Ascending-Dose, Double-Blind, Placebo-Controlled, Study of Intralesional Fluphenazine Hydrochloride for Psoriasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Change in Target Lesion Scoring Evaluated at Baseline and 4 Weeks
研究概览
简要总结
The objective of this study is to assess the safety and biologic activity of intralesional injection of fluphenazine in adult subjects with psoriasis.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.)
排除标准
- •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
- •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
研究组 & 干预措施
Placebo
The sterile placebo: Bacteriostatic Sodium Chloride for Injection.
干预措施: Placebo (Drug)
Fluphenazine
This will be an ascending dose study with the first cohort of 5 subjects dosed at 100 µg/mL, followed by cohorts at 500 and 2500 µg/mL. Dosing will be on Days 0, 7 and 14 and will consist of 5, or 10, 100 µL injections into the psoriatic lesion. The number of injections will depend on the lesion size. As this is a vehicle controlled study, subjects will receive intralesional injections of both drug and placebo, each into a separate target plaque, in a randomized fashion.
干预措施: Fluphenazine (Drug)
结局指标
主要结局
Change in Target Lesion Scoring Evaluated at Baseline and 4 Weeks
时间窗: 4 weeks
Actual change in target lesion score comparing 4 week score with baseline score. Improvement is positive, worsening is negative. Target lesions scores range from 0 (no disease) to 12 (severe disease), and are scored based on the sum of erythema (0-4), induration (0-4) and scale (0-4) scores.
次要结局
- Change in the Target Lesion Visual Analog Scale (VAS) Score for Pruritus Evaluated at Baseline and 4 Weeks(4 weeks)
- Safety Outcome Measures(8 weeks)
- Fluphenazine Serum Levels Measured at Baseline, 2 Hours Post Dose and 1 Week Post Dose.(1 week)