- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00356200
Fluphenazine Decanoate for Psoriasis
Ascending-Dose, Double-Blind, Placebo-Controlled, Bilateral Study of Intralesional Fluphenazine Decanoate in Psoriasis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02111
- Tufts-New England Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adults 18 to 65 years of age with psoriasis, in general good health
- Must have symmetric target lesions approximately 2-4 cm in diameter on each side of the body (e.g., thighs) with baseline target lesion score of 6 or higher (scale of 0-12) for each target
- Women of childbearing potential must agree to use two forms of contraception for the duration of the study
Exclusion Criteria:
- 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 PUVA (psoralen plus ultraviolet A) 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)
- Receipt of an investigational agent within the past 4 weeks
- Systemic corticosteroid therapy
- Inability to understand consent or comply with protocol
- Pregnancy, lactation, or unwillingness to use adequate birth control during the study
- Impaired hepatic function
- Known Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis B/C
- Blood dyscrasia
- Epilepsy
- Tardive dyskinesia
- Excessive alcohol consumption
- Current use of selective serotonin reuptake inhibitors (SSRI), tricyclic, or norephinephrine 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
- Use of phenothiazine antipsychotics or anticholinergics
- Known allergy to fluphenazine decanoate or other phenothiazines
- Known allergy to parabens/para-aminobenzoic acid (PABA), benzyl alcohol, sesame oil or sesame seeds
- Clinically significant mitral valve disease
- Clinically significant and uncontrolled cardiovascular disease
- QTc >450 msec, or evidence of a clinically significant dysrhythmia on electrocardiography (ECG)
- Operator of heavy machinery
- Pheochromocytoma
- History of breast cancer
- History of seizure disorder
- Occupational exposure to organophosphate insecticides
- Parkinson's disease and other related movement disorders
- Lab abnormalities including:
- Alanine aminotranferease (ALT)/aspartate aminotransferase (AST) ≥ 2X upper limit of reference range
- Creatinine ≥ 1.5X upper limit of reference range
- Bilirubin ≥ 2X upper limit of reference range
- Absolute total lymphocyte or polymorphonuclear leucocyte count ≤ 1000/uL or ≥ 3X upper limit of ref range
- Platelets ≤ 80,000/uL
- Hemoglobin ≤ 8.0 g/dL
- Glucose ≥ 200 mg/dL
- Fasting blood sugar ≥ 126 mg/dL
- Concurrent use of drugs listed in Appendix F
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Fluphenazine treated
Treated with fluphenazine
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Target Lesion Score at Week 4 Compared to Baseline
Time Frame: Baseline to week 4
|
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).
|
Baseline to week 4
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline.
Time Frame: Baseline to week 4
|
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).
|
Baseline to week 4
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Tutrone WD, Kagen MH, Barbagallo J, Weinberg JM. Biologic therapy for psoriasis: a brief history, II. Cutis. 2001 Dec;68(6):367-72.
- Kipnis CD, Myers WA, Opeola M, Gottlieb AB. Biologic treatments for psoriasis. J Am Acad Dermatol. 2005 Apr;52(4):671-82. doi: 10.1016/j.jaad.2004.12.032. No abstract available.
- Gupta MA, Gupta AK. Psychiatric and psychological co-morbidity in patients with dermatologic disorders: epidemiology and management. Am J Clin Dermatol. 2003;4(12):833-42. doi: 10.2165/00128071-200304120-00003.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Skin Diseases, Papulosquamous
- Psoriasis
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Dopamine Agents
- Dopamine Antagonists
- Fluphenazine
- Fluphenazine depot
- Fluphenazine enanthate
Other Study ID Numbers
- FP-CL1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Psoriasis
-
ProgenaBiomeRecruitingPsoriasis | Psoriasis Vulgaris | Psoriasis of Scalp | Psoriatic Plaque | Psoriasis Universalis | Psoriasis Face | Psoriasis Nail | Psoriasis Diffusa | Psoriasis Punctata | Psoriasis Palmaris | Psoriasis Circinata | Psoriasis Annularis | Psoriasis Genital | Psoriasis GeographicaUnited States
-
Clin4allRecruitingPsoriasis of Scalp | Psoriasis Nail | Psoriasis Palmaris | Psoriasis Genital | Psoriasis PlantarisFrance
-
Innovaderm Research Inc.CompletedScalp Psoriasis | Pustular Palmo-plantar Psoriasis | Non-pustular Palmo-plantar Psoriasis | Elbow Psoriasis | Lower Leg PsoriasisCanada
-
Centre of Evidence of the French Society of DermatologyRecruitingPsoriasis | Psoriasis Vulgaris | Psoriasis of Scalp | Psoriatic Plaque | Psoriasis Universalis | Psoriasis Palmaris | Psoriatic Erythroderma | Psoriatic Nail | Psoriasis Guttate | Psoriasis Inverse | Psoriasis PustularFrance
-
UCB Biopharma S.P.R.L.CompletedModerate to Severe Psoriasis | Generalized Pustular Psoriasis and Erythrodermic PsoriasisJapan
-
AmgenCompletedPsoriasis-Type Psoriasis | Plaque-Type PsoriasisUnited States
-
Janssen Pharmaceutical K.K.RecruitingGeneralized Pustular Psoriasis | Erythrodermic PsoriasisJapan
-
Eli Lilly and CompanyCompletedGeneralized Pustular Psoriasis | Erythrodermic PsoriasisJapan
-
TakedaRecruitingGeneralized Pustular Psoriasis | Erythrodermic PsoriasisJapan
-
Herlev and Gentofte HospitalRecruitingMyocardial Infarction | Myocardial Ischemia | Heart Diseases | Cardiovascular Diseases | Heart Failure | Stroke | Psoriasis | Heart Failure, Diastolic | Psoriasis Vulgaris | Cardiovascular Risk Factor | Heart Failure, Systolic | Left Ventricular Dysfunction | Psoriasis Universalis | Psoriasis Face | Psoriasis Diffusa | Psoriasis... and other conditionsDenmark
Clinical Trials on Fluphenazine Decanoate
-
National Institute of Mental Health (NIMH)Completed
-
Immune ControlCompletedMultiple Myeloma and Plasma Cell NeoplasmUnited States
-
University of Maryland, BaltimoreCompletedSchizophreniaUnited States
-
Immune ControlUnknownMultiple MyelomaUnited States
-
Tufts Medical CenterImmune ControlCompleted
-
Centre for Addiction and Mental HealthCanadian Institutes of Health Research (CIHR)CompletedPathological GamblingCanada
-
Case Western Reserve UniversityNational Institute of Mental Health (NIMH)CompletedSchizophrenia | Schizo Affective Disorder | Medication NonadherenceTanzania
-
National Institute of Allergy and Infectious Diseases...CompletedHIV Infections | HIV Wasting SyndromeUnited States, Puerto Rico
-
National Institute of Diabetes and Digestive and...CompletedMuscle Weakness | End-Stage Renal Disease
-
Centre Hospitalier St AnneEtablissement Public de Santé Barthélemy Durand; Groupe Hospitalier Paul GuiraudNot yet recruitingSchizophrenia; PsychosisFrance