Clinical trial NCT01245140: Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis
Official title: Efficacy of Oral Alitretinoin Treatment in Patients With Palmo-plantar Pustulosis (PPP) Inadequately Responding to Standard Topical Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Keywords: Palmo-Plantar Pustolosis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica
First posted: 2010-11-22
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Palmo-plantar pustulosis (PPP) is an inflammatory skin disease affecting palms and soles. The disease is considered as a sub-form of psoriasis and presents with sterile pustules of the palms and the soles. This study investigates the efficacy of alitretinoin in patients who have not responded to topical drugs (e.g., steroid creams), who are suffering for at least 6 month from the condition and whose disease severity is confirmed by a score.

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

Primary outcomes:
measure: Change From Baseline in the Palmo-plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) Score at the End of Treatment (EOT) (Week 24) or at the Last Assessment
timeFrame: Baseline and EOT (Week 24) or the last assessment
measure: Number of Participants With PPPASI 50 Response and PPPASI 75 Response
timeFrame: From Baseline until EOT (Week 24) or the last assessment
Secondary outcomes:
measure: Total Pustule Count at Baseline; Weeks 4, 8, 12, 16, and 20; and at EOT (Week 24)
timeFrame: Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24)
measure: Absolute Change From Baseline (BL) in Total Pustule Count at Weeks 4, 8, 12, 16, and 20 and at EOT (Week 24)
timeFrame: Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24)
measure: Mean Modified Psoriasis Area Severity Index (mPASI) Score at Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24)
timeFrame: Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24)
measure: Change From Baseline in the mPASI Score at EOT (Week 24) or at the Last Assessment
timeFrame: Baseline and EOT (Week 24) or the last assessment
measure: Number of Participants With mPASI 50 Response and mPASI 75 Response
timeFrame: From Baseline until EOT (Week 24)
measure: Mean Nail Psoriasis Severity Index (NAPSI) Score for Nail Bed Psoriasis and Nail Matrix Psoriasis at Baseline, Week 12, and EOT (Week 24)
timeFrame: Baseline, Week 12, and EOT (Week 24)
measure: Absolute Change From Baseline in NAPSI Score for Nail Bed Psoriasis and Nail Matrix Psoriasis at Week 12, and EOT (Week 24)
timeFrame: Baseline, Week 12, and EOT (Week 24)
measure: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) and an AE/SAE Related to Study Treatment
timeFrame: From Baseline until safety follow up (Week 29)
measure: Absolute Change From Baseline in Fasted Lipid Laboratory Test Values at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and at Safety Follow-up (Week 29)
timeFrame: Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29)
measure: Absolute Change From Baseline in Fasted LDL/HDL Ratio at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and at Safety Follow-up (Week 29)
timeFrame: Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24) and safety follow-up (Week 29)
measure: Number of Participants With the Indicated Shift in the Indicated Laboratory Values From Baseline (BL) to EOT (Week 24)
timeFrame: From Baseline until EOT (Week 24)
measure: Mean Center for Epidemiological Studies Depression Scale (CES-D) Scores at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)
timeFrame: Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29)
measure: Absolute Change From Baseline (BL) in CES-D Scores at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)
timeFrame: Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29)
measure: Mean Columbia Suicide Severity Rating Scale (CSSRS) Scores at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)
timeFrame: Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24), and safety follow-up (Week 29)
measure: Absolute Change From Baseline in the CSSRS Score at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)
timeFrame: Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29)
measure: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Screening, Baseline, and EOT (Week 24)
timeFrame: Screening, Baseline, and EOT (Week 24)
measure: Mean Heart Rate (HR) at Baseline, Screening, and EOT (Week 24)
timeFrame: Screening, Baseline, and EOT (Week 24)
measure: Mean Body Weight at Screening, Baseline ,and EOT (Week 24)
timeFrame: Screening, Baseline, and EOT (Week 24)
measure: Change From Baseline in SBP and DBP at EOT (Week 24)
timeFrame: Baseline and EOT (Week 24)
measure: Change From Baseline in Heart Rate at EOT (Week 24)
timeFrame: Baseline and EOT (Week 24)
measure: Change From Baseline in Weight at EOT (Week 24)
timeFrame: Baseline and EOT (Week 24)
measure: Number of Participants With Normal/Abnormal Physical Status at Baseline With a Worst Post-Baseline Finding of Normal/Abnormal
timeFrame: Baseline and EOT (Week 24)
measure: Number of Participants With a Negative Serum Pregnancy Test at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)
timeFrame: Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); safety follow-up (Week 29)
Other outcomes:
Locations:
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Witten
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: