Psoriasis
Conditions
Keywords
Apremilast, CC-10004, Quality of life, Safety, Efficacy, Psoriasis manifestations
Brief summary
The primary objective of the study is to assess the impact of treatment with apremilast 30 mg twice daily for 16 weeks, compared to placebo, on health-related quality of life (QOL) in adults with manifestations of plaque psoriasis and impaired quality of life.
Detailed description
Participants will be randomized 2 (apremilast):1 (placebo) in approximately 10 countries in Western Europe. Participants will be block-randomized to each of the manifestations of psoriasis (scalp psoriasis, nail psoriasis, palmoplantar psoriasis, genital psoriasis, and psoriasis in visible locations). Participants presenting with multiple manifestations will be allocated to the manifestation which is most severe, as determined by the participant. All manifestations will be assessed for efficacy at each study visit. The study will consist of 4 phases: * Screening Phase - up to 5 weeks (35 days) * Double-blind Placebo-controlled Phase - Weeks 0 to 16 Participants will receive treatment with either apremilast or matched placebo. * Apremilast Extension Phase - Weeks 16 through 52 All participants will be switched to (or continue with) apremilast at week 16 and will maintain this dosing through week 52. * Post-treatment Observational Follow-up Phase 4-week post-treatment observational follow-up phase for all participants who complete the study on treatment or discontinue from the study treatment early.
Interventions
DRUGApremilast
Apremilast 30 mg tablets taken orally twice a day.
DRUGPlacebo
Placebo tablets taken orally twice a day
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must satisfy the following criteria to be enrolled in the study: 1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF). 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 4. Subject has diagnosis of chronic plaque psoriasis for at least 6 months prior to baseline, that cannot be controlled by topical therapy. 5. Subject has a PASI score ranging from ≥ 3 to ≤ 10 at baseline. 6. Subject has a DLQI score \> 10 at baseline. 7. Subject has presence of ≥ 1 clinical manifestations of plaque psoriasis, defined as at least one of the following: 1. Moderate to severe scalp psoriasis, defined as Scalp Physician Global Assessment (ScPGA) ≥ 3 2. Nail psoriasis, defined as onycholysis and onychodystrophy in at least 2 fingernails 3. Moderate to severe genital plaque psoriasis, defined as modified static Physicians Global Assessment of Genitalia (sPGA-G) ≥ 3 4. Moderate to severe palmoplantar psoriasis, defined as Palmoplantar Psoriasis Physicians Global Assessment (PPPGA) ≥ 3 5. Moderate to severe plaque psoriasis in visible locations (dorsal hand, face, neck, and hairline) with static Physicians Global Assessment (sPGA) ≥ 3 8. Subject must be in general good health (except for psoriasis) as judged by the Investigator, based on medical history, physical examination, and clinical laboratories. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions.) 9. Subject must have failed to respond to, or be contraindicated to, or intolerant to other systemic therapy, including, but not limited to, cyclosporine, methotrexate, acitretin, psoralen and ultraviolet-A-light (PUVA) fumaric acid esters or biologic therapies. 10. Subjects (in Italy only) must be non-responder to, contraindicated to, or intolerant to other systemic therapy (including cyclosporine, methotrexate, or PUVA) AND also be contraindicated to, or intolerant to biologics. 11. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]) PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. NOTE: Option 2 may not be acceptable as a highly effective contraception option in all countries per local guidelines/regulations.
Exclusion criteria
The presence of any of the following will exclude a subject from enrollment: 1. Subject has any condition, including other inflammatory diseases or dermatologic conditions, which confounds the ability to interpret data from the study, including other types of psoriasis (ie, erythrodermic, or guttate), other than plaque psoriasis or inverse psoriasis. 2. Subject has history of drug-induced psoriasis. 3. Subject has arthritis that requires systemic treatment. 4. Subject unable to avoid use of tanning booths for at least 4 weeks prior to baseline and during study. 5. Subject is currently enrolled in any other clinical trial involving an investigational product. 6. Other than psoriasis, subject has history of clinically significant or uncontrolled disease (as determined by the Investigator), including the presence of laboratory abnormalities, cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease, which places the subject at unacceptable risk if he/she were to participate in the study 7. Prior history of suicide attempt at any time in the subject's lifetime prior to signing the informed consent, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent. 8. Subjects with severe renal impairment, defined by estimated glomerular filtration rate (eGFR) or creatinine clearance (CLcr) less than 30 mL/min, are also categorized as having Stage 4 chronic kidney disease (CKD), and are excluded from the study. 9. Malignancy or history of malignancy or myeloproliferative or lymphoproliferative disease within the past 3 years, except for treated (ie, cured) basal cell or squamous cell in situ skin carcinomas. 10. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed and the infection cured, at least 4 weeks prior to Screening and no new or recurrent infections prior to the Baseline Visit. 11. Subject has received a live vaccine within 3 months of baseline or plans to do so during study. 12. Subject is a pregnant or breastfeeding (lactating) woman. 13. Subject has used topical therapy within 2 weeks of randomization (including, but not limited to, topical corticosteroids, retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, anthralin/dithranol, or moisturizers which contain urea or salicylic acid). Use of phototherapy within 4 weeks prior to randomization. Use of conventional systemic therapy or systemic corticosteroids within 4 weeks prior to randomization, except for conditions other than psoriasis or psoriatic arthritis. Use of biologic therapy within 5 pharmacokinetic half-lives. 14. Prior treatment with apremilast, or participation in a clinical study, involving apremilast. 15. Subject has any condition that confounds the ability to interpret data from the study. 16. Subject has history of allergy or hypersensitivity to any components of the IP (including placebo). 17. Subject has rare hereditary problem of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption. 18. Subject's most severe manifestation corresponds to a manifestation whose randomization block has already been fully enrolled.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline and week 16 | The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life (QOL). The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16 | Baseline and week 16 | Body surface area is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA. |
| Change From Baseline in Itch Numeric Rating Scale (NRS) Score at Week 16 | Baseline and week 16 | The Itch Numeric Rating Scale (NRS) asked participants to assess the worst severity of itch experienced over the past 24 hours on an 11-point scale anchored from 0, representing 'no itching' to 10, representing 'worst itch imaginable'. A negative change from baseline indicates improvement in itch severity. |
| Change From Baseline in Skin Discomfort/Pain Visual Analog Scale (VAS) at Week 16 | Baseline and week 16 | Participants were asked to indicate their level of skin discomfort/pain in the past week by placing a vertical stroke on a 100 mm horizontal line on which the left-hand boundary (0) represents no skin discomfort/pain, and the right-hand boundary (100) represents worst possible skin discomfort/pain. The distance from the mark to the left-hand boundary was recorded. A negative change from baseline indicates improvement in skin discomfort/pain. |
| Percentage of Participants Who Achieved a Psoriasis Area Severity Index (PASI) Score < 3 at Week 16 | Week 16 | The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. 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 and the values for each anatomic region are summed to yield the PASI score. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. |
| Percentage of Participants Who Achieved a Patient Benefit Index (PBI) Global Score of ≥ 1 at Week 16 | Week 16 | The PBI is a validated patient-reported instrument to assess patient-relevant benefits of psoriasis treatment. Prior to starting study treatment, participants were asked to assess the importance of a series of treatment goals (from not important to very important) by completing the Patient Needs Questionnaire (PNQ). After a period of treatment (16 weeks), participants were then asked to assess the extent to which these goals were achieved (from not at all to very) by completing the Patient Benefit Questionnaire (PBQ). The Patient Benefit Index represents the benefits realized as a function of most important needs. The PBI score ranges from 0 (no benefit) to 4 (maximum benefit). |
| Percent Change From Baseline in European Quality of Life 5-Dimension (EQ-5D) VAS Score at Week 16 | Baseline and week 16 | EQ-5D measures the participant's general health state on a vertical VAS and five quality of life domains. The EQ-5D VAS score ranges from 0 to 100, where a score of 0 indicates the worst imaginable health states and a score of 100 indicates the best imaginable health state. A positive change from baseline indicates improvement. |
| Percent Change From Baseline in EQ-5D Index Score at Week 16 | Baseline and week 16 | EQ-5D measures the participants general health state as a vertical VAS and 5 quality of life domains: mobility, self-care, main activity (work, study, housework, family/leisure activities), pain/discomfort, and anxiety/depression. Each dimension is rated on three levels (no problems, some/moderate problems, extreme problems). An EQ-5D summary index is derived by applying a formula that attaches values (weights) to each of the levels in each dimension. EQ-5D index values were derived using the UK scoring algorithm, where a higher score indicates a better health state. The range of the score is from -0.224 to 1, with 0 corresponding to death, 1 corresponding to full health, and negative numbers indicate health states worse than death. A positive change from baseline indicates improvement. |
| Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO) at Week 16: Percentage Work Time Missed | Baseline and week 16 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent of work time missed is derived from the number of hours of work missed due to psoriasis symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed, and a negative change from baseline indicates improvement. |
| Change From Baseline in WPAI: PSO at Week 16: Percentage Work Impairment | Baseline and week 16 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent impairment while working was derived from the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. |
| Change From Baseline in WPAI: PSO at Week 16: Percentage Overall Work Impairment | Baseline and week 16 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent overall work impairment takes into account both hours missed due to psoriasis symptoms and the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. |
| Change From Baseline in WPAI: PSO at Week 16: Percentage Activity Impairment | Baseline and week 16 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which psoriasis affected their regular daily unpaid activities, measured on a VAS from 1 (no effect on daily activities) to 10 (psoriasis completely prevented daily activities). A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | From first dose of study drug to week 16 or up to 28 days after last dose for participants who didn't enter the apremilast extension period. | An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening of a preexisting condition was considered an AE. A serious adverse event (SAE) is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. The Investigator assessed the severity/intensity of each event as mild, moderate, or severe based on level of symptoms. |
| Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | 16 weeks | Marked laboratory abnormalities are defined for each parameter below. ULN = upper limit of normal |
| Change From Baseline in Blood Pressure During the Placebo-controlled Period | Baseline, week 2, week 4, and week 16 | — |
| Change From Baseline in Pulse Rate During the Placebo-controlled Period | Baseline and week 2, week 4, and week 16 | — |
| Change From Baseline in Body Weight During the Placebo-controlled Period | Baseline and week 2, week 4, and week 16 | — |
| Change From Baseline in Waist Circumference During the Placebo-controlled Period | Baseline and week 2, week 4, and week 16 | — |
| Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in DLQI at Weeks 32 and 52 | Baseline, week 32 and week 52 | The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life (QOL). The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. |
| Change From Baseline in DLQI at Week 16 | Baseline and week 16 | The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life. The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. A negative change from baseline indicates improvement in quality of life. |
| Change From Baseline in Itch NRS Score at Weeks 32 and 52 | Baseline, week 32 and week 52 | The Itch Numeric Rating Scale (NRS) asked participants to assess the worst severity of itch experienced over the past 24 hours on an 11-point scale anchored from 0, representing 'no itching' to 10, representing 'worst itch imaginable'. A negative change from baseline indicates improvement in itch severity. |
| Change From Baseline in Skin Discomfort/Pain VAS at Weeks 32 and 52 | Baseline, week 32 and week 52 | Participants were asked to indicate their level of skin discomfort/pain in the past week by placing a vertical stroke on a 100 mm horizontal line on which the left-hand boundary (0) represents no skin discomfort/pain, and the right-hand boundary (100) represents worst possible skin discomfort/pain. The distance from the mark to the left-hand boundary was recorded. A negative change from baseline indicates improvement in skin discomfort/pain. |
| Percent Change From Baseline in BSA Affected by Psoriasis at Weeks 32 and 52 | Baseline, week 32 and week 52 | Body surface area is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA. |
| Percentage of Participants Who Achieved a PBI Score of ≥ 1 at Weeks 32 and 52 | Week 32 and week 52 | The PBI is a validated patient-reported instrument to assess patient-relevant benefits of psoriasis treatment. Prior to starting study treatment, participants were asked to assess the importance of a series of treatment goals (from not important to very important) by completing the Patient Needs Questionnaire (PNQ). After a period of treatment (32 weeks and 52 weeks), participants were then asked to assess the extent to which these goals were achieved (from not at all to very) by completing the Patient Benefit Questionnaire (PBQ). The Patient Benefit Index represents the benefits realized as a function of most important needs. The PBI score ranges from 0 (no benefit) to 4 (maximum benefit). |
| Percentage of Participants Who Achieved a PASI Score < 3 at Weeks 32 and 52 | Week 32 and week 52 | The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. 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 and the values for each anatomic region are summed to yield the PASI score. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. |
| Percent Change From Baseline in EQ-5D VAS Score at Week 52 | Baseline and week 52 | EQ-5D measures the participant's general health state on a vertical VAS and five quality of life domains. The EQ-5D VAS score ranges from 0 to 100, where a score of 0 indicates the worst imaginable health states and a score of 100 indicates the best imaginable health state. A positive change from baseline indicates improvement. |
| Percent Change From Baseline in EQ-5D Index Score at Week 52 | Baseline and week 52 | EQ-5D measures the participants general health state as a vertical VAS and 5 quality of life domains: mobility, self-care, main activity (work, study, housework, family/leisure activities), pain/discomfort, and anxiety/depression. Each dimension is rated on three levels (no problems, some/moderate problems, extreme problems). An EQ-5D summary index is derived by applying a formula that attaches values (weights) to each of the levels in each dimension. EQ-5D index values were derived using the UK scoring algorithm, where a higher score indicates a better health state. The range of the score is from -0.224 to 1, with 0 corresponding to death, 1 corresponding to full health, and negative numbers indicate health states worse than death. A positive change from baseline indicates improvement. |
| Change From Baseline in WPAI: PSO at Week 52: Percentage Work Time Missed | Baseline and week 52 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent of work time missed is derived from the number of hours of work missed due to psoriasis symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed, and a negative change from baseline indicates improvement. |
| Change From Baseline in WPAI: PSO at Week 52: Percentage Work Impairment | Baseline and week 52 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent impairment while working was derived from the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. |
| Change From Baseline in WPAI: PSO at Week 52: Percentage Overall Work Impairment | Baseline and week 52 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent overall work impairment takes into account both hours missed due to psoriasis symptoms and the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. |
| Change From Baseline in WPAI: PSO at Week 52: Percentage Activity Impairment | Baseline and week 52 | The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which psoriasis affected their regular daily unpaid activities, measured on a VAS from 1 (no effect on daily activities) to 10 (psoriasis completely prevented daily activities). A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. |
| Number of Participants With TEAEs During Apremilast Treatment | From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast. | An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening of a preexisting condition was considered an AE. A serious adverse event (SAE) is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. The Investigator assessed the severity/intensity of each event as mild, moderate, or severe based on level of symptoms. |
| Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast. | — |
| Change From Baseline in Blood Pressure at End of Apremilast Extension Period | Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52 | — |
| Change From Baseline in Pulse Rate at End of Apremilast Extension Period | Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52 | — |
| Change From Baseline in Body Weight at End of Apremilast Extension Period | Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52 | — |
| Change From Baseline in Waist Circumference at End of Apremilast Extension Period | Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52 | — |
| Change From Baseline in DLQI at Weeks 32 and 52 | Baseline, week 32 and week 52 | The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life. The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. A negative change from baseline indicates improvement in quality of life. |
Countries
France, Germany, Italy, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
Eligible participants were enrolled at 55 centers in France, Germany, Italy, Spain, Switzerland, and the United Kingdom. The study consisted of a 16-week placebo-controlled period and a 36-week apremilast extension period.
Pre-assignment details
Participants were randomized in a 1:2 ratio to receive placebo or apremilast. Participants were block-randomized to each of the manifestations of psoriasis (scalp psoriasis, nail psoriasis, palmoplantar psoriasis, genital psoriasis, and psoriasis in visible locations).
Participants by arm
| Arm | Count |
|---|---|
| Placebo / Apremilast 30 mg Participants received placebo tablets orally twice a day for 16 weeks. At Week 16 participants switched to receive 30 mg apremilast orally twice a day up to week 52. | 92 |
| Apremilast 30 mg Participants received apremilast 30 mg tablets orally twice a day for 52 weeks. | 185 |
| Total | 277 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Apremilast Extension Period (Week 16-52) | Adverse Event | 6 | 9 |
| Apremilast Extension Period (Week 16-52) | Lack of Efficacy | 2 | 11 |
| Apremilast Extension Period (Week 16-52) | Lost to Follow-up | 0 | 3 |
| Apremilast Extension Period (Week 16-52) | Non-compliance with Study Drug | 0 | 2 |
| Apremilast Extension Period (Week 16-52) | Other | 1 | 1 |
| Apremilast Extension Period (Week 16-52) | Protocol Deviation | 0 | 1 |
| Apremilast Extension Period (Week 16-52) | Withdrawal by Subject | 7 | 20 |
| Placebo-controlled Period (Week 1-16) | Adverse Event | 8 | 16 |
| Placebo-controlled Period (Week 1-16) | Lack of Efficacy | 2 | 4 |
| Placebo-controlled Period (Week 1-16) | Lost to Follow-up | 0 | 2 |
| Placebo-controlled Period (Week 1-16) | Protocol Deviation | 0 | 1 |
| Placebo-controlled Period (Week 1-16) | Reason Unknown | 1 | 0 |
| Placebo-controlled Period (Week 1-16) | Withdrawal by Subject | 12 | 10 |
Baseline characteristics
| Characteristic | Placebo / Apremilast 30 mg | Apremilast 30 mg | Total |
|---|---|---|---|
| Age, Continuous | 50.9 years STANDARD_DEVIATION 13.68 | 47.4 years STANDARD_DEVIATION 14.28 | 48.6 years STANDARD_DEVIATION 14.16 |
| Age, Customized < 65 years | 73 Participants | 158 Participants | 231 Participants |
| Age, Customized ≥ 65 years | 19 Participants | 27 Participants | 46 Participants |
| Dermatology Life Quality Index (DLQI) Score | 18.5 score on a scale STANDARD_DEVIATION 4.94 | 18.1 score on a scale STANDARD_DEVIATION 4.86 | 18.2 score on a scale STANDARD_DEVIATION 4.88 |
| Duration of Plaque Psoriasis | 18.41 years STANDARD_DEVIATION 13.35 | 16.31 years STANDARD_DEVIATION 13.116 | 17.01 years STANDARD_DEVIATION 13.207 |
| Primary Manifestations for Stratifications Genital Psoriasis | 15 Participants | 28 Participants | 43 Participants |
| Primary Manifestations for Stratifications Nail Psoriasis | 20 Participants | 40 Participants | 60 Participants |
| Primary Manifestations for Stratifications Palmoplantar Psoriasis | 10 Participants | 22 Participants | 32 Participants |
| Primary Manifestations for Stratifications Psoriasis in Visible Locations | 24 Participants | 50 Participants | 74 Participants |
| Primary Manifestations for Stratifications Scalp Psoriasis | 23 Participants | 45 Participants | 68 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Collected or Unknown | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 89 Participants | 179 Participants | 268 Participants |
| Region of Enrollment France | 6 Participants | 13 Participants | 19 Participants |
| Region of Enrollment Germany | 45 Participants | 102 Participants | 147 Participants |
| Region of Enrollment Italy | 8 Participants | 11 Participants | 19 Participants |
| Region of Enrollment Spain | 23 Participants | 24 Participants | 47 Participants |
| Region of Enrollment Switzerland | 1 Participants | 7 Participants | 8 Participants |
| Region of Enrollment United Kingdom | 9 Participants | 28 Participants | 37 Participants |
| Sex: Female, Male Female | 35 Participants | 79 Participants | 114 Participants |
| Sex: Female, Male Male | 57 Participants | 106 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 185 | 0 / 221 |
| other Total, other adverse events | 38 / 92 | 113 / 185 | 93 / 221 |
| serious Total, serious adverse events | 0 / 92 | 8 / 185 | 12 / 221 |
Outcome results
Primary
Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life (QOL). The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL.
Time frame: Baseline and week 16
Population: All randomized participants; Missing data at week 16 were imputed using multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | 41.3 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | 73.3 percentage of participants |
p-value: <0.000195% CI: [18.6, 45.2]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Blood Pressure at End of Apremilast Extension Period
Time frame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
Population: Randomized participants who received at least 1 dose of apremilast, ie, participants originally randomized to apremilast and participants originally randomized to placebo who entered the apremilast extension phase, with a baseline value and at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Pressure at End of Apremilast Extension Period | Systolic | 0.1 mmHg | Standard Deviation 13.68 |
| Placebo | Change From Baseline in Blood Pressure at End of Apremilast Extension Period | Diastolic | 0.1 mmHg | Standard Deviation 8.98 |
Secondary
Change From Baseline in Blood Pressure During the Placebo-controlled Period
Time frame: Baseline, week 2, week 4, and week 16
Population: Randomized participants who received at least one dose of study drug and with a baseline value and a post-baseline value at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Systolic: week 2 | -0.5 mmHg | Standard Deviation 11.17 |
| Placebo | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Systolic: week 4 | 1.9 mmHg | Standard Deviation 12.29 |
| Placebo | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Systolic: week 16 | 2.2 mmHg | Standard Deviation 13.77 |
| Placebo | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Diastolic: week 2 | -0.1 mmHg | Standard Deviation 7.89 |
| Placebo | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Diastolic: week 4 | 1.3 mmHg | Standard Deviation 7.62 |
| Placebo | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Diastolic: week 16 | 0.8 mmHg | Standard Deviation 8.29 |
| Apremilast 30 mg | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Diastolic: week 4 | -1.0 mmHg | Standard Deviation 9.51 |
| Apremilast 30 mg | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Systolic: week 2 | 0.1 mmHg | Standard Deviation 12.44 |
| Apremilast 30 mg | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Diastolic: week 2 | -0.6 mmHg | Standard Deviation 8.27 |
| Apremilast 30 mg | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Systolic: week 4 | 0.4 mmHg | Standard Deviation 11.88 |
| Apremilast 30 mg | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Diastolic: week 16 | 0.6 mmHg | Standard Deviation 9.12 |
| Apremilast 30 mg | Change From Baseline in Blood Pressure During the Placebo-controlled Period | Systolic: week 16 | 1.0 mmHg | Standard Deviation 12.66 |
Secondary
Change From Baseline in Body Weight at End of Apremilast Extension Period
Time frame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
Population: Randomized participants who received at least 1 dose of apremilast, ie, participants originally randomized to apremilast and participants originally randomized to placebo who entered the apremilast extension phase with at least 1 treatment of apremilast, with a baseline value and at least 1 post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at End of Apremilast Extension Period | -1.20 kg | Standard Deviation 3.802 |
Secondary
Change From Baseline in Body Weight During the Placebo-controlled Period
Time frame: Baseline and week 2, week 4, and week 16
Population: Randomized participants who received at least one dose of study drug and with with a baseline value and a post-baseline value at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight During the Placebo-controlled Period | Week 2 | -0.02 kg | Standard Deviation 1.161 |
| Placebo | Change From Baseline in Body Weight During the Placebo-controlled Period | Week 4 | 0.04 kg | Standard Deviation 1.285 |
| Placebo | Change From Baseline in Body Weight During the Placebo-controlled Period | Week 16 | 0.08 kg | Standard Deviation 2.337 |
| Apremilast 30 mg | Change From Baseline in Body Weight During the Placebo-controlled Period | Week 2 | -0.31 kg | Standard Deviation 1.188 |
| Apremilast 30 mg | Change From Baseline in Body Weight During the Placebo-controlled Period | Week 4 | -0.57 kg | Standard Deviation 2.06 |
| Apremilast 30 mg | Change From Baseline in Body Weight During the Placebo-controlled Period | Week 16 | -0.98 kg | Standard Deviation 2.722 |
Secondary
Change From Baseline in DLQI at Week 16
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life. The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. A negative change from baseline indicates improvement in quality of life.
Time frame: Baseline and week 16
Population: All randomized participants; Missing data at week 16 were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in DLQI at Week 16 | -3.4 score on a scale | Standard Error 0.8 |
| Apremilast 30 mg | Change From Baseline in DLQI at Week 16 | -8.7 score on a scale | Standard Error 0.54 |
p-value: <0.000195% CI: [-7.15, -3.43]ANCOVA
Secondary
Change From Baseline in DLQI at Weeks 32 and 52
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life. The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. A negative change from baseline indicates improvement in quality of life.
Time frame: Baseline, week 32 and week 52
Population: Randomized participants who entered the apremilast extension phase with available data at baseline and each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in DLQI at Weeks 32 and 52 | Week 32 | -9.8 score on a scale | Standard Deviation 8.19 |
| Placebo | Change From Baseline in DLQI at Weeks 32 and 52 | Week 52 | -11.3 score on a scale | Standard Deviation 7.84 |
| Apremilast 30 mg | Change From Baseline in DLQI at Weeks 32 and 52 | Week 32 | -9.9 score on a scale | Standard Deviation 7.28 |
| Apremilast 30 mg | Change From Baseline in DLQI at Weeks 32 and 52 | Week 52 | -11.2 score on a scale | Standard Deviation 7.08 |
Secondary
Change From Baseline in Itch NRS Score at Weeks 32 and 52
The Itch Numeric Rating Scale (NRS) asked participants to assess the worst severity of itch experienced over the past 24 hours on an 11-point scale anchored from 0, representing 'no itching' to 10, representing 'worst itch imaginable'. A negative change from baseline indicates improvement in itch severity.
Time frame: Baseline, week 32 and week 52
Population: Randomized participants who entered the apremilast extension phase with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Itch NRS Score at Weeks 32 and 52 | Week 32 | -3.2 score on a scale | Standard Deviation 3.5 |
| Placebo | Change From Baseline in Itch NRS Score at Weeks 32 and 52 | Week 52 | -3.9 score on a scale | Standard Deviation 3.61 |
| Apremilast 30 mg | Change From Baseline in Itch NRS Score at Weeks 32 and 52 | Week 32 | -2.8 score on a scale | Standard Deviation 3.22 |
| Apremilast 30 mg | Change From Baseline in Itch NRS Score at Weeks 32 and 52 | Week 52 | -3.3 score on a scale | Standard Deviation 3.19 |
Secondary
Change From Baseline in Itch Numeric Rating Scale (NRS) Score at Week 16
The Itch Numeric Rating Scale (NRS) asked participants to assess the worst severity of itch experienced over the past 24 hours on an 11-point scale anchored from 0, representing 'no itching' to 10, representing 'worst itch imaginable'. A negative change from baseline indicates improvement in itch severity.
Time frame: Baseline and week 16
Population: All randomized participants; Missing data at week 16 were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Itch Numeric Rating Scale (NRS) Score at Week 16 | -0.9 score on a scale | Standard Error 0.32 |
| Apremilast 30 mg | Change From Baseline in Itch Numeric Rating Scale (NRS) Score at Week 16 | -2.5 score on a scale | Standard Error 0.21 |
p-value: <0.000195% CI: [-2.34, -0.86]ANCOVA
Secondary
Change From Baseline in Pulse Rate at End of Apremilast Extension Period
Time frame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
Population: Randomized participants who received at least 1 dose of apremilast, ie, participants originally randomized to apremilast and participants originally randomized to placebo who entered the apremilast extension phase with at least 1 treatment of apremilast, with a baseline value and at least 1 post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate at End of Apremilast Extension Period | 1.0 beats/minute | Standard Deviation 10.29 |
Secondary
Change From Baseline in Pulse Rate During the Placebo-controlled Period
Time frame: Baseline and week 2, week 4, and week 16
Population: Randomized participants who received at least one dose of study drug and with a baseline value and a post-baseline value at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate During the Placebo-controlled Period | Week 2 | 0.3 beats/minute | Standard Deviation 10.82 |
| Placebo | Change From Baseline in Pulse Rate During the Placebo-controlled Period | Week 4 | -0.4 beats/minute | Standard Deviation 10.17 |
| Placebo | Change From Baseline in Pulse Rate During the Placebo-controlled Period | Week 16 | 1.0 beats/minute | Standard Deviation 9.97 |
| Apremilast 30 mg | Change From Baseline in Pulse Rate During the Placebo-controlled Period | Week 2 | 3.4 beats/minute | Standard Deviation 9.75 |
| Apremilast 30 mg | Change From Baseline in Pulse Rate During the Placebo-controlled Period | Week 4 | 3.5 beats/minute | Standard Deviation 10.43 |
| Apremilast 30 mg | Change From Baseline in Pulse Rate During the Placebo-controlled Period | Week 16 | 2.0 beats/minute | Standard Deviation 10.99 |
Secondary
Change From Baseline in Skin Discomfort/Pain VAS at Weeks 32 and 52
Participants were asked to indicate their level of skin discomfort/pain in the past week by placing a vertical stroke on a 100 mm horizontal line on which the left-hand boundary (0) represents no skin discomfort/pain, and the right-hand boundary (100) represents worst possible skin discomfort/pain. The distance from the mark to the left-hand boundary was recorded. A negative change from baseline indicates improvement in skin discomfort/pain.
Time frame: Baseline, week 32 and week 52
Population: Randomized participants who entered the apremilast extension phase with available data at baseline and each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Skin Discomfort/Pain VAS at Weeks 32 and 52 | Week 32 | -28.4 score on a scale | Standard Deviation 38.4 |
| Placebo | Change From Baseline in Skin Discomfort/Pain VAS at Weeks 32 and 52 | Week 52 | -35.0 score on a scale | Standard Deviation 36.76 |
| Apremilast 30 mg | Change From Baseline in Skin Discomfort/Pain VAS at Weeks 32 and 52 | Week 32 | -22.6 score on a scale | Standard Deviation 33.71 |
| Apremilast 30 mg | Change From Baseline in Skin Discomfort/Pain VAS at Weeks 32 and 52 | Week 52 | -31.0 score on a scale | Standard Deviation 34.77 |
Secondary
Change From Baseline in Skin Discomfort/Pain Visual Analog Scale (VAS) at Week 16
Participants were asked to indicate their level of skin discomfort/pain in the past week by placing a vertical stroke on a 100 mm horizontal line on which the left-hand boundary (0) represents no skin discomfort/pain, and the right-hand boundary (100) represents worst possible skin discomfort/pain. The distance from the mark to the left-hand boundary was recorded. A negative change from baseline indicates improvement in skin discomfort/pain.
Time frame: Baseline and week 16
Population: All randomized participants; Missing data at week 16 were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Skin Discomfort/Pain Visual Analog Scale (VAS) at Week 16 | -5.4 score on a scale | Standard Error 3.61 |
| Apremilast 30 mg | Change From Baseline in Skin Discomfort/Pain Visual Analog Scale (VAS) at Week 16 | -21.5 score on a scale | Standard Error 2.36 |
p-value: 0.000395% CI: [-24.63, -7.6]ANCOVA
Secondary
Change From Baseline in Waist Circumference at End of Apremilast Extension Period
Time frame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
Population: Baseline and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Waist Circumference at End of Apremilast Extension Period | -0.8 cm | Standard Deviation 4.97 |
Secondary
Change From Baseline in Waist Circumference During the Placebo-controlled Period
Time frame: Baseline and week 2, week 4, and week 16
Population: Randomized participants who received at least one dose of study drug and with a baseline value and a post-baseline value at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Waist Circumference During the Placebo-controlled Period | Week 2 | -0.2 cm | Standard Deviation 3.93 |
| Placebo | Change From Baseline in Waist Circumference During the Placebo-controlled Period | Week 4 | -0.1 cm | Standard Deviation 4.89 |
| Placebo | Change From Baseline in Waist Circumference During the Placebo-controlled Period | Week 16 | 0.1 cm | Standard Deviation 6.16 |
| Apremilast 30 mg | Change From Baseline in Waist Circumference During the Placebo-controlled Period | Week 2 | 0.2 cm | Standard Deviation 3.49 |
| Apremilast 30 mg | Change From Baseline in Waist Circumference During the Placebo-controlled Period | Week 4 | -0.3 cm | Standard Deviation 3.63 |
| Apremilast 30 mg | Change From Baseline in Waist Circumference During the Placebo-controlled Period | Week 16 | -0.9 cm | Standard Deviation 5.06 |
Secondary
Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO) at Week 16: Percentage Work Time Missed
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent of work time missed is derived from the number of hours of work missed due to psoriasis symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 16
Population: All randomized participants with available data and who had reported being employed at baseline and at week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO) at Week 16: Percentage Work Time Missed | -4.1 percent impairment | Standard Error 2.56 |
| Apremilast 30 mg | Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO) at Week 16: Percentage Work Time Missed | -0.9 percent impairment | Standard Error 1.54 |
p-value: 0.266795% CI: [-2.43, 8.73]ANCOVA
Secondary
Change From Baseline in WPAI: PSO at Week 16: Percentage Activity Impairment
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which psoriasis affected their regular daily unpaid activities, measured on a VAS from 1 (no effect on daily activities) to 10 (psoriasis completely prevented daily activities). A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 16
Population: All randomized participants with available data at baseline and at week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WPAI: PSO at Week 16: Percentage Activity Impairment | -13.4 percent impairment | Standard Error 3.66 |
| Apremilast 30 mg | Change From Baseline in WPAI: PSO at Week 16: Percentage Activity Impairment | -21.2 percent impairment | Standard Error 2.24 |
p-value: 0.057295% CI: [-15.9, 0.24]ANCOVA
Secondary
Change From Baseline in WPAI: PSO at Week 16: Percentage Overall Work Impairment
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent overall work impairment takes into account both hours missed due to psoriasis symptoms and the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 16
Population: All randomized participants with available data and who had reported being employed at baseline and at week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WPAI: PSO at Week 16: Percentage Overall Work Impairment | -13.2 percent impairment | Standard Error 4.35 |
| Apremilast 30 mg | Change From Baseline in WPAI: PSO at Week 16: Percentage Overall Work Impairment | -13.8 percent impairment | Standard Error 2.63 |
p-value: 0.892795% CI: [-10.16, 8.86]ANCOVA
Secondary
Change From Baseline in WPAI: PSO at Week 16: Percentage Work Impairment
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent impairment while working was derived from the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 16
Population: All randomized participants with available data and who had reported being employed at baseline and at week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WPAI: PSO at Week 16: Percentage Work Impairment | -11.5 percent impairment | Standard Error 3.82 |
| Apremilast 30 mg | Change From Baseline in WPAI: PSO at Week 16: Percentage Work Impairment | -13.9 percent impairment | Standard Error 2.32 |
p-value: 0.56295% CI: [-10.83, 5.91]ANCOVA
Secondary
Change From Baseline in WPAI: PSO at Week 52: Percentage Activity Impairment
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which psoriasis affected their regular daily unpaid activities, measured on a VAS from 1 (no effect on daily activities) to 10 (psoriasis completely prevented daily activities). A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 52
Population: Randomized participants who entered the apremilast extension phase with available data at baseline and week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WPAI: PSO at Week 52: Percentage Activity Impairment | -32.7 percent impairment | Standard Deviation 33.94 |
| Apremilast 30 mg | Change From Baseline in WPAI: PSO at Week 52: Percentage Activity Impairment | -30.5 percent impairment | Standard Deviation 27.01 |
Secondary
Change From Baseline in WPAI: PSO at Week 52: Percentage Overall Work Impairment
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent overall work impairment takes into account both hours missed due to psoriasis symptoms and the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 52
Population: Randomized participants who entered the apremilast extension phase with available data and who had reported being employed at baseline and at week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WPAI: PSO at Week 52: Percentage Overall Work Impairment | -21.7 percent impairment | Standard Deviation 30.12 |
| Apremilast 30 mg | Change From Baseline in WPAI: PSO at Week 52: Percentage Overall Work Impairment | -25.3 percent impairment | Standard Deviation 29.91 |
Secondary
Change From Baseline in WPAI: PSO at Week 52: Percentage Work Impairment
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent impairment while working was derived from the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 52
Population: Randomized participants who entered the apremilast extension phase with available data and who had reported being employed at baseline and at week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WPAI: PSO at Week 52: Percentage Work Impairment | -21.0 percent impairment | Standard Deviation 29.82 |
| Apremilast 30 mg | Change From Baseline in WPAI: PSO at Week 52: Percentage Work Impairment | -24.4 percent impairment | Standard Deviation 26.78 |
Secondary
Change From Baseline in WPAI: PSO at Week 52: Percentage Work Time Missed
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent of work time missed is derived from the number of hours of work missed due to psoriasis symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed, and a negative change from baseline indicates improvement.
Time frame: Baseline and week 52
Population: Randomized participants who entered the apremilast extension phase with available data and who had reported being employed at baseline and at week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WPAI: PSO at Week 52: Percentage Work Time Missed | -4.6 percent impairment | Standard Deviation 17.43 |
| Apremilast 30 mg | Change From Baseline in WPAI: PSO at Week 52: Percentage Work Time Missed | -3.2 percent impairment | Standard Deviation 17.11 |
Secondary
Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment
Time frame: From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast.
Population: Randomized participants who received at least 1 dose of apremilast, ie, participants originally randomized to apremilast and participants originally randomized to placebo who entered the apremilast extension phase with at least 1 treatment of apremilast, and with at least 1 post-baseline measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Creatinine > 1.7 × ULN | 1 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Glucose < 2.8 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Alanine Aminotransferase > 3 × ULN | 2 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Albumin < 25 g/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Alkaline Phosphatase > 400 U/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Aspartate Aminotransferase > 3 × ULN | 1 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Bilirubin > 1.8 × ULN | 1 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Blood Urea Nitrogen > 15 mmol/L | 2 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Calcium < 1.8 mmol/L | 1 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Calcium > 3.0 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Cholesterol > 7.8 mmol/L | 3 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Glucose > 13.9 mmol/L | 7 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Hemoglobin A1C (Fasting) > 9% | 3 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Lactate Dehydrogenase > 3 × ULN | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Potassium < 3.0 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Potassium > 5.5 mmol/L | 2 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Sodium < 130 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Sodium > 150 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Triglycerides > 3.4 mmol/L | 22 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Hemoglobin: Female < 85 g/L, Male < 105 g/L | 1 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Hemoglobin: Female > 170 g/L, Male > 185 g/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Leukocytes < 1.5 × 10^9/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Lymphocytes < 0.8 × 10^9/L | 3 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Neutrophils, Segmented < 1.0 × 10^9/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Platelets < 75 × 10^9/L | 2 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment | Platelets > 600 × 10^9/L | 0 Participants |
Secondary
Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period
Marked laboratory abnormalities are defined for each parameter below. ULN = upper limit of normal
Time frame: 16 weeks
Population: All randomized participants who received at least one dose of study drug with at least one post-baseline measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Calcium < 1.8 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Albumin < 25 g/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Alkaline Phosphatase > 400 U/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Aspartate Aminotransferase > 3 × ULN | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Bilirubin (umol/L) > 1.8 × ULN | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Blood Urea Nitrogen > 15 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Alanine Aminotransferase > 3 × ULN | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Calcium > 3.0 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Cholesterol > 7.8 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Creatinine > 1.7 × ULN | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Glucose < 2.8 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Glucose > 13.9 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Hemoglobin A1C (Fasting) > 9% | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Lactate Dehydrogenase > 3 × ULN | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Potassium < 3.0 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Potassium > 5.5 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Sodium < 130 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Sodium > 150 mmol/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Triglycerides > 3.4 mmol/L | 6 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Hemoglobin: Female < 85 g/L, Male < 105 g/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Hemoglobin: Female > 170 g/L, Male > 185 g/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Leukocytes < 1.5 × 10^9/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Lymphocytes < 0.8 × 10^9/L | 1 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Neutrophils, Segmented < 1.0 × 10^9/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Platelets < 75 × 10^9/L | 0 Participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Platelets > 600 × 10^9/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Hemoglobin: Female < 85 g/L, Male < 105 g/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Alanine Aminotransferase > 3 × ULN | 2 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Lactate Dehydrogenase > 3 × ULN | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Albumin < 25 g/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Platelets < 75 × 10^9/L | 1 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Alkaline Phosphatase > 400 U/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Potassium < 3.0 mmol/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Aspartate Aminotransferase > 3 × ULN | 1 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Hemoglobin: Female > 170 g/L, Male > 185 g/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Bilirubin (umol/L) > 1.8 × ULN | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Potassium > 5.5 mmol/L | 1 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Blood Urea Nitrogen > 15 mmol/L | 2 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Neutrophils, Segmented < 1.0 × 10^9/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Calcium < 1.8 mmol/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Sodium < 130 mmol/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Calcium > 3.0 mmol/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Leukocytes < 1.5 × 10^9/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Cholesterol > 7.8 mmol/L | 1 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Sodium > 150 mmol/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Creatinine > 1.7 × ULN | 1 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Platelets > 600 × 10^9/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Glucose < 2.8 mmol/L | 0 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Triglycerides > 3.4 mmol/L | 6 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Glucose > 13.9 mmol/L | 3 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Lymphocytes < 0.8 × 10^9/L | 2 Participants |
| Apremilast 30 mg | Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period | Hemoglobin A1C (Fasting) > 9% | 3 Participants |
Secondary
Number of Participants With TEAEs During Apremilast Treatment
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening of a preexisting condition was considered an AE. A serious adverse event (SAE) is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. The Investigator assessed the severity/intensity of each event as mild, moderate, or severe based on level of symptoms.
Time frame: From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast.
Population: All randomized participants who received at least one dose of apremilast, ie, participants originally randomized to apremilast and participants originally randomized to placebo who entered the apremilast extension phase and received at least one dose of apremilast.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | Any TEAE | 217 Participants |
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | Drug-related TEAE | 152 Participants |
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | Severe TEAEs | 14 Participants |
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | Serious TEAEs | 18 Participants |
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | Serious drug-related TEAE | 2 Participants |
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | TEAE leading to drug interruption | 19 Participants |
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | TEAE leading to drug withdrawal | 31 Participants |
| Placebo | Number of Participants With TEAEs During Apremilast Treatment | TEAE leading to death | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening of a preexisting condition was considered an AE. A serious adverse event (SAE) is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. The Investigator assessed the severity/intensity of each event as mild, moderate, or severe based on level of symptoms.
Time frame: From first dose of study drug to week 16 or up to 28 days after last dose for participants who didn't enter the apremilast extension period.
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Any TEAE | 54 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Drug-related TEAE | 26 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Severe TEAEs | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Serious TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Serious drug-related TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | TEAE leading to drug interruption | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | TEAE leading to drug withdrawal | 8 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | TEAE leading to death | 0 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | TEAE leading to death | 0 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Any TEAE | 152 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Serious drug-related TEAE | 1 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Drug-related TEAE | 113 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | TEAE leading to drug withdrawal | 18 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Severe TEAEs | 10 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | TEAE leading to drug interruption | 9 Participants |
| Apremilast 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period | Serious TEAEs | 8 Participants |
Secondary
Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in DLQI at Weeks 32 and 52
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life (QOL). The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL.
Time frame: Baseline, week 32 and week 52
Population: Randomized participants who entered the apremilast extension phase. Missing data were imputed using non-responder imputation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in DLQI at Weeks 32 and 52 | Week 32 | 68.1 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in DLQI at Weeks 32 and 52 | Week 52 | 76.8 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in DLQI at Weeks 32 and 52 | Week 32 | 68.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in DLQI at Weeks 32 and 52 | Week 52 | 79.6 percentage of participants |
Secondary
Percentage of Participants Who Achieved a PASI Score < 3 at Weeks 32 and 52
The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. 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 and the values for each anatomic region are summed to yield the PASI score. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
Time frame: Week 32 and week 52
Population: Randomized participants who entered the apremilast extension phase. Missing data were imputed using non-responder imputation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a PASI Score < 3 at Weeks 32 and 52 | Week 32 | 58.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a PASI Score < 3 at Weeks 32 and 52 | Week 52 | 50.7 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a PASI Score < 3 at Weeks 32 and 52 | Week 52 | 37.5 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a PASI Score < 3 at Weeks 32 and 52 | Week 32 | 40.1 percentage of participants |
Secondary
Percentage of Participants Who Achieved a Patient Benefit Index (PBI) Global Score of ≥ 1 at Week 16
The PBI is a validated patient-reported instrument to assess patient-relevant benefits of psoriasis treatment. Prior to starting study treatment, participants were asked to assess the importance of a series of treatment goals (from not important to very important) by completing the Patient Needs Questionnaire (PNQ). After a period of treatment (16 weeks), participants were then asked to assess the extent to which these goals were achieved (from not at all to very) by completing the Patient Benefit Questionnaire (PBQ). The Patient Benefit Index represents the benefits realized as a function of most important needs. The PBI score ranges from 0 (no benefit) to 4 (maximum benefit).
Time frame: Week 16
Population: All randomized participants; Missing data at week 16 were imputed using multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Patient Benefit Index (PBI) Global Score of ≥ 1 at Week 16 | 39.9 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a Patient Benefit Index (PBI) Global Score of ≥ 1 at Week 16 | 76.6 percentage of participants |
p-value: <0.000195% CI: [24.1, 49.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a PBI Score of ≥ 1 at Weeks 32 and 52
The PBI is a validated patient-reported instrument to assess patient-relevant benefits of psoriasis treatment. Prior to starting study treatment, participants were asked to assess the importance of a series of treatment goals (from not important to very important) by completing the Patient Needs Questionnaire (PNQ). After a period of treatment (32 weeks and 52 weeks), participants were then asked to assess the extent to which these goals were achieved (from not at all to very) by completing the Patient Benefit Questionnaire (PBQ). The Patient Benefit Index represents the benefits realized as a function of most important needs. The PBI score ranges from 0 (no benefit) to 4 (maximum benefit).
Time frame: Week 32 and week 52
Population: Randomized participants who entered the apremilast extension phase. Missing data were imputed using non-responder imputation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a PBI Score of ≥ 1 at Weeks 32 and 52 | Week 32 | 66.7 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a PBI Score of ≥ 1 at Weeks 32 and 52 | Week 52 | 65.2 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a PBI Score of ≥ 1 at Weeks 32 and 52 | Week 32 | 67.8 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a PBI Score of ≥ 1 at Weeks 32 and 52 | Week 52 | 63.8 percentage of participants |
Secondary
Percentage of Participants Who Achieved a Psoriasis Area Severity Index (PASI) Score < 3 at Week 16
The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. 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 and the values for each anatomic region are summed to yield the PASI score. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
Time frame: Week 16
Population: All randomized participants; missing data at week 16 were imputed using multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Psoriasis Area Severity Index (PASI) Score < 3 at Week 16 | 26.3 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a Psoriasis Area Severity Index (PASI) Score < 3 at Week 16 | 39.7 percentage of participants |
p-value: 0.032895% CI: [1.1, 25.8]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16
Body surface area is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA.
Time frame: Baseline and week 16
Population: All randomized participants; Missing data at week 16 were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16 | 18.5 percent change | Standard Error 12.95 |
| Apremilast 30 mg | Percent Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16 | -19.8 percent change | Standard Error 6.58 |
p-value: 0.008595% CI: [-66.58, -10.14]ANCOVA
Secondary
Percent Change From Baseline in BSA Affected by Psoriasis at Weeks 32 and 52
Body surface area is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA.
Time frame: Baseline, week 32 and week 52
Population: Randomized participants who entered the apremilast extension phase with available data at baseline and each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in BSA Affected by Psoriasis at Weeks 32 and 52 | Week 32 | -49.5 percent change | Standard Deviation 47.35 |
| Placebo | Percent Change From Baseline in BSA Affected by Psoriasis at Weeks 32 and 52 | Week 52 | -49.9 percent change | Standard Deviation 53.25 |
| Apremilast 30 mg | Percent Change From Baseline in BSA Affected by Psoriasis at Weeks 32 and 52 | Week 52 | -32.0 percent change | Standard Deviation 93.09 |
| Apremilast 30 mg | Percent Change From Baseline in BSA Affected by Psoriasis at Weeks 32 and 52 | Week 32 | -40.2 percent change | Standard Deviation 51.79 |
Secondary
Percent Change From Baseline in EQ-5D Index Score at Week 16
EQ-5D measures the participants general health state as a vertical VAS and 5 quality of life domains: mobility, self-care, main activity (work, study, housework, family/leisure activities), pain/discomfort, and anxiety/depression. Each dimension is rated on three levels (no problems, some/moderate problems, extreme problems). An EQ-5D summary index is derived by applying a formula that attaches values (weights) to each of the levels in each dimension. EQ-5D index values were derived using the UK scoring algorithm, where a higher score indicates a better health state. The range of the score is from -0.224 to 1, with 0 corresponding to death, 1 corresponding to full health, and negative numbers indicate health states worse than death. A positive change from baseline indicates improvement.
Time frame: Baseline and week 16
Population: All randomized participants with available data at baseline and week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in EQ-5D Index Score at Week 16 | 165.9 percent change | Standard Error 89.8 |
| Apremilast 30 mg | Percent Change From Baseline in EQ-5D Index Score at Week 16 | 17.8 percent change | Standard Error 59.59 |
p-value: 0.155995% CI: [-352.8793, 56.8304]ANCOVA
Secondary
Percent Change From Baseline in EQ-5D Index Score at Week 52
EQ-5D measures the participants general health state as a vertical VAS and 5 quality of life domains: mobility, self-care, main activity (work, study, housework, family/leisure activities), pain/discomfort, and anxiety/depression. Each dimension is rated on three levels (no problems, some/moderate problems, extreme problems). An EQ-5D summary index is derived by applying a formula that attaches values (weights) to each of the levels in each dimension. EQ-5D index values were derived using the UK scoring algorithm, where a higher score indicates a better health state. The range of the score is from -0.224 to 1, with 0 corresponding to death, 1 corresponding to full health, and negative numbers indicate health states worse than death. A positive change from baseline indicates improvement.
Time frame: Baseline and week 52
Population: Randomized participants who entered the apremilast extension phase with available data at baseline and week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in EQ-5D Index Score at Week 52 | 214.103 percent change | Standard Deviation 1799.6328 |
| Apremilast 30 mg | Percent Change From Baseline in EQ-5D Index Score at Week 52 | 11.039 percent change | Standard Deviation 224.3001 |
Secondary
Percent Change From Baseline in EQ-5D VAS Score at Week 52
EQ-5D measures the participant's general health state on a vertical VAS and five quality of life domains. The EQ-5D VAS score ranges from 0 to 100, where a score of 0 indicates the worst imaginable health states and a score of 100 indicates the best imaginable health state. A positive change from baseline indicates improvement.
Time frame: Baseline and week 52
Population: Randomized participants who entered the apremilast extension phase with available data at baseline and week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in EQ-5D VAS Score at Week 52 | 51.4 percent change | Standard Deviation 132.13 |
| Apremilast 30 mg | Percent Change From Baseline in EQ-5D VAS Score at Week 52 | 33.6 percent change | Standard Deviation 78.53 |
Secondary
Percent Change From Baseline in European Quality of Life 5-Dimension (EQ-5D) VAS Score at Week 16
EQ-5D measures the participant's general health state on a vertical VAS and five quality of life domains. The EQ-5D VAS score ranges from 0 to 100, where a score of 0 indicates the worst imaginable health states and a score of 100 indicates the best imaginable health state. A positive change from baseline indicates improvement.
Time frame: Baseline and week 16
Population: All randomized participants with available data at baseline and week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in European Quality of Life 5-Dimension (EQ-5D) VAS Score at Week 16 | 18.9 percent change | Standard Error 15.96 |
| Apremilast 30 mg | Percent Change From Baseline in European Quality of Life 5-Dimension (EQ-5D) VAS Score at Week 16 | 33.8 percent change | Standard Error 10.67 |
p-value: 0.421695% CI: [-21.62, 51.48]ANCOVA