A Phase I Study to Assess the Safety and Tolerability of Topical CRx-197 Formulations in Healthy Volunteers

Sponsor

Zalicus (Industry)

Overall Status

Completed

CT.gov ID

NCT00721331

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This will be a phase I, single center, randomized, vehicle-controlled, blinded study comparing two dosage strengths of CRx-197 cream, nortriptyline, an active comparator (0.1% mometasone) and placebo (the active ingredient free vehicle cream of CRx-197)in healthy volunteers.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: nortriptyline HCl + loratadine Drug: nortriptyline HCl + loratadine Drug: nortriptyline HCl Drug: mometasone furoate Drug: Active ingredient free vehicle cream of CRx-197	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase I, Single-Center, Randomized, Vehicle-Controlled Study to Assess the Safety and Tolerability of Topical CRx-197 Formulations in Healthy Volunteers

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Sep 1, 2008

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CRx-197 high dose (0.1% nortriptyline HCl + 0.3% loratadine)	Drug: nortriptyline HCl + loratadine Topical
Experimental: CRx-197 low dose (0.1% nortriptyline HCl + 0.1% loratadine)	Drug: nortriptyline HCl + loratadine Topical
Experimental: 0.1% nortriptyline HCl	Drug: nortriptyline HCl Topical
Active Comparator: 0.1% mometasone furoate	Drug: mometasone furoate Topical
Placebo Comparator: Active ingredient free vehicle cream of CRx-197	Drug: Active ingredient free vehicle cream of CRx-197 Topical

Outcome Measures

Primary Outcome Measures

Safety and tolerability of CRx-197 as assessed by treatment emergent adverse events, physical exams, vital signs, concomitant medications/procedures and subject assessment of pruritus. [2 months]

Secondary Outcome Measures

Difference in change from baseline in psoriatic infiltrate measured by ultrasound between CRx-197, nortriptyline, active comparator as well as vehicle of CRx-197 and untreated test field(s) [Days 8, 15, 22, 29 and 43]
Difference in change from baseline in erythema measured by chronometry between CRx-197, nortriptyline, active comparator, vehicle of CRx-197, untreated test field(s) and normal skin [Days 8, 15, 22, 29 and 43]
Modified PASI between CRx-197, nortriptyline, active comparator, vehicle of CRx-197, untreated test field(s) [Baseline, and Days 8, 15, 22, 29 and 43]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subject must voluntarily sign and date the written Informed Consent prior to any study specific procedures
Subject must be 18 to 60 years of age
Subject must have healthy skin on which reddening can be easily recognized in the area where they will place the test fields
Subject must be free from a condition/disease that the investigator feels interferes with the interpretation of the study results.
Females of childbearing potential should either be surgically sterile (hysterectomy or tubal ligation), or should use a highly effective medically accepted contraceptive regimen. A highly effective method of birth control is defined as those which result in a lower failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner.

Exclusion Criteria:

Suntan, hyper- or hypo-pigmentation, or tattoos in the area where they will place 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 less than LLN, or subject receiving any thyroid medication
Severe liver disease - ALT laboratory value that exceeds 1.5x ULN
Inflammatory dermatoses (e.g., atopic dermatoses/eczema, psoriasis)
Any skin condition involving the test fields including but not limited to bacterial, viral, or fungal skin infections, acne, 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 treatments
Allergy to adhesives on the patches used for occlusion in the study
UV therapy or significant UV exposure in the four weeks before treatment application
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 treatment application that may influence the outcome of the study
Positive for HIV antibody
Systemic treatments in the four weeks prior to treatment application that may interact with any of the study drugs, such as: Glucocorticoids, MAO inhibitors, anti-depressants, anti-seizure medications, anti-psychotics and anti-histamines
Subjects who require medications that inhibit the CYP450 2D6 pathway such as:Quinidine, Cimetidine, Type 1 anti-arrhythmic, Phenothiazines, Selective serotonin reuptake inhibitors, Reserpine, other anticholinergic drugs, and sympathomimetic drugs
Treatment with any investigational agent within one month before treatment application for this trial
Female subject who is pregnant , lactating, or with a positive pregnancy test
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, make the subject unsuitable for enrollment
Subject is institutionalized because of legal or regulatory order