Fluphenazine Decanoate for Psoriasis
We are doing this research study to evaluate the effectiveness and safety of fluphenazine decanoate when injected with a needle into psoriasis lesions in adults. Fluphenazine decanoate is FDA (U.S. Food and Drug Administration) approved for use in people who have schizophrenia and psychotic symptoms. Fluphenazine decanoate is not approved by the FDA for use in psoriasis. Fluphenazine decanoate slows T cell growth in cells in laboratory test tubes. Its usefulness and safety in people with psoriasis will be investigated in this study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Ascending-Dose, Double-Blind, Placebo-Controlled, Bilateral Study of Intralesional Fluphenazine Decanoate in Psoriasis|
- Change in Target Lesion Score at Week 4 Compared to Baseline [ Time Frame: Baseline to week 4 ] [ Designated as safety issue: No ]Change in score from 0-14 of target lesion disease activity based on scaling, erythema, and induration as determined by a physician assessor at week 4 compared to baseline (with 0 being no disease activity and 14 being maximum disease activity).
- Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline. [ Time Frame: Baseline to week 4 ] [ Designated as safety issue: No ]Target lesion pruritus as measured by the Visual Analog Scale (VAS) from 0 to 100 mm at week 4 compared to baseline (with 0 being no pruritis and 100 being maximum pruritis).
|Study Start Date:||July 2006|
|Study Completion Date:||September 2008|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
Experimental: Fluphenazine treated
Treated with fluphenazine
Drug: Fluphenazine Decanoate
Fluphenazine decanoate marketed by APP Pharmaceuticals (25 mg/mL, 5 mL vial) was used in this study. This was an ascending dose study with the first cohort of 5 subjects dosed at 10 µg/mL, followed by 5 subject dosed in the second cohort at 100 µg/mL. Note: "APP Pharmaceuticals" is the name of the pharmaceutical company; APP is not an acronym.
Placebo Comparator: Placebo
Treated with Placebo
The sterile placebo (sesame oil with 1.2% (w/v) benzyl alcohol) was prepared at the University of Iowa, Division of Pharmaceutical Services, a FDA registered pharmaceutical manufacturing facility.
Psoriasis is a hyperproliferative, inflammatory, immune-mediated skin disease that affects approximately 2% of the United States and European populations (Tutrone 2001, Kipnis 2005). This disease manifests as red, scaly plaques that are itchy and/or painful. Patients with psoriasis may be socially stigmatized because of their appearance. Currently, there is no cure for this condition. Often, repeated medical treatments are necessary and can become expensive. Treatment with topical corticosteroids is the mainstay therapy for mild to moderate psoriasis. In more severe cases, systemic therapies (e.g., cyclosporine) and phototherapy (e.g., ultraviolet B (UVB) irradiation) are used. These treatments, however, are associated with toxicities or inconvenience. There is anecdotal evidence to suggest that antipsychotic drugs have a beneficial effect on psoriasis (Gupta 2001, 2003).
Fluphenazine is a phenothiazine antipsychotic drug. In vitro, fluphenazine kills activated human T cells under conditions that do not affect resting T cells (Immune Control Inc. data not shown). To determine the size of a therapeutic window for human peripheral blood mononuclear cells (PBMC)s, Immune Control Inc. performed the following experiments. First, phytohemagglutinin- (PHA)-activated cells were exposed to 2, 10, or 20 µM fluphenazine for 0, 18, 24, 36, 48, or 72 hours. Second, resting cells were exposed to identical fluphenazine concentrations for identical time periods, after which the drug was washed out of the cells, and the cells activated with PHA. In all cases, deoxyribonucleic acid (DNA) synthesis was measured by exposing the cells to tritiated thymidine, and measuring the incorporated nucleotide by scintillation counting. The data show that exposure of activated cells to 10 µM fluphenazine for 72 hours, or 20 µM fluphenazine for 36 hours, caused the death of virtually all of the activated cells. The ability of the resting cells to initiate DNA synthesis after activation, by contrast, was largely unaffected by these fluphenazine exposures. Although we cannot precisely control intralesional fluphenazine concentrations, we expect that injections of up to 1 mg fluphenazine decanoate will yield local concentrations that exceed 10 µM without significant systemic fluphenazine concentrations.
We propose that fluphenazine will suppress proliferating T-lymphocytes in psoriatic plaques in vivo and thus result in healing of plaques. The objective of this study is to assess the safety and biologic activity of intralesional injection of fluphenazine decanoate in adult subjects with psoriasis.
|United States, Massachusetts|
|Tufts-New England Medical Center|
|Boston, Massachusetts, United States, 02111|
|Principal Investigator:||Alice B Gottlieb, MD, PhD||Tufts Medical Center|