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

Zalicus

Status and phase: Completed; Phase 1

Conditions: Atopic Dermatitis

Treatments: Drug: Active ingredient free vehicle cream of CRx-197; Drug: nortriptyline HCl + loratadine; Drug: mometasone furoate; Drug: nortriptyline HCl

Study type: Interventional

Funder types: Industry

Identifiers

NCT00721331

CRx-197-001

EudraCT # 2008-000611-15

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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20 participants in 5 patient groups, including a placebo group

CRx-197 high dose (0.1% nortriptyline HCl + 0.3% loratadine)

Experimental group

Treatment:

Drug: nortriptyline HCl + loratadine

Drug: nortriptyline HCl + loratadine

CRx-197 low dose (0.1% nortriptyline HCl + 0.1% loratadine)

Experimental group

Treatment:

Drug: nortriptyline HCl + loratadine

Drug: nortriptyline HCl + loratadine

0.1% nortriptyline HCl

Experimental group

Treatment:

Drug: nortriptyline HCl

0.1% mometasone furoate

Active Comparator group

Treatment:

Drug: mometasone furoate

Active ingredient free vehicle cream of CRx-197

Placebo Comparator group

Treatment:

Drug: Active ingredient free vehicle cream of CRx-197