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

Amgen352 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

352

Conditions

Psoriasis Plaque-type Psoriasis

Interventions

Apremilast 10mgDRUG

Apremilast 20mgDRUG

Apremilast 30 mgDRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (35)

Outcomes

Primary Outcomes

Core Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in Psoriasis Area and Severity Index (PASI) at Week 16

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).

Time frame: Week 0 and Week 16

Secondary Outcomes

Core Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in PASI Score at Week 24

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).

Time frame: Week 0 to Week 24

Core Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in PASI Score at Week 16

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).

Data from ClinicalTrials.gov

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Associates In Research Inc

Fresno, California, United States

Dermatology Associates

Los Angeles, California, United States

Stanford University School of Medicine

Redwood City, California, United States

Atlantic Skin & Cosmetic Surgery Group, PC

Wilmington, Delaware, United States

Renstar Medical Research

Ocala, Florida, United States

Atlanta Dermatology, Vein & Research Center

Alpharetta, Georgia, United States

NorthShore University HealthSystem

Skokie, Illinois, United States

Dawes/Fretzin Dermatology Group Inc

Indianapolis, Indiana, United States

Dermatology & Advanced Aesthetics

Lake Charles, Louisiana, United States

Minnesota Clinical Study Center

Fridley, Minnesota, United States

...and 25 more locations

Time frame: Week 0 to Week 16

Core Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 24

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).

Time frame: Week 0 to Week 24

Core Study: Percentage of Participants Who Achieved a 90% Improvement (Response) From Baseline in the PASI Score at Week 16

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).

Time frame: Week 0 to Week 16

Core Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 24

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).

Time frame: Week 0 to Week 24

Core Study: Percentage of Participants Who Achieved a 100% Improvement (Response) in the PASI Score at Week 16

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).

Time frame: Week 0 to Week 16

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

Core Study: Time to Achieve a PASI-100 Response During the Placebo Controlled Phase

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.

Time frame: Weeks 0 to 16

Core Study: Percent Change From Baseline in PASI Score at Week 16

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.

Time frame: Week 0 to Week 16

Core Study: Percent Change From Baseline in PASI Score at Week 24

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

Time frame: Week 0 to Week 24

Core Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 16

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).

Time frame: Week 0 to Week 16

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

Core Study: Percent Change From Baseline in the Percent of Affected Body Surface Area (BSA) During the Placebo Controlled Phase

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.

Time frame: Week 0 to Week 16

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

Core Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16

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.

Time frame: Week 0 to Week 16

Core Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 24

Time frame: Week 0 to Week 24

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

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.

Time frame: Week 0 to Week 16

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

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

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

Core Study: Area Under the Plasma Concentration-time Curve (AUC0-8)

Area under the concentration versus time curve from time 0 (pre-dose) to 8 hours, calculated using the linear trapezoid rule.

Time frame: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast

Core Study: Area Under the Plasma Concentration-time Curve (AUC0-8)

Area under the concentration versus time curve from time 0 (pre-dose) to 8 hours, calculate using the linear trapezoid rule.

Time frame: Week 24

Core Study: Peak; (Maximum) Plasma Concentration (Cmax) of Apremilast

The maximum observed plasma concentration of apremilast observed at Week 14 (steady-state Cmax)

Time frame: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast

Core Study: Peak; (Maximum) Plasma Concentration (Cmax) of Apremilast

The maximum observed plasma concentration of apremilast observed at Week 24 (steady-state Cmax)

Time frame: Week 24

Core Study: Time to Maximum Plasma Concentration of Drug (Tmax)

Time to achieve maximum plasma concentration (Cmax) observed at Week 14 (Time to achieve steady-state Tmax)

Time frame: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast

Core Study: Time to Maximum Plasma Concentration of Drug (Tmax)

Time to achieve maximum plasma concentration (tmax) observed at Week 24 (Time to achieve steady-state Tmax)

Time frame: Week 24

Extension Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at Week 52

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).

Time frame: Week 0 to Week 52

Extension Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at Week 32

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).

Time frame: Week 0 to Week 32

Extension Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at Week 40

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).

Time frame: Week 0 to Week 40

Extension Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 32

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).

Time frame: Week 0 to Week 32

Extension Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 40

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).

Time frame: Week 0 to Week 40

Extension Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 52

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).

Time frame: Week 0 to Week 52

Extension Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 32

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).

Time frame: Week 0 to Week 32

Extension Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 40

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).

Time frame: Week 0 to Week 40

Extension Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 52

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).

Time frame: Week 0 to Week 52

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

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

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

Extension Study: Time to Achieve PASI-75 During the Extension Study

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.

Time frame: Week 0 to Week 52

Extension Study: Time to Achieve PASI-50 During the Extension Study

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.

Time frame: Week 0 to Week 52

Extension Study: Time to Achieve PASI-90 During the Extension Study

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.

Time frame: Week 0 to Extension study

Extension Study: Time to Achieve PASI-100 During the Extension Study

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.

Time frame: Week 0 to Extension Study

Extension Study: Percent Change in PASI Score at Week 32

Time frame: Week 0 to Week 32

Extension Study: Percent Change in PASI Score at Week 40

Time frame: Week 0 to Week 40

Extension Study: Percent Change in PASI Score at Week 52

Time frame: Week 0 to Week 52

Extension Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 32

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).

Time frame: Week 0 to Week 32

Extension Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 40

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).

Time frame: Week 0 to Week 40

Extension Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Week 52

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).

Time frame: Week 0 to Week 52

Extension Study: Percent Change From Baseline in the Affected BSA at Week 32

Time frame: Week 0 to Week 32

Extension Study: Percent Change From Baseline in the Affected BSA at Week 40

Time frame: Week 0 to Week 40

Extension Study: Percent Change From Baseline in the Affected BSA at Week 52

Time frame: Week 0 to Week 52

Extension Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 32

Time frame: Week 0 to Week 32

Extension Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 40

Time frame: Week 0 to Week 40

Extension Study: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 52

Time frame: Week 0 to Week 52

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

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

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

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

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

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

Extension Study: Dose-response Relationship Using the Percent Reduction of PASI Scores at Week 52

Dose response relationship using percent reduction in PASI scores across dose groups at Week 52 compared to Week 0

Time frame: Week 0 to Week 52

Extension Study: Time to Loss of Response During the Treatment Phase of the Extension Study.

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 frame: Week 0 to 52

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 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.

Time frame: Up to 4 weeks after the last dose

Number of Participants With Treatment Emergent Adverse Events (TEAE) in the Placebo Controlled Phase

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.

Time frame: Week 0 to Week 16; up to data cut off of 21 July 2011

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

Core Study: Time to Achieve a PASI-50 Response During the Placebo Controlled Phase

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.

Time frame: Week 0 to 16

Core Study: Time to Achieve a PASI-75 Response During the Placebo Controlled Phase

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.

Time frame: Weeks 0 to 16

Core Study: Time to Achieve a PASI-90 Response During the Placebo Controlled Phase

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.

Time frame: Weeks 0 to 16

Number of Participants With Treatment Emergent Adverse Events (TEAE) in the Apremilast Exposure Period

Time frame: Week 0 to 6 years of study treatment; maximum duration of exposure was 314.6 weeks

LTE Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at 18 Months

PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score. 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).

Time frame: Week 0 to Month 18

LTE Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at 2 Years

PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI. 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).

Time frame: Week 0 to Month 24

LTE Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in the PASI Score at 4 Years

Time frame: Week 0 to Month 48

LTE Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at 18 Months

PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score. 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).

Time frame: Week 0 to Month 18

LTE Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at 2 Years

Time frame: Week 0 to Month 24

LTE Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at 4 Years

Time frame: Week 0 to Month 48

LTE Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at 18 Months

PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 76 of the long-term 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).

Time frame: Week 0 to Month 18

LTE Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at 2 Years

PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 100 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).

Time frame: Week 0 to Month 24

LTE Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at 3 Years

PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 148 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).

Time frame: Week 0 to Month 36

LTE Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at 4 Years

PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 196 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).

Time frame: Week 0 to Month 48

LTE Study: Percentage of Participants Who Achieved a 100% Improvement (Response) in the PASI Score at 18 Months, 2 Years, 3 Years and 4 Years

PASI-100 response is the percentage of participants who achieved at a 100% reduction (improvement) from baseline in PASI score of the long-term 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).

Time frame: Week 0 to Month 48

LTE Study: Percent Change From Baseline in PASI Score at 18 Months

Time frame: Week 0 to Month 18

LTE Study: Percent Change From Baseline in PASI Score at 2 Years

Time frame: Week 0 to Month 24

LTE Study: Percent Change From Baseline in PASI Score at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Percent Change From Baseline in PASI Score at 4 Years

Time frame: Week 0 to Month 48

Core Study: Shift Change (1 or More Points on a 0 to 5 Point Scale) in Static Physician Global Assessment (sPGA) at Month 18, and Years 2, 3 and 4

Time frame: Week 0 to Week 196

LTE Study: Percent Change From Baseline in the Percent of the Affected Body Surface Area (BSA) at 18 Months

Time frame: Week 0 to Month 18

LTE Study: Percent Change From Baseline in the Percent of the Affected Body Surface Area (BSA) at 2 Years

Time frame: Week 0 to Month 24

LTE Study: Percent Change From Baseline in the Percent of the Affected Body Surface Area (BSA) at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Percent Change From Baseline in the Percent of the Affected Body Surface Area (BSA) at 4 Years

Time frame: Week 0 to Month 48

LTE Study: Median Percent Change From Baseline in the Affected Body Surface Area (BSA) at 18 Months

Time frame: Week 0 to Month 18

LTE Study: Median Percent Change From Baseline in the Affected Body Surface Area (BSA) at 2 Years

Time frame: Week 0 to Month 24

LTE Study: Median Percent Change From Baseline in the Affected Body Surface Area (BSA) at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Median Percent Change From Baseline in the Affected Body Surface Area (BSA) at 4 Years

Time frame: Week 0 to Month 48

LTE Study: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at 18 Months

Time frame: Week 0 to Month 18

LTE Study: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at 2 Years

Time frame: Week 0 to Month 24

LTE Study: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at 4 Years

Time frame: Week 0 to Month 48

LTE Study: Change From Baseline in the Medical Outcome Study Short Form, SF-36, Version 2; Mental Component Summary Score at 18 Months

Time frame: Week 0 to Month 18

LTE Study: Change From Baseline in the Medical Outcome Study Short Form, SF-36, Version 2; Mental Component Summary Score at 2 Years

Time frame: Week 0 to Month 24

LTE Study: Change From Baseline in the Medical Outcome Study Short Form, SF-36, Version 2; Mental Component Summary Score at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Change From Baseline in the Medical Outcome Study Short Form, SF-36, Version 2; Mental Component Summary Score at 4 Years

Time frame: Week 0 to Month 48

LTE Study: Change From Baseline in the Medical Outcome Study Short Form,SF-36, Version 2; Physical Component Summary Score at 18 Months

Time frame: Week 0 to Month 18

LTE Study: Change From Baseline in the Medical Outcome Study Short Form, SF-36, Version 2; Physical Component Summary Score at 2 Years

Time frame: Week 0 to Month 24

LTE Study: Change From Baseline in the Medical Outcome Study Short Form, SF-36, Version 2; Physical Component Summary Score at 3 Years

Time frame: Week 0 to Month 36

LTE Study: Change From Baseline in the Medical Outcome Study Short Form, SF-36, Version 2; Physical Component Summary Score at 4 Years

Time frame: Week 0 to Month 48