Fluphenazine Decanoate for Psoriasis

• Sponsor: Tufts Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00356200
• Collaborator: Immune Control (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 26.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Fluphenazine Decanoate; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Ascending-Dose, Double-Blind, Placebo-Controlled, Bilateral Study of Intralesional Fluphenazine Decanoate in Psoriasis
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Change in Target Lesion Score at Week 4 Compared to Baseline [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).

Secondary Outcome Measures

1. Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline. [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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts-New England Medical Center	Boston	Massachusetts	United States	02111

Sponsors and Collaborators

• Tufts Medical Center
• Immune Control

Investigators

• Principal Investigator: Alice B Gottlieb, MD, PhD, Tufts Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Review.
• Gupta MA, Guptat AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol Venereol. 2001 Nov;15(6):512-8. Review.
• Kipnis CD, Myers WA, Opeola M, Gottlieb AB. Biologic treatments for psoriasis. J Am Acad Dermatol. 2005 Apr;52(4):671-82.
• Tutrone WD, Kagen MH, Barbagallo J, Weinberg JM. Biologic therapy for psoriasis: a brief history, II. Cutis. 2001 Dec;68(6):367-72. Review.

• ClinicalTrials.gov Identifier: NCT00356200
• Other Study ID Numbers: FP-CL1
• First Posted: Jul 25, 2006
• Last Update Posted: Dec 22, 2010
• Last Verified: Dec 1, 2010

• Additional relevant MeSH terms: Psoriasis; Fluphenazine; Fluphenazine depot; Fluphenazine enanthate

Study Results

Participant Flow

Arm/Group Title	Cohort 1: 10 ug/ml Fluphenazine Decanoate	Cohort 2: 100 ug/ml Fluphenazine Decanoate
Arm/Group Description	Receiving fluphenazine decanoate (10 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body.	Receiving fluphenazine decanoate (100 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body.
Period Title: Cohort 1: 10 ug/ml
STARTED	5	0
COMPLETED	4	0
NOT COMPLETED	1	0
Period Title: Cohort 1: 10 ug/ml
STARTED	0	5
COMPLETED	0	3
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Cohort 1: 10 ug/ml Fluphenazine Decanoate	Cohort 2: 100 ug/ml Fluphenazine Decanoate	Total
Arm/Group Description	Receiving fluphenazine decanoate (10 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body	Receiving fluphenazine decanoate (100 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	5 100%	10 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.6 (11.70)	38.8 (6.69)	39.1 (8.99)
Sex: Female, Male (Count of Participants)
Female	1 20%	2 40%	3 30%
Male	4 80%	3 60%	7 70%
Region of Enrollment (participants) [Number]
United States	5 100%	5 100%	10 100%

Outcome Measures

1. Secondary Outcome

Title	Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline.
Description	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).
Time Frame	Baseline to week 4

Outcome Measure Data

Analysis Population Description

all 5 patients per cohort completed the visit at week 4

Arm/Group Title	Cohort 1, 10 ug/ml Fluphenazine Treated Lesion	Cohort 1, Placebo Treated Lesion	Cohort 2, 100 ug/ml Fluphenazine Treated Lesion	Cohort 2, Placebo Treated Lesion
Arm/Group Description	lesion receiving 10 ug/ml Fluphenazine decanoate (Cohort 1)	lesion treated with placebo (Cohort 1)	lesion receiving 100 ug/ml Fluphenazine decanoate (Cohort 2)	lesion treated with placebo (Cohort 2)
Measure Participants	5	5	5	5
Mean (Standard Deviation) [mm]	-30 (35.07)	-27.2 (34.69)	-18 (34.87)	-32.6 (31.81)

2. Primary Outcome

Title	Change in Target Lesion Score at Week 4 Compared to Baseline
Description	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).
Time Frame	Baseline to week 4

Outcome Measure Data

Analysis Population Description

all 5 patients per cohort completed the visit at week 4

Arm/Group Title	Cohort 1, 10 ug/ml Fluphenazine Treated Lesion	Cohort 1, Placebo Treated Lesion	Cohort 2, 100 ug/ml Fluphenazine Treated Lesion	Cohort 2, Placebo Treated Lesion
Arm/Group Description	Cohort 1 10 ug/ml Fluphenazine decanoate treated lesion	Cohort 1 lesion treated with placebo	Cohort 2 100 ug/ml Fluphenazine decanoate treated lesion	Cohort 2 lesion treated with placebo
Measure Participants	5	5	5	5
Mean (Standard Deviation) [units on a scale]	-1 (2.45)	-0.8 (2.68)	-0.4 (2.19)	-1.5 (2.40)

Adverse Events

Arm/Group Title	Cohort 1: 10 ug/ml Fluphenazine Decanoate		Cohort 2: 100 ug/ml Fluphenazine Decanoate
Arm/Group Description	Receiving fluphenazine decanoate (10 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body		Receiving fluphenazine decanoate (100 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body
All Cause Mortality
	Cohort 1: 10 ug/ml Fluphenazine Decanoate		Cohort 2: 100 ug/ml Fluphenazine Decanoate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1: 10 ug/ml Fluphenazine Decanoate		Cohort 2: 100 ug/ml Fluphenazine Decanoate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: 10 ug/ml Fluphenazine Decanoate		Cohort 2: 100 ug/ml Fluphenazine Decanoate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		4/5 (80%)
Eye disorders
contact lens irritation	0/5 (0%)	0	1/5 (20%)	1
Infections and infestations
cold/sinus symptoms	2/5 (40%)	2	1/5 (20%)	1
cough	0/5 (0%)	0	1/5 (20%)	1
upper respiratory tract infection	0/5 (0%)	0	1/5 (20%)	1
Injury, poisoning and procedural complications
injection site pain	1/5 (20%)	1	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	1/5 (20%)	1	0/5 (0%)	0
Nervous system disorders
dizziness	1/5 (20%)	1	0/5 (0%)	0
Headache	1/5 (20%)	1	0/5 (0%)	0
migraine	0/5 (0%)	0	1/5 (20%)	1
tired	0/5 (0%)	0	1/5 (20%)	1
Renal and urinary disorders
Hematuria	0/5 (0%)	0	1/5 (20%)	1
Skin and subcutaneous tissue disorders
contact dermatitis	0/5 (0%)	0	1/5 (20%)	1
itchy lesions	2/5 (40%)	2	1/5 (20%)	1
lesion pain	1/5 (20%)	1	0/5 (0%)	0
pruritis	0/5 (0%)	0	1/5 (20%)	1
psoriatic lesion spreading	1/5 (20%)	1	0/5 (0%)	0
sunburn (1st degree)	0/5 (0%)	0	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.