Phase I Study of Topical CRx-191 in Normal Healthy Volunteers

Sponsor

Zalicus (Industry)

Overall Status

Completed

CT.gov ID

NCT00544687

Collaborator

(none)

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: CRx-191 Drug: mometasone furoate Drug: nortriptyline HCl Drug: Karison® Creme Drug: Vehicle	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase I, Single-Center, Randomized, Vehicle and Active-Controlled Study to Assess and Compare the Atrophy-Causing Potential of Topical CRx-191 Formulations in Healthy Volunteers

Study Start Date :

Sep 1, 2007

Actual Study Completion Date :

Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 CRx-191 (0.1% mometasone furoate + 0.05% nortriptyline HCl)	Drug: CRx-191 topical (mometasone furoate + nortriptyline HCl)
Experimental: 2 CRx-191 (0.1% mometasone furoate + 0.1% nortriptyline HCl)	Drug: CRx-191 topical (mometasone furoate + nortriptyline HCl)
Active Comparator: 3 0.1% mometasone furoate	Drug: mometasone furoate topical mometasone furoate
Active Comparator: 4 0.1% nortriptyline HCl	Drug: nortriptyline HCl topical nortriptyline HCl
Active Comparator: 5 Karison® Creme (clobetasol-17-propinate 0.05%)	Drug: Karison® Creme topical Karison® Creme (clobetasol-17-propinate 0.05%)
Placebo Comparator: 6 Vehicle (placebo)	Drug: Vehicle topical (placebo)

Outcome Measures

Primary Outcome Measures

Full skin thinning produced by treatment of CRx-191 in comparison with its components at corresponding dose levels, and vehicle with a marketed corticosteriod. Assess tolerability and safety of CRx-191. [28 Days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subject must voluntarily give written informed consent
Subject must be at least 18 years of age
Subject must have healthy skin on which reddening can be easily recognized in the area of the test 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; systemic contraceptive (combined oral contraceptive, implant, injection), or safe intrauterine device (IUD)
Written informed consent obtained

Exclusion Criteria:

Acne, suntan, eczema, hyper- or hypopigmentation, or tattoos in the test fields
Dark skinned persons whose skin color prevents ready assessment of skin reactions
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, TSH < LLN, or receiving thyroid medication
Severe liver disease (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) laboratory values that exceed 1.5x ULN)
Inflammatory dermatoses (e.g. atopic dermatitis, psoriasis), bacterial, viral, or fungal skin infections; facial rosacea
Active varicella, tuberculosis, syphilis or post-vaccine reactions
Autoimmune disease (e.g., lupus erythematosis)
Known allergic reactions or hypersensitivity to any of the components of the study preparations
Allergy to adhesives on the patches used for occlusion 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 human immunodeficiency virus (HIV) antibody
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
Subjects who require medications that inhibit the cytochrome P450 (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
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