Core Study: Percent Change From Baseline in PASI Score at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]
    The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score.

  • Core Study: Percent Change From Baseline in PASI Score at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score

  • Core Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]

    Physician Global Assessment (sPGA) was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3).


  • Core Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    Physician Global Assessment (sPGA) was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3).

  • Core Study: Percent Change From Baseline in the Percent of Affected Body Surface Area (BSA) During the Placebo Controlled Phase [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]
    The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or "handprint"), which equates to approximately 1% of total BSA.

  • Core Study: Percent Change From Baseline in the Percent of Affected Body Surface Area (BSA) During the Active Treatment Phase at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or "handprint"), which equates to approximately 1% of total BSA.

  • Core Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]
    The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis.

  • Core Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis.

  • Core Study: Change From Baseline in the Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2; Mental Component Summary Score at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Core Study: Change From Baseline in the Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2; Physical Component Summary Score at Week 16 [ Time Frame: Week 0 to week 16 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Core Study: Change From Baseline in the Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2; Mental Component Summary Score at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Core Study: Change From Baseline in the Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2 Physical Component Summary Score at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Core Study: Area Under the Plasma Concentration-time Curve (AUC0-8) [ Time Frame: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast ] [ Designated as safety issue: No ]
    Area under the concentration versus time curve from time 0 (pre-dose) to 8 hours, calculated using the linear trapezoid rule.

  • Core Study: Area Under the Plasma Concentration-time Curve (AUC0-8) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Area under the concentration versus time curve from time 0 (pre-dose) to 8 hours, calculate using the linear trapezoid rule.

  • Core Study: Peak; (Maximum) Plasma Concentration (Cmax) of Apremilast [ Time Frame: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast ] [ Designated as safety issue: No ]
    The maximum observed plasma concentration of apremilast observed at Week 14 (steady-state Cmax)

  • Core Study: Peak; (Maximum) Plasma Concentration (Cmax) of Apremilast [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The maximum observed plasma concentration of apremilast observed at Week 24 (steady-state Cmax)

  • Core Study: Time to Maximum Plasma Concentration of Drug (Tmax) [ Time Frame: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast ] [ Designated as safety issue: No ]
    Time to achieve maximum plasma concentration (Cmax) observed at Week 14 (Time to achieve steady-state Tmax)

  • Core Study: Time to Maximum Plasma Concentration of Drug (Tmax) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Time to achieve maximum plasma concentration (tmax) observed at Week 24 (Time to achieve steady-state Tmax)

  • Extension Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 52. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 32 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]
    PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 40 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 32 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]
    PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 52 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 32 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]
    PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 40 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 52 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 100% Improvement (Response) in the PASI Score at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    A participant was classified as having achieved a PASI-100 response if the PASI score was reduced by at least 100% from baseline. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 100% Improvement (Response) in the PASI Score at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]
    A participant was classified as having achieved a PASI-100 response if the PASI score was reduced by at least 100% from baseline. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Percentage of Participants Who Achieved a 100% Improvement (Response) in the PASI Score at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    A participant was classified as having achieved a PASI-100 response if the PASI score was reduced by at least 100% from baseline. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

  • Extension Study: Time to Achieve PASI-75 During the Extension Study [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    For PASI-75 responders in the extension study, time to achieve PASI-75 was defined as the time interval, inclusive between the date of randomization (Day 1) and the date of the first assessment where PASI-75 was achieved.

  • Extension Study: Time to Achieve PASI-50 During the Extension Study [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    For PASI-50 responders in the extension study, time to achieve PASI-50 was defined as the time interval, inclusive between the date of randomization (Day 1) and the date of the first assessment where PASI-50 was achieved.

  • Extension Study: Time to Achieve PASI-90 During the Extension Study [ Time Frame: Week 0 to Extension study ] [ Designated as safety issue: No ]
    For PASI-90 responders in the extension study, time to achieve PASI-90 was defined as the time interval, inclusive between the date of randomization (Day 1) and the date of the first assessment where PASI-90 was achieved.

  • Extension Study: Time to Achieve PASI-100 During the Extension Study [ Time Frame: Week 0 to Extension Study ] [ Designated as safety issue: No ]
    For PASI-100 responders in the extension study, time to achieve PASI-100 was defined as the time interval, inclusive between the date of randomization (Day 1) and the date of the first assessment where PASI-100 was achieved.

  • Extension Study: Percent Change in PASI Score at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score

  • Extension Study: Percent Change in PASI Score at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score

  • Extension Study: Percent Change in PASI Score at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score

  • Extension Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]

    Physician Global Assessment (sPGA) was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the subject and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3).


  • Extension Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]

    Physician Global Assessment (sPGA) was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the subject and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3).


  • Extension Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]

    Physician Global Assessment (sPGA) was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the subject and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3).


  • Extension Study: Percent Change From Baseline in the Affected BSA at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or "handprint"), which equates to approximately 1% of total BSA.

  • Extension Study: Percent Change From Baseline in the Affected BSA at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]
    The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or "handprint"), which equates to approximately 1% of total BSA.

  • Extension Study: Percent Change From Baseline in the Affected BSA at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or "handprint"), which equates to approximately 1% of total BSA.

  • Extension Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis.

  • Extension Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]
    The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis.

  • Extension Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis.

  • Extension Study: Change From Baseline in the Medical Outcome Study Short Form,SF-36, Version 2; Mental Component Summary Score at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Extension Study: Change From Baseline in the Medical Outcome Study Short Form,SF-36, Version 2; Physical Component Summary Score (PCS) at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Extension Study: Change From Baseline in the Medical Outcome Study Short Form,SF-36, Version 2; Mental Component Summary Score at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Extension Study: Change From Baseline in Medical Outcome Study Short Form,SF-36, Version 2; Physical Component Summary Score at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Extension Study: Change From Baseline in the Medical Outcome Study Short Form,SF-36, Version 2; Mental Component Summary Score at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Extension Study: Change From Baseline in the Medical Outcome Study Short Form,SF-36, Version 2; Physical Component Summary Score at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]

    The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value..


  • Extension Study: Dose-response Relationship Using the Percent Reduction of PASI Scores at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
    Dose response relationship using percent reduction in PASI scores across dose groups at Week 52 compared to Week 0

  • Extension Study: Time to Loss of Response During the Treatment Phase of the Extension Study. [ Time Frame: Week 0 to 52 ] [ Designated as safety issue: No ]
    Time to 50% loss of the maximal improvement (achieved in either the core study or the extension study) during the treatment phase of the extension study, in participants who achieved ≥ PASI-50 in either the core study or during the treatment phase of the extension study

  • Time to Loss of 50% of the PASI Response During the Observational Follow-up Phase Relative to the End of Treatment (Participants Who Had at Least a PASI-50 Response at the End of Treatment Phase) [ Time Frame: Up to 4 weeks after the last dose ] [ Designated as safety issue: No ]
    Time to loss of response was modified to be 50% loss in the PASI response observed at the end of treatment for participants who achieved at least a PASI-50 at the end of treatment. This definition was changed since participants may have already lost their maximal PASI response prior to enrollment into the Observation Follow-up Phase. Included all participants that enrolled into the observational follow-up phase after the treatment phase.

  • Number of Participants With Treatment Emergent Adverse Events (TEAE) in the Placebo Controlled Phase [ Time Frame: Week 0 to Week 16; up to data cut off of 21 July 2011 ] [ Designated as safety issue: Yes ]
    An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.

  • Number of Participants With Treatment Emergent Adverse Events (TEAE) in the Apremilast Exposure Period [ Time Frame: Week 0-88; up to data cut off of 21 July 2011 ] [ Designated as safety issue: Yes ]
    An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.


Other Outcome Measures:
  • Core Study: Percentage of Participants With a Static Physician Global Assessment (sPGA) Greater Than 2 at Baseline Who Achieved a Score of 0 or 1 at Week 16 [ Time Frame: Week 0 to Week 16 ] [ Designated as safety issue: No ]

    The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease


  • Core Study: Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of 0 or 1 at Week 24 [ Time Frame: Week 0 and Week 24 ] [ Designated as safety issue: No ]

    The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease


  • Extension Study: Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of 0 or 1 at Week 32 [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]

    The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease.


  • Extension Study: Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of 0 or 1 at Week 40 [ Time Frame: Week 0 to Week 40 ] [ Designated as safety issue: No ]

    The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less disease.


  • Extension Study: Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of 0 or 1 at Week 52 [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]

    The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling).

    The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease.



Enrollment: 352
Study Start Date: September 2008
Study Completion Date: October 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast 10mg
Apremilast 10 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 10 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase
Drug: Apremilast 10mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Experimental: Apremilast 20mg
Apremilast 20 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 20 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase
Drug: Apremilast 20mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Experimental: Apremilast 30 mg
Apremilast 30 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 30 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase
Drug: Apremilast 30 mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Placebo Comparator: Placebo
Oral Placebo tablets administered twice daily (BID) for 16 weeks during the placebo-controlled phase.
Drug: Placebo
Experimental: Placebo/Apremilast 20 mg
Participants initially randomized to receive placebo twice daily during the 16 week placebo controlled phase were re-randomized to 20 mg apremilast BID during the 8 week active treatment phase
Drug: Apremilast 20mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Experimental: Placebo/Apremilast 30mg
Participants initially randomized to receive placebo twice daily during the 16 week placebo controlled phase were re-randomized to 30 mg apremilast BID during the 8 week active treatment phase
Drug: Apremilast 30mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla

Detailed Description:

This study fully explored the extent of treatment benefit achieved with doses of apremilast up to 30 mg by mouth (PO) twice daily (BID) with treatment duration for up to 6 months. In addition, it was important to determine the minimally effective dose for apremilast and more fully elucidate the dose response curve in this patient population. The results from this study helped guide the selection of the dose in the phase 3 trials.

Participants meeting eligibility criteria at the Baseline Visit (Week 0) were centrally randomized with the use of a permuted-block randomization list, with equal allocation to each of the four treatment arms: 10 mg, 20 mg or 30 mg PO BID of apremilast or placebo. In an effort to mitigate the dose-dependent adverse effects of apremilast (e.g., headache or gastrointestinal disturbances), participants had their dose titrated over a 7-day period (Days 1 through7). Participants received 10 mg PO BID of apremilast or identically-appearing placebo during Days 1 to 2. Participants randomized to the 10 mg BID dose continued taking this dose throughout the treatment phase of the study. Those participants randomized to the 20 mg BID dose were dose titrated to 20 mg PO BID of apremilast or identically-appearing placebo during Days 3 to 4 of dosing. Participants randomized to the 20 mg BID dose continued taking this dose throughout the treatment phase of the study. Those participants randomized to the 30 mg BID dose were dose titrated to 30 mg PO BID of apremilast or identically-appearing placebo during Days 5 to 7 and continued taking this dose throughout the treatment phase of the study. At Week 16, all participants originally randomized to the placebo arm were re-randomized to 20 mg BID or 30 mg BID of apremilast. All participants (i.e., those that were continuing their Apremilast dosing regimen, as well as those that were switched from placebo to apremilast) received drug at Week 16 in a treatment arm in a blinded fashion. In addition, participants who transitioned from placebo to active medication at Week 16 completed a dose titration schedule to help mitigate any potential GI side effects that may have jeopardized the blinding of the treatment arms.

At Week 24 (end of core study and beginning of an extension study), participants were given the option to enroll into an extension study (PSOR-005E NCT00953875) and continue on the same apremilast dosage they had received at the end of the core study, during Weeks 24-52, a total of 28 weeks. Participants who elected not to enter into the treatment extension study, completed a 4-week observational follow-up phase of the core study. At Week 52 (end of extension study and beginning of a long-term extension study), participants were given the option to enroll into a long term extension study (PSOR-005LTE NCT01130116), for 4 additional years. Participants who were treated with apremilast 10 mg BID in the extension study were randomly assigned and dose titrated to either apremilast 20 mg BID or 30 mg BID. Participants who were dosed with 20mg or 30 mg BID in the extension study continued to receive the same dose in the long-term extension study. The long-term extension study is anticipated to complete in May 2016.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • ≥18 years of age at the time of signing the informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Diagnosis of chronic, stable plaque psoriasis at least 6 months prior to screening as defined by:

    1. PASI (Psoriasis Area and Severity Index) score ≥ 12
    2. Body Surface Area (BSA) ≥ 10%
  • Candidate for photo/systemic therapy
  • In good health as judged by the investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), serum chemistry, hematology, immunology, and urinalysis
  • Meet all laboratory criteria as defined per protocol
  • Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the following adequate forms of contraception methods. A FCBP must agree to have pregnancy tests every 4 weeks while on study medication
  • Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for 84 days after taking the last dose of study medication

Exclusion Criteria:

  • History of clinically significant disease (as determined by the investigator)
  • Pregnant or breastfeeding
  • History of active mycobacterial infection within 3 years
  • History of Human Immunodeficiency Virus (HIV) infection
  • Congenital and acquired immunodeficiencies
  • Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening
  • Antibodies to Hepatitis C at screening
  • Malignancy or history of malignancy except for treated [i.e., cured] basal-cell skin carcinomas
  • Any condition, including the presence of laboratory abnormalities, that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Psoriasis flare within 4 weeks of screening
  • Topical therapy within 2 weeks of randomization
  • Systemic therapy for psoriasis within 4 weeks of randomization
  • Use of phototherapy within 4 weeks of randomization [(i.e., Ultraviolet (UVB), Psoralens and long-wave ultraviolet radiation (PUVA)]
  • Adalimumab, etanercept, efalizumab or infliximab within 12 weeks of randomization
  • Alefacept within 24 weeks of randomization
  • Investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer)
  • Prolonged sun exposure or use of tanning booths or other ultraviolet light sources
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773734

  Show 35 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Irina Khanskaya, MD Celgene Corporation
  More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00773734     History of Changes
Obsolete Identifiers: NCT00953875, NCT01130116
Other Study ID Numbers: CC-10004-PSOR-005
Study First Received: October 14, 2008
Results First Received: October 22, 2014
Last Updated: November 6, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Celgene Corporation:
moderate-to-severe plaque-type psoriasis

Additional relevant MeSH terms:
Psoriasis
Skin Diseases
Skin Diseases, Papulosquamous
Apremilast
Thalidomide
Analgesics
Analgesics, Non-Narcotic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antirheumatic Agents
Central Nervous System Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014