Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

A PPPASI 50 response is defined as a ≥ 50% reduction in PPPASI total score from baseline. The PPPASI is a system used for assessing and grading the severity (in terms of erythema, pustules/vesicle and desquamation/scale) and area of PPP lesions and their response to therapy. The PPPASI produces a numeric score that can range from 0 to 72, with a higher score indicating more severe disease. Participants who discontinued investigational product before week 16 due to lack of efficacy, adverse event, or use of protocol-prohibited medication (intercurrent events) were to be considered as treatment failures as the result of the intercurrent event and the PPPASI-50 values for visits on and after the intercurrent event were imputed as non-responders. The missing PPPASI-50 values due to the other reasons were imputed using the multiple imputation method.

Time frame: Baseline and Week 16

Population: ITT Population: Included all randomized participants.

The DLQI is a skin disease-specific Quality of Life (QoL) questionnaire comprised of 10 items assessing the participant's status over the previous week. The DLQI was used to assess 6 different aspects that may affect QoL: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. The DLQI produces a numeric score ranging from 0 to 30, with a higher score indicating more severe disease. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of IE (investigational product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Time frame: Baseline and Week 16

Population: ITT Population: Included all randomized participants. Only participants with observed data, including participants who had intercurrent events and were assigned baseline values were included.

The PPSI is a system used for assessing and grading the severity of PPP lesions and their response to therapy. Evaluation of skin lesion site are assessed separately for erythema, pustules/vesicle and desquamation/scale, where each are rated on a scale of 0 to 4 and summed to produce a numeric total score than can range from 0 to 12, with a higher score indicating more severe disease. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of IE (investigational product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Time frame: Baseline and Week 16

Population: ITT Population: Included all randomized participants. Only participants with observed data, including participants who had intercurrent events and were assigned baseline values were included.

The PPPASI is a system used for assessing and grading the severity (in terms of erythema, pustules/vesicle and desquamation/scale) and area of PPP lesions and their response to therapy. The PPPASI produces a numeric score that can range from 0 to 72, with a higher score indicating more severe disease. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of intercurrent event (IE) (investigational product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the mixed-effects model for repeated measures (MMRM) application.

Time frame: Baseline and Week 16

Population: ITT Population: Included all randomized participants. Only participants with observed data, including participants who had intercurrent events and were assigned baseline values were included.

Participants assessed the degree of pain/discomfort symptoms on palms and soles caused by PPP on a VAS. The VAS score ranged from 0 to 100. The left-hand boundary (0) on the VAS represents no pain/discomfort and the right-hand boundary (100) represents pain/discomfort as severe as can be imagined by the participant. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of IE (investigational product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Time frame: Baseline and Week 16

Population: ITT Population: Included all randomized participants. Only participants with observed data, including participants who had intercurrent events and were assigned baseline values were included.

Participants assessed the degree of pruritus itching symptoms on palms and soles caused by PPP on a VAS. The VAS score ranged from 0 to 100. The left-hand boundary (0) on the VAS represents no itch and the right-hand boundary (100) represents itch as severe as can be imagined by the participant. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of IE (investigational product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Time frame: Baseline and Week 16

Population: ITT Population: Included all randomized participants. Only participants with observed data, including participants who had intercurrent events and were assigned baseline values were included.

TEAEs were defined as any untoward medical occurrence in a participant irrespective of a causal relationship with the study treatment that began or worsened on or after the first dose of study treatment. A serious TEAE met at least 1 of the following criteria: * Resulted in death. * Was immediately life-threatening. * Required in-patient hospitalization or prolongation of existing hospitalization. * Resulted in persistent or significant disability/incapacity. * Was a congenital anomaly/birth defect. * Was any other medically important serious event. TEAEs of interest were defined as any of the following: * Depression. * Serious infection. * Risk of triggering suicide. * Serious diarrhea, nausea and vomiting. * Malignancies. * Vasculitis and Vasculopathy. * Serious Hypersensitivity. * Weight change (weight decrease). Clinically significant changes in body weight, vital signs and laboratory abnormalities were also recorded as TEAEs.

Time frame: Placebo-controlled period: Day 1 to Week 16; Apremilast exposure period : Apremilast Day 1 to a maximum of Week 52 (plus 4 weeks safety follow-up)

Population: Safety Population: Included all randomized participants who received at least 1 dose of investigational product.