Study of CRx-191 to Assess Activity in Plaque Psoriasis

Sponsor

Zalicus (Industry)

Overall Status

Completed

CT.gov ID

NCT00557739

Collaborator

Bioskin GmbH (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

CRx-191 is a proprietary synergistic combination drug candidate being evaluated by CombinatoRx for topical psoriasis therapy. CRx-191 was identified via a proprietary screening assay for novel drug combinations demonstrating enhanced inhibition of tumor necrosis factor- alpha and interferon-gamma release, cytokines that are implicated in the pathogenesis of psoriasis.

This clinical trial will assess the effectiveness of CRx-191 in reducing the psoriatic infiltrate band thickness as measured by transdermal ultrasound. All subjects will receive all treatments in separate test fields, with intra-individual comparison of the treatments.

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis	Drug: mometasone furoate Drug: nortriptyline HCl Drug: Vehicle (placebo)	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Single-Center, Randomized, Double-Blind, Vehicle-Controlled Study to Assess the Activity of CRx-191 in Reducing the Psoriatic Infiltrate Band Thickness in Plaque Psoriasis

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Jan 1, 2008

Actual Study Completion Date :

Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 CRx-191 (0.1% mometasone furoate + 0.05% nortriptyline HCl)	Drug: mometasone furoate Topical 0.1% mometasone furoate Drug: nortriptyline HCl Topical 0.05% or 0.1% nortriptyline HCl
Experimental: 2 CRx-191 (0.1% mometasone furoate + 0.1% nortriptyline HCl)	Drug: mometasone furoate Topical 0.1% mometasone furoate Drug: nortriptyline HCl Topical 0.05% or 0.1% nortriptyline HCl
Active Comparator: 3 0.1% mometasone furoate	Drug: mometasone furoate Topical 0.1% mometasone furoate
Active Comparator: 4 0.05% nortriptyline HCl	Drug: nortriptyline HCl Topical 0.05% or 0.1% nortriptyline HCl
Active Comparator: 5 0.1% nortriptyline HCl	Drug: nortriptyline HCl Topical 0.05% or 0.1% nortriptyline HCl
Placebo Comparator: 6 Vehicle (placebo)	Drug: Vehicle (placebo) Topical placebo

Outcome Measures

Primary Outcome Measures

The primary efficacy endpoint is the difference in reduction from baseline in psoriatic infiltrate at Day 12 between CRx-191 and vehicle. [Day 12]

Secondary Outcome Measures

Differences in reduction from baseline in psoriatic infiltrate at Day 12 between CRx-191 and its components, mometasone furoate and nortriptyline HCI. Demonstrate tolerability and safety of CRx-191. [Day 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject must voluntarily give written informed consent
Subject must be between 18 and 70 years of age
Subject must have chronic plaque psoriasis and stable plaques in an area sufficient for six treatment fields
The physical examination must be without disease findings unless the investigator considers an abnormality to be irrelevant to the outcome of the study
Sexually active females of childbearing potential should either be surgically sterile (hysterectomy or tubal ligation), or should use a highly effective medically accepted contraceptive regimen

Exclusion Criteria:

Erythrodermic, guttate or pustular psoriasis
Cardiac disease, including recent myocardial infarction, any degree of heart block or other cardiac arrhythmias and valvular heart disease
Mania
Narrow angle glaucoma
Hyperthyroidism by medical history, thyroid stimulating hormone (TSH) less than lower limit of normal (LLN), or receiving thyroid medication
Intolerance to Lidocaine
Severe liver disease (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) laboratory values that exceed 1.5x upper limit of normal (ULN))
Inflammatory dermatoses except psoriasis; bacterial, viral and fungal skin infections; facial rosacea
Active varicella, tuberculosis, syphilis or post-vaccine reaction
Autoimmune disease other than plaque psoriasis (e.g. lupus erythematosis and psoriatic arthritis)
Known allergic reactions or hypersensitivity to any of the components of the study preparations
Allergy to adhesives on the hydrocolloid dressing used in this study
UV therapy in the four weeks before the study
History of malignancy (except for treated or excised basal cell carcinoma)
Surgery within the previous 3 months (except for minor cosmetic or dental procedures)
History of drug or alcohol abuse (as defined by the Investigator)
Symptoms of a clinically significant illness in the four weeks before the study that may influence the outcome of the study
Positive for HIV antibody
Subjects who require systemically acting medications for the treatment of psoriasis which might counter or influence the study objectives such as: Methotrexate; Cyclosporine; Anti-TNFα therapies
Subjects who require medications that inhibit the CYP450 2D6 pathway such as: Quinidine; Cimetidine; Type 1 antiarrhythmics; Phenothiazines; Selective serotonin reuptake inhibitors such as fluoxetine, paroxetine, and sertraline; Reserpine, other anticholinergic drugs, and sympathomimetic drugs
Topical treatments for psoriasis (except for salicylic acid in vaseline) in the four weeks preceding and during the study (topical corticosteroids disallowed for eight weeks prior to the study)
Systemic treatments in the two weeks preceding and during the study that may interact with any of the study drugs, such as: Glucocorticoids (po, im, iv); MAO inhibitors; Anti-depressants; Anti-seizure medications; Anti-psychotics; Antihistamines
Treatments in the two weeks preceding and during the study that may aggravate psoriasis, such as: Anti-malarials; Beta-blockers
Participation in another clinical trial and/or treatment received with any investigational agent within one month before the initial dose of study medication
Female subject who is pregnant or lactating
Significant UV exposure in the four weeks before the study
Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's return for follow-up visits on schedule
Other unspecified reasons that, in the opinion of the Investigator or sponsor make the subject unsuitable for enrollment
Subject is institutionalized because of legal or regulatory order