Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: alitretinoin; Placebo
Intervention description: to receive verum (20 patients); to receive placebo (10 patients)
Intervention MeSH terms: Alitretinoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Palmo-Plantar Pustolosis

Summary:

      The main purpose of this study is to demonstrate the improvement in the skin condition rate
      of patients receiving alitretinoin compared to patients receiving placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. Male or female aged at least 18 years at time of consent and at time of first dose.

          4. Have PPP for at least 6 months, with or without psoriasis lesions on other areas of
             the skin

          5. A PPPASI score of at least 8 with involvement of at least 10% of the palms and/or the
             soles

          6. Refractory to standard topical corticosteroid therapy

        Exclusion Criteria:

          1. Unable to comply with the requirement of the study

          2. Female subjects who are pregnant or who plan to become pregnant or who are breast
             feeding

          3. Subjects whose disease is adequately controlled by standard non-medicated therapy
             (skin moisturizing and protection)

          4. Known hypersensitivity to other retinoids or vitamin A derivatives, or to any study
             medication component, especially soybean oil and partly hydrogenated soybean oil

          5. 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

          6. Treated with biologic treatments within 6 weeks prior to start of study treatment.

          7. Abnormal hematology

          8. Treated with any systemic or topical retinoids within 3 months or 1 month,
             respectively, before start of study treatment

          9. Treated with high-potency topical corticosteroids within 2 weeks before the start of
             study treatment

         10. Severe generalized pustular psoriasis

         11. A skin condition of palms and/or soles that interferes with the diagnosis of PPP by
             the investigator

         12. Any condition that, in the judgment of the investigator, would put the subject at
             unacceptable risk for participation in the study.

         13. 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

         14. Subjects with hypothyroidism as indicated by thyroid stimulating hormone (TSH) above
             ULN and thyroxine (T4) test below LLN or hypervitaminosis A

         15. 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%)

         16. Systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg at the
             screening examination

         17. 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

         18. Subjects included in the study of an investigational drug within 2 months before start
             of study treatment (3 months for biologics)

         19. 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)

         20. Subjects who score a 4 or 5 for the previous 30 days on the Columbia Suicide Severity
             Rating Scale (CSSRS) at Screening or Baseline

         21. Subjects who have made a suicide attempt within the 6 months preceding the Screening
             or Baseline visits