Trial Outcomes & Findings for Apremilast Safety and PK Study in Recalcitrant Plaque Psoriasis (NCT NCT00521339)

NCT ID: NCT00521339

Last Updated: 2020-05-07

Results Overview

TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute \[NCI\] Common Toxicity Criteria for Adverse Events \[CTCAE\], Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death. Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: Week 0 to Week 12
• Results posted on: 2020-05-07

Participant Flow

Participants must have had a diagnosis of plaque-type psoriasis for at least 6 months and had an insufficient response, were unresponsive, intolerant of, or had medical contraindications to standard systemic therapy or biological treatment for plaque-type psoriasis. The study was conducted at 4 sites in the U.S. from 20 August 2007 to 12 May 2009.

The study consisted of a 12-week treatment phase, a 12-week treatment extension phase and a 4-week observational follow-up phase. Participants could enter the follow-up phase at any time during the study. Some participants had completed the study before the extension phase was added and therefore never had the opportunity to participate.

Participant milestones

Measure	Apremilast 20mg Participants received 20mg Apremilast capsules by mouth (PO) twice a day (BID) on Days 1 through 85 during the Treatment Phase	Apremilast 20mg/20mg Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were responders (achieved a 75% reduction in the Psoriasis Area Severity Index \[PASI-75\]) continued to receive 20 mg apremilast BID during the 12-week extension phase (Weeks 12-24).	Apremilast 20mg/30mg Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension phase
Treatment Phase STARTED	31	0	0
Treatment Phase Received Apremilast	30	0	0
Treatment Phase COMPLETED	19	0	0
Treatment Phase NOT COMPLETED	12	0	0
Treatment Extension Phase STARTED	0	4	7
Treatment Extension Phase COMPLETED	0	4	4
Treatment Extension Phase NOT COMPLETED	0	0	3
Observational Follow Up Phase STARTED	14	4	4
Observational Follow Up Phase COMPLETED	14	4	4
Observational Follow Up Phase NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Apremilast 20mg Participants received 20mg Apremilast capsules by mouth (PO) twice a day (BID) on Days 1 through 85 during the Treatment Phase	Apremilast 20mg/20mg Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were responders (achieved a 75% reduction in the Psoriasis Area Severity Index \[PASI-75\]) continued to receive 20 mg apremilast BID during the 12-week extension phase (Weeks 12-24).	Apremilast 20mg/30mg Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension phase
Treatment Phase Adverse Event	2	0	0
Treatment Phase Intolerability to study drug	2	0	0
Treatment Phase Lack of Efficacy	3	0	0
Treatment Phase Withdrawal by Subject	3	0	0
Treatment Phase Lost to Follow-up	1	0	0
Treatment Phase Protocol Violation	1	0	0
Treatment Extension Phase Withdrawal by Subject	0	0	2
Treatment Extension Phase Death	0	0	1

Baseline Characteristics

Apremilast Safety and PK Study in Recalcitrant Plaque Psoriasis

Baseline characteristics by cohort

Measure	Apremilast 20 mg (Treatment Phase) n=30 Participants Apremilast 20mg capsules by PO BID for Days 1 through 85 administered during the treatment phase
Age, Continuous	46.3 years STANDARD_DEVIATION 11.43 • n=93 Participants
Sex: Female, Male Female	11 Participants n=93 Participants
Sex: Female, Male Male	19 Participants n=93 Participants
Recalcitrant Psoriasis History	10.9 years STANDARD_DEVIATION 11.36 • n=93 Participants
Mean Psoriasis Area and Severity Index (PASI) Score	17.0 units on a scale STANDARD_DEVIATION 6.77 • n=93 Participants
Mean Body Surface Area (BSA) Involvement	22.4 Percentage of BSA STANDARD_DEVIATION 13.85 • n=93 Participants

PRIMARY outcome

Timeframe: Week 0 to Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication.

TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.

Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event.

Outcome measures

Measure	Apremilast 20 mg n=30 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase ≥ 1 AE	25 participants	—
Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase ≥ 1 AE with a suspected relationship to study drug	13 participants	—
Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase ≥ 1 severe AE	3 participants	—
Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase ≥ 1Severe AE suspected to be related to study drug	1 participants	—
Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase ≥ 1 SAE	0 participants	—
Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase ≥ AE leading to study drug discontinuation	4 participants	—
Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase >=1 treatment-related AE drug discontinued	2 participants	—

PRIMARY outcome

Timeframe: Week 12 to Week 24

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication in treatment Extension Phase.

TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.

Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event.

Outcome measures

Measure	Apremilast 20 mg n=4 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) n=7 Participants Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Treatment Emergent Adverse Events (TEAEs) During the Extension Phase ≥ 1 AE	4 participants	5 participants
Treatment Emergent Adverse Events (TEAEs) During the Extension Phase ≥ 1 AE with a suspected relationship to study drug	0 participants	2 participants
Treatment Emergent Adverse Events (TEAEs) During the Extension Phase ≥ 1 severe AE	1 participants	1 participants
Treatment Emergent Adverse Events (TEAEs) During the Extension Phase ≥ 1 SAE	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication. Last Observation Carried Forward.

The static Physician's Global Assessment (sPGA) rated the investigator's overall clinical assessment of a participants plaque thickness, erythema, and scaling on a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (majority of plaques have severe thickness, erythema, and scale). To assign a sPGA score, the investigator examined all psoriatic lesions and assigned a severity score ranging from 0 to 5 for thickness, erythema, and scaling. Scores for thickness, erythema, and scaling are summed and the mean of these 3 scores equals the overall sPGA score. Decreases in sPGA correspond to clinical improvement.

Outcome measures

Measure	Apremilast 20 mg n=30 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percentage of Participants With at Least a 1 Point Reduction on 0 to 5 Point Scale From Baseline in Static Physician Global Assessment (sPGA) at Week 12	66.7 percentage of participants Interval 47.2 to 82.7	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication.

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). 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. These values for each anatomic region are summed to yield the PASI score.

Outcome measures

Measure	Apremilast 20 mg n=20 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12	-59.0 percent change Standard Deviation 31.59	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication. If participant had a missing evaluation for any time point assessments, the last observation carried forward (LOCF) method of imputation was used.

PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 12. 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 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 the4 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.

Outcome measures

Measure	Apremilast 20 mg n=30 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percentage of Participants Who Achieved a PASI-75 Score at Week 12	30.00 percentage of participants Interval 14.7 to 49.4	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication. If participant had a missing evaluation for any time point assessments, the last observation carried forward (LOCF) method of imputation was used.

PASI -50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 12. 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 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 the4 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.

Outcome measures

Measure	Apremilast 20 mg n=30 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percentage of Participants Who Achieved a PASI-50 Score at Week 12	46.7 percentage of participants Interval 28.3 to 65.7	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Maximal PASI response was not analyzed since similar information was captured in change in psoriasis area severity Index (PASI) score at Day 85, which is week 12.

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). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication.

The BSA estimate was based on the palm area of the hand of the participant which equates to 1% of the total body surface area.

Outcome measures

Measure	Apremilast 20 mg n=20 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Psoriasis Affected Body Surface Area (BSA) Involvement at Week 12	-53.0 Percent change in BSA Standard Deviation 35.50	—

SECONDARY outcome

Population: Time to achieve PASI-50 was not analyzed since the study enrolled a small number of participants and the number of participants who achieved PASI-50 was even smaller.

Time to clinically relevant response (time to achieve PASI-50) during treatment phase was not analyzed. 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 the4 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. These values for each anatomic region are summed to yield the PASI score.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Time to achieve PASI-75 was not analyzed, due to the small number of participants enrolled and who achieved PASI-75.

Time to achieve PASI-75 during treatment phase was not analyzed. 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 the4 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. These values for each anatomic region are summed to yield the PASI score.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28-day Observational Follow-up Phase; Days 168 to Day 196.

Population: Time to relapse of psoriasis was not analyzed due to the small number of participants enrolled and who achieved PASI-50 and entered the observation follow-up phase.

Time to relapse of psoriasis (50% loss of maximal PASI score improvement in participants who achieved at least PASI-50 during the treatment phase) during the observational follow up phase was not analyzed. Time to relapse of psoriasis was defined as a 50% loss of maximal PASI score improvement in participants who achieved at least PASI-50 during the treatment or extension phase. The lesion on each area of the body was assessed for redness, thickness, and scaling.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication. Last observation carried forward was used. Only a small percentage of participants had psoriatic arthritis.

A participant was a responder if the following 3 criteria for improvement from baseline were met:

• ≥ 20% improvement in 78 tender joint count;
• ≥ 20% improvement in 76 swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.

Outcome measures

Measure	Apremilast 20 mg n=8 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent of Participants With Psoriatic Arthritis Who Achieved an American College of Rheumatology 20% Improvement (ACR-20) Response at Week 12	25.0 percentage of participants	—

SECONDARY outcome

Timeframe: Observational follow up phase; Days 168 to Day 196

Population: This endpoint was not summarized since there were only 8 participants with psoriatic arthritis enrolled in the study and only 2 participants who achieved an ACR 20 response during the treatment phase.

A relapse was defined as a 50% loss of maximal American College of Rheumatoid (ACR) Score improvement in participants with psoriatic arthritis who achieved at least an ACR 20 score during the treatment phase.

Relapses were only captured prior to the prescription of concomitant psoriatic treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for Apremilast.

Plasma concentrations of apremilast were determined using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). For Day 1, AUC0-12 was calculated, using linear trapezoidal area method in WinNonlin (linear-linear trapezoidal). For Days 85 and 169/170, the AUC during a dosing interval (12 hours) (AUC0-12), was calculated at steady-state using the partial area function within WinNonlin.

.

Outcome measures

Measure	Apremilast 20 mg n=10 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Area Under the Plasma Concentration Time-curve From 0 to 12 Hours Post Dose (AUC 0-12)	2424.48 ng*hr/mL Geometric Coefficient of Variation 46.87	—

SECONDARY outcome

Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for Apremilast.

The maximum observed plasma concentration of apremilast (Cmax); the maximum plasma concentration (Cmax) was obtained directly from the observed concentration-time data on Days 1, 85, and 169/170, respectively.

Outcome measures

Measure	Apremilast 20 mg n=10 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Peak (Maximum) Plasma Concentration of Medication (Cmax)	364.85 ng/mL Geometric Coefficient of Variation 38.25	—

SECONDARY outcome

Timeframe: Day 85 Pre-dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast

The trough observed plasma concentration of apremilast (Cmin) was determined directly from the observed pre-AM dose concentration on Day 85.

Outcome measures

Measure	Apremilast 20 mg n=10 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Trough Plasma Concentration (Cmin)	101.36 ng/mL Geometric Coefficient of Variation 71.6	—

SECONDARY outcome

Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast.

The time to reach Cmax (Tmax) was obtained directly from the observed concentration-time data on Day 85. Actual times utilized were used for reporting Tmax values.

Outcome measures

Measure	Apremilast 20 mg n=10 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Time to Maximum Plasma Concentration (Tmax) During the Treatment Phase	2.00 hours Interval 1.0 to 4.03	—

SECONDARY outcome

Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast.

Terminal phase elimination half-life (t1/2) was calculated as follows: t1/2 = 0.693/λz. The terminal elimination rate constant (λZ) was estimated by linear regression of the log-transformed concentration-time data.

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Terminal Phase Elimination Half Life of Apremilast (t½)	7.832 Liters Geometric Coefficient of Variation 26.031	—

SECONDARY outcome

Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast. This analysis was performed for participants with normal renal function only.

The apparent total clearance of apremilast from plasma after extravascular administration (CLz/F); for Day 1, apparent clearance of drug from plasma (CL/F) was not calculated.

For Day 85, Apparent clearance of drug from plasma after extravascular administration (CL/F) was calculated as follows: CL/F= Dose/AUC^12 where τ=12.

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Apparent Total Clearance of Apremilast From Plasma After Extravascular Administration (CLz/F) During the Treatment Phase	8249.19 mL/hour Geometric Coefficient of Variation 46.87	—

SECONDARY outcome

Timeframe: Day 85

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast.

Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) (for Days 1, 85, and 169/170)

1. For Day 1, Vz/F was not calculated.

2. For Days 85 and 169/170, apparent volume of distribution of drug (V/z) based on the terminal phase was calculated as follows: Vz/F=Dose/(λ*AUC^12)

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Apparent Total Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) During the Treatment Phase	107616.08 mL Geometric Coefficient of Variation 47.03	—

SECONDARY outcome

Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast.

Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug.

Outcome measures

Measure	Apremilast 20 mg n=10 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Accumulation Index (R)	1.68 ratio Geometric Coefficient of Variation 53.17	—

SECONDARY outcome

Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast

Mean Residence Time (MRT) is defined as the mean duration of time the drug spends in the body. The average concentration at steady state (Cavg) (for Day 85 was calculated as follows: Cavg = (Day 85 AUC0-12)/(12).

Outcome measures

Measure	Apremilast 20 mg n=10 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Mean Residence Time (MRT) During the Treatment Phase	202.04 hours Geometric Coefficient of Variation 46.87	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the peripheral blood T cell, B cell and NK cell subsets at Baseline and Week 12.

T cells or T lymphocytes, a type of white blood cell, play a role in cell-mediated immunity. T cells are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on the cell surface and mature in the thymus. B cells, a type of lymphocyte in the humoral immunity of the adaptive immune system can be distinguished by the presence of a protein on the B cells outer surface called a B cell receptor (BCR). This receptor protein allows a B cell to bind to a specific antigen and make antibodies against antigens [(antigen-presenting cells APCs)], and to develop into memory B cells after activation by antigen interaction. Natural Killer Cells (NK) are a type of cytotoxic lymphocyte critical to the innate immune system. Their role is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. They constitute the third kind of cells differentiated from the common lymphoid progenitor generating B and T lymphocytes and mature in the bone marrow.

Outcome measures

Measure	Apremilast 20 mg n=30 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Change From Baseline in Peripheral Blood T Cell, B Cell, and NK Cell Subsets at Week 12 CD 16 + CD 56 (NK cells)	-0.7 percentage of lymphocytes Standard Deviation 3.05	—
Change From Baseline in Peripheral Blood T Cell, B Cell, and NK Cell Subsets at Week 12 CD 19 (B-cells)	-0.5 percentage of lymphocytes Standard Deviation 2.63	—
Change From Baseline in Peripheral Blood T Cell, B Cell, and NK Cell Subsets at Week 12 CD 3 (T-cells)	0.6 percentage of lymphocytes Standard Deviation 2.63	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=16 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of CD3 in the Dermis of the Psoriatic Skin Biopsy at Week 12	-62.0 percent change Interval -84.3 to 290.9	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=16 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of CD3 in the Epidermis of the Psoriatic Skin Biopsy at Week 12	-47.4 percent change Interval -100.0 to 159.5	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=15 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of CD 11c in the Dermis of the Psoriatic Skin Biopsy at Week 12	-54.6 percent change Interval -88.8 to 284.0	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=14 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of CD11c in the Epidermis of the Psoriatic Skin Biopsy at Week 12	-88.6 percent change Interval -100.0 to 46.3	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=16 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of CD56 in the Dermis of the Psoriatic Skin Biopsy at Week 12	-12.5 percent change Interval -68.9 to 57.1	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=13 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of CD56 in the Epidermis of the Psoriatic Skin Biopsy at Week 12	-73.3 percent change Interval -100.0 to 311.1	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=13 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of Langerin in the Dermis of Psoriatic Skin Biopsy at Week 12	-57.9 percent change Interval -100.0 to 178.3	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=16 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of Langerin in the Epidermis of the Psoriatic Skin Biopsy at Week 12	17.1 percent change Interval -78.7 to 300.0	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Psoriatic Skin Biopsy at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

Outcome measures

Measure	Apremilast 20 mg n=15 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline of Epidermal Thickness in the Psoriatic Skin Biopsy at Week 12	-34.3 percent change Interval -65.4 to 42.2	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=12 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Inducible Nitric Oxide (iNOS) Inflammatory Marker in Psoriatic Skin Biopsies	-100.0 percent change Interval -100.0 to 55.9	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=6 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Interleukin (IL) IL-22 Inflammatory Marker in Psoriatic Skin Biopsies	-100.0 percent change Interval -100.0 to -44.5	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=8 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the p40 Inflammatory Marker in Psoriatic Skin Biopsies	-86.7 percent change Interval -100.0 to 51.7	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) i being measured.

Outcome measures

Measure	Apremilast 20 mg n=11 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Defensin Beta 4 (DEFB4) Inflammatory Marker in Psoriatic Skin Biopsies	-82.3 percent change Interval -100.0 to 14.5	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=15 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the keratin16 (K16) Inflammatory Marker in Psoriatic Skin Biopsies	-78.6 percent change Interval -99.9 to 217.7	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=15 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the pluripotent19 (P19) Inflammatory Marker in Psoriatic Skin Biopsies	-68.3 percent change Interval -100.0 to 326.6	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=15 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the IL8 Inflammatory Marker in Psoriatic Skin Biopsies	-66.5 percent change Interval -100.0 to 136.2	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=12 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the MX1 (Gene That Encodes the Interferon-induced p78 Protein) Inflammatory Marker in Psoriatic Skin Biopsies	-52.6 percent change Interval -97.0 to -1.3	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=11 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the IL17A Inflammatory Marker in Psoriatic Skin Biopsies	-49.4 percent change Interval -100.0 to 76.8	—

SECONDARY outcome

Timeframe: Week 0 to Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=14 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Tumor Necrosing Factor (TNF) Alpha Inflammatory Marker in Psoriatic Skin Biopsies	-42.7 percent change Interval -100.0 to 242.9	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=13 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Interferon (INF) Gamma Inflammatory Marker in Psoriatic Skin Biopsies	-37.6 percent change Interval -100.0 to 250.3	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=15 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the IL10 Inflammatory Marker in Psoriatic Skin Biopsies	-26.5 percent change Interval -100.0 to 565.0	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=12 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Chemokine Ligand (CXCL9) Inflammatory Marker in Psoriatic Skin Biopsies	-36.4 percent change Interval -97.1 to 1021.2	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=10 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the IL2 Inflammatory Marker in Psoriatic Skin Biopsies	-25.0 percent change Interval -100.0 to 875.7	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Population includes participants who took at least 1 dose of study medication and were measured for the Inflammatory Marker in Psoriatic Skin Biopsies at Baseline and Week 12. Participation was optional for the pharmacodynamic portion of the study.

Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

Outcome measures

Measure	Apremilast 20 mg n=12 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Percent Change From Baseline in the Dendritic Cell (CD83) Inflammatory Marker in Psoriatic Skin Biopsies	14.2 percent change Interval -98.5 to 162.1	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Only those with both a baseline and final/termination visit assessment were included in the analyses of change from baseline. Safety population consisted of all participants who were enrolled and received at least one dose of study medication.

DLQI was the dermatology-specific quality of life (QOL) measure used for the psoriatic population. The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on a participants QoL, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Possible responses for each of the 10 items are: not at all, a little, a lot, and very much. Each question is rated on a scale of 0 to 3 with a total range of 0 to 30. Higher scores indicate greater impact of disease on QOL

Outcome measures

Measure	Apremilast 20 mg n=30 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 12	-4.7 units on a scale Standard Deviation 8.66	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Safety population consisted of all participants who were enrolled and received at least one dose of study medication. If participant had a missing evaluation for any time point assessments, the last observation carried forward (LOCF) method of imputation was used.

The SF-36 was a self-administered instrument consisting of 8 multi-item scales that assess 8 health domains: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. A higher score post-baseline is indicative of improvement in the disease state. The summary physical health score included physical functioning, role-physical, bodily pain and general health. The summary mental health score included: vitality, social functioning, role-emotional and mental health. The resulting score for each subscale is then standardized, to obtain values ranging from 0 to 100, with higher values indicating a better QOL.

Outcome measures

Measure	Apremilast 20 mg n=15 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Change From Baseline in the Medical Outcome Study Short Form 36-item Health Survey (SF-36) Scores, Mental and Physical Components to Week 12 Mental Component	0.8 units on a scale Standard Deviation 7.45	—
Change From Baseline in the Medical Outcome Study Short Form 36-item Health Survey (SF-36) Scores, Mental and Physical Components to Week 12 Physical Component	2.4 units on a scale Standard Deviation 7.64	—

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast.

Plasma concentrations of apremilast were determined using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS).

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Area Under the Plasma Concentration Time-curve From 0 to 12 Hours Post Dose (AUC 0-12) During the Extension Phase	2019.71 ng*hr/mL Geometric Coefficient of Variation 63.62	—

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for Apremilast.

The maximum observed plasma concentration of CC-10004 (Cmax); the maximum plasma concentration (Cmax) was obtained directly from the observed concentration-time data on Days 169/170.

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Peak (Maximum) Plasma Concentration of Apremilast (Cmax) During the Extension Phase	320.35 ng/mL Geometric Coefficient of Variation 47.64	—

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for Apremilast.

The time to reach Cmax (Tmax) was obtained directly from the observed concentration-time data on Day 169/170. Actual times utilized were used for reporting Tmax values.

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Time to Maximum Plasma Concentration (Tmax) During the Extension Phase	1.59 hours Geometric Coefficient of Variation 42	—

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for Apremilast.

Terminal phase elimination half-life (t1/2) was calculated as follows: t1/2 = 0.693/λz. The terminal elimination rate constant (λZ) was estimated by linear regression of the log-transformed concentration-time data.

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Terminal Phase Elimination Half Life of Apremilast (t½) During the Extension Phase	6.287 hours Geometric Coefficient of Variation 22.879	—

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast. This analysis was performed for participants with normal renal function only.

For 169/170, apparent clearance of drug from plasma after extravascular administration (CL/F) was calculated as follows: CL/F= Dose/AUC12

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Apparent Total Clearance of Apremilast From Plasma After Extravascular Administration (CL/F) During the Extension Phase	14853.59 mL/hour Geometric Coefficient of Variation 63.62	—

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast.

For Days 169/170, apparent volume of distribution of drug (V/z) based on the terminal phase was calculated as follows: Vz/F=Dose/(λ*AUC12) where λ = the terminal elimination rate constant

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Apparent Total Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) During the Extension Phase	134734.60 mL Geometric Coefficient of Variation 63.70	—

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Not able to calculate the Accumulation Index at this time point; insufficient data collection for this calculation.

Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Population: Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma concentration data for apremilast.

Mean Residence Time (MRT) is defined as the mean duration of time the drug spends in the body. The average concentration at steady state (Cavg) (for Days169/170) was calculated as follows: Cavg = (Day 169/170)/(12)

Outcome measures

Measure	Apremilast 20 mg n=3 Participants Apremilast 20mg capsules PO BID on Days 1 through 85 administered during the Treatment Phase	Apremilast 20mg/30mg (Extension Phase) Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Mean Residence Time (MRT) During the Extension Phase	168.3092 hours Geometric Coefficient of Variation 63.6203	—

Adverse Events

Apremilast 20 mg (Treatment Phase)

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Apremilast 20mg/20mg (Extension Phase)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Apremilast 20mg/30mg (Extension Phase)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Apremilast 20 mg (Treatment Phase) n=30 participants at risk Apremilast 20mg capsules by mouth (PO) twice a day (BID) for Days 1 through 85 administered during the treatment phase	Apremilast 20mg/20mg (Extension Phase) n=4 participants at risk Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were responders (achieved a 75% reduction in the Psoriasis Area Severity Index \[PASI-75\]) continued to receive 20 mg apremilast BID during the 12-week extension phase (Weeks 12-24).	Apremilast 20mg/30mg (Extension Phase) n=7 participants at risk Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Cardiac disorders ARRHYTHMIA	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Cardiac disorders HYPERTENSIVE HEART DISEASE	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.

Other adverse events

Measure	Apremilast 20 mg (Treatment Phase) n=30 participants at risk Apremilast 20mg capsules by mouth (PO) twice a day (BID) for Days 1 through 85 administered during the treatment phase	Apremilast 20mg/20mg (Extension Phase) n=4 participants at risk Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were responders (achieved a 75% reduction in the Psoriasis Area Severity Index \[PASI-75\]) continued to receive 20 mg apremilast BID during the 12-week extension phase (Weeks 12-24).	Apremilast 20mg/30mg (Extension Phase) n=7 participants at risk Participants who received 20 mg apremilast BID during the treatment phase (Weeks 0-12) who were non-responders (did not achieve PASI-75 response) received 30 mg apremilast BID during the 12-week extension
Infections and infestations NASOPHARYNGITIS	3.3% 1/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Infections and infestations BRONCHITIS	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	3.3% 1/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Infections and infestations SINUSITIS	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
General disorders CYST	6.7% 2/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Gastrointestinal disorders DIARRHOEA	23.3% 7/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Gastrointestinal disorders DYSPEPSIA	6.7% 2/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Gastrointestinal disorders NAUSEA	20.0% 6/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
General disorders FATIGUE	16.7% 5/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Nervous system disorders HEADACHE	20.0% 6/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Respiratory, thoracic and mediastinal disorders SINUS CONGESTION	6.7% 2/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Skin and subcutaneous tissue disorders PRURITUS	6.7% 2/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	28.6% 2/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Musculoskeletal and connective tissue disorders BACK PAIN	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Musculoskeletal and connective tissue disorders NECK PAIN	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
General disorders INFLUENZA LIKE ILLNESS	3.3% 1/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
General disorders OEDEMA PERIPHERAL	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	3.3% 1/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	28.6% 2/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Respiratory, thoracic and mediastinal disorders PRODUCTIVE COUGH	3.3% 1/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Respiratory, thoracic and mediastinal disorders RESPIRATORY TRACT CONGESTION	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Nervous system disorders MIGRAINE	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Nervous system disorders SCIATICA	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Gastrointestinal disorders FLATULENCE	3.3% 1/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Injury, poisoning and procedural complications CORNEAL ABRASION	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Injury, poisoning and procedural complications JOINT DISLOCATION	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	25.0% 1/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LIPOMA	0.00% 0/30 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	0.00% 0/4 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.	14.3% 1/7 • Days 1 to Day 196 visit; Adverse Events (AE) were reported from the first day of study drug treatment through the 28 day observational follow up period. Maximum exposure to study medication was 171 days.

Additional Information

Anne McClain

Celgene Corporation

Phone: 1-888-260-1599

Email: clinicaltrialdisclosure@celgene.com

Results disclosure agreements

• Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
• Publication restrictions are in place

Restriction type: OTHER