Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica
Information provided by (Responsible Party):
GlaxoSmithKline ( Stiefel, a GSK Company )
ClinicalTrials.gov Identifier:
NCT01245140
First received: November 16, 2010
Last updated: September 11, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Psoriasis
Drug: alitretinoin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Oral Alitretinoin Treatment in Patients With Palmo-plantar Pustulosis (PPP) Inadequately Responding to Standard Topical Treatment

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Palmo-Plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) [ Time Frame: 24 weeks (End of Treatment) ] [ Designated as safety issue: No ]
    Scores for PPPASI will be obtained during screening, at baseline, at each visit during the treatment period and at EoT visit.


Secondary Outcome Measures:
  • To assess the response of pustular lesions to total pustule count [ Time Frame: Day 1 to week 24 ] [ Designated as safety issue: No ]
    Pustule count will be performed at baseline, during treatment period and at EoT visit.

  • To assess the response to psoriasis lesions in locations other than the hands to the treatment [ Time Frame: Day 1 to week 24 ] [ Designated as safety issue: No ]
    mPASI

  • To assess the response of nail involvement to the treatment [ Time Frame: Day 1, week 12 and week 24 ] [ Designated as safety issue: No ]
    NAPSI Scores will be taken for finger nails only. No scores will be taken for patients with traumatic or fungal changes in nails (confirmed by KOH-test).

  • Safety [ Time Frame: Screening to End-of-study ] [ Designated as safety issue: Yes ]
    The investigator will evaluate safety in accordance with the Schedule of Assessments, by AE monitoring, laboratory tests (fasted lipid tests), physical examination, pregnancy testing for female patients of child bearing potential and the CES-D questionnaire.


Enrollment: 33
Study Start Date: April 2011
Study Completion Date: April 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active
to receive study drug (alitretinoin, 20 patients)
Drug: alitretinoin
to receive verum (20 patients)
Other Name: Toctino
Placebo Comparator: Placebo
to receive placebo (dummy drug, 10 patients)
Drug: Placebo
to receive placebo (10 patients)
Other Name: 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01245140

Locations
France
GSK Investigational Site
Paris Cedex 10, France, 75475
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 80337
GSK Investigational Site
Witten, Nordrhein-Westfalen, Germany, 58453
GSK Investigational Site
Berlin, Germany, 10827
GSK Investigational Site
Berlin, Germany, 10117
GSK Investigational Site
Hamburg, Germany, 20354
Netherlands
GSK Investigational Site
Nijmegen, Netherlands, 6525 GA
United Kingdom
GSK Investigational Site
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
Stiefel, a GSK Company
Basilea Pharmaceutica
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline ( Stiefel, a GSK Company )
ClinicalTrials.gov Identifier: NCT01245140     History of Changes
Other Study ID Numbers: 117221, 2010-022843-39, BAP02028
Study First Received: November 16, 2010
Last Updated: September 11, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by GlaxoSmithKline:
Palmo-Plantar Pustolosis

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Alitretinoin
Tretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on September 22, 2014