Intervention: Tretinoin
Trial phase: Phase 2
ATC code: D10AD01 | D10AD04 | D10AD51 | D10AD54 | D10BA01 | D11AH04 | L01XF01 | L01XF02
SMILES: CC(C=CC1=C(C)CCCC1(C)C)=CC=CC(C)=CC(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 24
Group description: Participants received an alitretinoin 30 mg capsule orally QD for up to 24 weeks.
Eligibility criteria:
Inclusion Criteria:

A female subject is eligible to participate if she is of:

Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea and a follicle stimulating hormone concentration of ≥40 international units (IU)/L.
Child-bearing potential with negative pregnancy test as determined by human chorionic gonadotropin (hCG) test at screening or prior to dosing and either 1) agrees to use a medically acceptable contraception method for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point and continue contraception until the end of the study, or 2) has only same-sex partners, when this is her preferred and usual lifestyle.
Capable of understanding and willing to provide signed and dated written voluntary informed consent (and any local or national authorization requirements) before any protocol specific procedures are performed.
Male or female aged at least 18 years at time of consent and at time of first dose.
Have PPP for at least 6 months, with or without psoriasis lesions on other areas of the skin
A PPPASI score of at least 8 with involvement of at least 10% of the palms and/or the soles
Refractory to standard topical corticosteroid therapy

Exclusion Criteria:

Unable to comply with the requirement of the study
Female subjects who are pregnant or who plan to become pregnant or who are breast feeding
Subjects whose disease is adequately controlled by standard non-medicated therapy (skin moisturizing and protection)
Known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component, especially soybean oil and partly hydrogenated soybean oil

Treated with any of the following treatments 4 weeks before the start of study treatment:

systemic drugs: corticosteroids, immunosuppressants, methotrexate
phototherapy: ultraviolet B light therapy [UVB], psoralen with ultraviolet A combination therapy [PUVA], Grenz rays, X-rays
Treated with biologic treatments within 6 weeks prior to start of study treatment.
Abnormal hematology
Treated with any systemic or topical retinoids within 3 months or 1 month, respectively, before start of study treatment
Treated with high-potency topical corticosteroids within 2 weeks before the start of study treatment
Severe generalized pustular psoriasis
A skin condition of palms and/or soles that interferes with the diagnosis of PPP by the investigator
Any condition that, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study.

Hepatic insufficiency, severe renal failure, uncontrolled hypercholesterolemia as characterized by:

AST/ ALT >2.5 x upper limit of normal (ULN)
Creatinine clearance <60 mL/min (calculated, Cockcroft-Gault)
Fasting triglyceridemia >1.5 x upper limit of normal (ULN)
Fasting cholesterol >1.5 x ULN
Fasting low-density lipoprotein (LDL) cholesterol >1.5x ULN
Subjects with hypothyroidism as indicated by thyroid stimulating hormone (TSH) above ULN and thyroxine (T4) test below LLN or hypervitaminosis A

Subjects with unstable cardiac disease or poorly controlled cardiovascular risk factors, for example:

Acute coronary syndrome or coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass graft [CABG]) within 3 months before start of study treatment
Poorly controlled diabetes mellitus (HbA1c >8.5%)
Systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg at the screening examination
Subjects receiving drugs with a potential for drug-drug interaction, such as systemic tetracyclines, ketoconazole, or St. John's Wort within 1 week, or receiving systemic itraconazole within 2 weeks, before start of study treatment
Subjects included in the study of an investigational drug within 2 months before start of study treatment (3 months for biologics)
Subjects with a score of 20 or more on the Center for Epidemiologic Studies Depression scale (CES-D), or with active major psychiatric disorder (eg, Major Depressive Disorder, Generalized Anxiety Disorder, Bipolar Disorder [I or II], or schizophrenia)
Subjects who score a 4 or 5 for the previous 30 days on the Columbia Suicide Severity Rating Scale (CSSRS) at Screening or Baseline
Subjects who have made a suicide attempt within the 6 months preceding the Screening or Baseline visits