Clinical trial NCT00929578: Fluphenazine Hydrochloride for Psoriasis
Official title: Ascending-Dose, Double-Blind, Placebo-Controlled, Study of Intralesional Fluphenazine Hydrochloride for Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Keywords: Psoriasis
T-lymphocytes
Fluphenazine
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: Immune Control
First posted: 2009-06-29
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the safety and biologic activity of intralesional injection of fluphenazine in adult subjects with psoriasis.

Detailed description: This is a double-blind, placebo-controlled, bilateral, ascending dose study.

In vitro, fluphenazine has been shown to suppress growth of proliferating T-lymphocytes. Fluphenazine would be expected to also suppress growth of proliferating T-lymphocytes in psoriatic plaques.

Eligibility criteria: Inclusion Criteria:

* Adults 18 to 65 years of age with psoriasis, in general good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, and physical examination
* Must have symmetric target lesions 2-4 cm in diameter on each side of the body (e.g., thighs) with baseline Target Lesion Score (TLS) of 6 or higher (scale of 0-12) for each target
* Women are eligible to participate in the study if they meet one of the following criteria:

  * Women who are postmenopausal (for at least one year), sterile, or hysterectomized
  * Women of childbearing potential must undergo monthly pregnancy testing during the study and agree to use two of the following methods of contraception throughout the study and for 60 days after the last dose of study drug:

    * Oral contraceptives
    * Transdermal contraceptives
    * Injectable or implantable methods
    * Intrauterine devices
    * Barrier methods (diaphragm with spermicide, condom with spermicide)

(Abstinence and Tubal Ligation are also considered a form of Birth control.)

Exclusion Criteria:

* Patient is not asymptomatic and has major ailments on screening exam.
* Infliximab (Remicade®) or alefacept (Amevive®) within the past 6 months (24 weeks)
* Etanercept (Enbrel®), efalizumab (Raptiva™), adalimumab (Humira®) or other tumor necrosis factor (TNF)-alpha inhibitor within the past 3 months (12 weeks)
* Other systemic psoriasis therapies (e.g., methotrexate, cyclosporine, acitretin) or oral psoralen with ultraviolet A (PUVA) within the past 4 weeks
* ultraviolet B (UVB) or topical therapy (other than over-the-counter (OTC) moisturizers and shampoos) within the past 2 weeks (including topical corticosteroids, vitamin A and D analogues) with the exception of betamethasone valerate lotion (0.01%) for treatment of scalp lesions, and triamcinolone cream (0.1%) for lesions at least 3 inches away from the target lesions
* Receipt of an investigation agent within the past 4 weeks
* Systemic corticosteroid therapy
* Inability to understand consent or comply with protocol (patients will be asked if they understand or have any questions)
* Pregnancy, lactation, or unwillingness to use adequate birth control during the study
* Impaired hepatic function
* Known HIV/AIDS, hepatitis B/C
* Blood dyscrasia
* Epilepsy
* Tardive dyskinesia
* Excessive alcohol consumption (drinking more than two drinks per day on average for men or more than one drink per day on average for women)
* Use of phenothiazine antipsychotics or anticholinergics
* Current use of selective serotonin reuptake inhibitor (SSRI), tricyclic, or norepinephrine reuptake inhibitor antidepressants or use within 6 weeks of beginning the study
* Concurrent use of anti-seizure drugs, with the exception of gabapentin for treatment of neuropathy
* Known allergy to fluphenazine or other phenothiazines, sesame oil or sesame seeds
* Known allergy to parabens, para-aminobenzoate (PABA) or benzyl alcohol
* Clinically significant and uncontrolled cardiovascular disease
* corrected QT interval (QTc) \> 450 msec, or evidence of a clinically significant dysrhythmia on ECG
* Operator of heavy machinery
* Pheochromocytoma
* Clinically significant mitral valve disease
* History of breast cancer
* History of seizure disorder
* Occupational exposure to organophosphate insecticides
* Parkinson's disease and other related movement disorders
* Screening Lab abnormalities including:

  * Serum Asparate transaminase (AST) or Alanine transaminase (ALT) \> 2.5 upper limits of normal
  * Creatinine ≥ 1.6 mg/dL
  * Bilirubin ≥ 1.5 mg/dL
  * White blood cell (WBC) count \< 3 x 10\^9 /L
  * Platelets \< 100 x 10\^9/L
  * Hemoglobin \< 10 g/dL in females or \< 12g/dL in males
  * Glucose ≥ 200 mg/dL
  * Fasting blood sugar ≥ 126 mg/dL
* Concurrent use of drugs listed in Appendix E of protocol

Primary outcomes:
measure: Change in Target Lesion Scoring Evaluated at Baseline and 4 Weeks
timeFrame: 4 weeks
Secondary outcomes:
measure: Change in the Target Lesion Visual Analog Scale (VAS) Score for Pruritus Evaluated at Baseline and 4 Weeks
timeFrame: 4 weeks
measure: Safety Outcome Measures
timeFrame: 8 weeks
measure: Fluphenazine Serum Levels Measured at Baseline, 2 Hours Post Dose and 1 Week Post Dose.
timeFrame: 1 week
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center, Department of Dermatology
state: Massachusetts
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School, Psoriasis Center of Excellence
state: New Jersey
Study officials:
affiliation: Tufts Medical Center, Department of Dermatology
name: Alice B. Gottlieb, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gupta MA, Guptat AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol Venereol. 2001 Nov;15(6):512-8. doi: 10.1046/j.1468-3083.2001.00278.x.