Efficacy of oral alitretinoin treatment in patients with palmo-plantar pustulosis (PPP) inadequately responding to standard topical treatment

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Male patients, or female patients if post-menopausal as defined in protocol section 7.4.1., or hysterectomized, or bilaterally ovarectomized, or if pre-menopausal and willing to use at least 1 but preferably 2 methods of contraception under supervision of the investigator or a gynecologist
2. Aged 18 to 75 years
3. Patients with PPP for at least 6 months, with or without psoriasis lesions on other areas of the skin
4. A PPPASI score of at least 8 with involvement of at least 10% of the palms and/or the soles
5. Refractory to standard topical therapy
6. Written informed consent provided

Exclusion Criteria

1. Patients unable to comply with the requirements of the study
2. Female patients who are pregnant or who plan to become pregnant or who are breast feeding
3. Female patients of childbearing potential who cannot use or will not commit to using at least one but preferably two effective forms of contraception simultaneously under supervision of the investigator or a gynecologist
4. Patients whose disease is adequately controlled by standard non-medicated therapy (skin moisturizing and protection) and standard topical corticosteroid therapy, but whose disease has relapsed following discontinuation of these treatments
5. Patients with known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component, especially soybean oil and partly hydrogenated soybean oil
6. Patients treated with any of the following treatments 4 weeks before the start of study treatment:
a. systemic drugs: corticosteroids, immunosuppressants, methotrexate
b. phototherapy: ultraviolet B light therapy [UVB], Psoralen with ultraviolet A combination therapy [PUVA], Grenz rays, X-rays
7. Patients treated with biologic treatments within 12 weeks prior to start of study treatment.
8. Patients treated with any systemic or topical retinoids within 1 year or 1 month, respectively, before start of study treatment, and patients who received systemic retinoids for treatment for PPP at any time
9. Patients with severe generalized pustular psoriasis
10. Patient has a skin condition of palms and/or soles which is assessed as unrelated to PPP by the investigator
11. Patients with any serious medical condition which, in the opinion of the investigator, may interfere with the safety of the patient
12. Patients with hepatic insufficiency, severe renal failure, uncontrolled hypercholesterinemia, uncontrolled as characterized by:
a. AST/ ALT > 2,5 x ULN
b. Creatinine clearance <60ml/min (calculated, Cockcroft-Gault)
c. Fasting triglyceridemia > 1.5 x ULN
d. Fasting cholesterol > 1.5 x ULN
e. Fasting LDL cholesterol > 1.5x ULN
13. Patients with hypothyroidism as indicated by TSH/T4 test <0.9 x LLN or hypervitaminosis A
14. Patients with cardiovascular risk factors that would exclude a starting dose of 30 mg of alitretinoin
15. Patients 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
16. Patients included in the study of an investigational drug within 2 months before start of study treatment (3 months for biologics)
17. Patients with a score of 20 or more on CES-D, or with active major psychiatric disorder (e.g. Major Depressive Disorder, Generalized Anxiety Disorder, Bipolar Disorder (I or II), or schizophrenia)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Percentage change in PPPASI</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Efficacy<br /><br>- PPPASI 50 response and PPPASI 75 response defined as a 50% and 75% decrease<br /><br>in PPPASI from baseline, respectively.<br /><br>- Value and change in pustule count on palms and soles to assess the response<br /><br>with regard to pustular lesions<br /><br>- Value and percentage change in mPASI, mPASI 50 response, and mPASI 75 response<br /><br>- Value and change in NAPSI<br /><br><br /><br>Safety<br /><br>- Overall incidence and severity of AEs<br /><br>- Laboratory test results (fasted lipid tests) and incidence of abnormal<br /><br>laboratory values<br /><br>- Value and change in CES D</p><br>