Safety and Tolerability Study of ZEP-3 Cream (0.1% and 1.0%), Administered Topically In Healthy Volunteers

Study Overview
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Brief Summary
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It is a phase I randomized, double blind, placebo-controlled, dose-escalating study to assess safety, tolerability and pharmacokinetics (PK) data of 0.1% and 1.0% ZEP-3 cream, administered topically up to 5 consecutive treatment days in healthy volunteers. This is a single center trial. It is anticipated that the study will be conducted at the Department of Dermatology, at the Sheba Medical Center, Ramat Gan, Israel. The screening/enrollment visit includes a PK study for 24h following a single IP topical application. After a 24h washout time break, the subject will enter the treatment period for 5 consecutive treatment days followed by a follow up visit 1 and 5 days after end of treatment.

Detailed Description
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The primary endpoints of this study are: Safety evaluation - To demonstrate ZEP-3 cream safety in terms of skin irritation score. Safety evaluation - To demonstrate ZEP-3 cream safety in terms of type and severity of reported adverse events. Tolerability evaluation - To demonstrate ZEP-3 cream tolerability in terms of treatment compliance by the treated volunteers. The secondary endpoints of this study are: Systemic absorption PK profile. Dermal absorption PK profile (Optional). Subject safety will be assessed following treatment by ZEP-3 cream, using measurements of the following variables: Dermal reaction parameters Physical examination Vital Signs (HR, BP, RR, Body temperature) 12 lead ECG data Laboratory tests (CBC, blood chemistry, coagulation functions, urinalysis) Adverse events recording Change in concomitant medications

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose-escalating Study to Assess Safety, Tolerability and Pharmacokinetics of 0.1% and 1.0% ZEP-3 Cream, Administered Topically in Healthy Volunteers.

Conditions
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Healthy

Intervention / Treatment
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* Drug: 0.1% ZEP-3 cream
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must voluntarily sign and date the written Informed Consent prior to any study specific procedures Subject, either men or women is between 18 and 50 years of age. Subject, Body mass index (BMI) is within the normal to overweight range (See appendix 2) Subject must have healthy skin on which reddening can be easily recognized in the area where they will place the test article Subject must be free from a condition/disease that the investigator feels interferes with the interpretation of the study results. Subject is willing to participate in the study and adhere to the study protocol Females of childbearing potential should either be surgically sterile, or should use a highly effective medically accepted contraceptive regimen. Exclusion Criteria: Subject has 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 Subject with history of skin disorders or any active skin condition involving the test fields including but not limited to bacterial, viral, or fungal skin infections, acne, rosacea UV therapy or significant UV exposure in the four weeks before treatment application Subject with renal failure (Cr > 2 mg/dl) or Subject with impaired hepatic function (ALT, AST 2-fold higher than normal upper limit value). Cardiac disease, including recent myocardial infarction, any degree of heart block or other cardiac arrhythmias and valvular heart disease Subject suffers from an autoimmune disease (Diabetes, Lupus. Chron ect.) History of malignancy Sever illness or surgery within the previous 3 months (except for minor cosmetic or dental procedures) Treatment with any investigational agent in another clinical trial within 1 month prior to start of this study. Female subject who is pregnant , lactating, or with a positive pregnancy test History of drug or alcohol abuse (as defined by the Investigator)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 0.1% ZEP-3 cream<br>250 mg of ZEP-3 Cream 0.1% is applied on the right ventral forearm and 250 mg placebo is applied on the left ventral forearm 4 times daily | Drug: 0.1% ZEP-3 cream<br>* Topical application of 250mg ZEP-3 cream (0.1%) vs. placebo 4 times daily The IP is applied to in advanced demarcated sites in a dose escalating mode to 3 different treatment area sizes: small area of 2x1 cm (2 cm2), medium area of 2x5 cm (10 cm2), and large area of 4x5 cm (20 cm2). The IP ZEP-3 cream will be applied on both ventral forearms (one application site per forearm) in a non-occlusive mode, spread and rubbed over the demarcated area. Right arm, single treatment area - ZEP-3 (0.1%) Left arm, single treatment area - Placebo cream<br>* Other names: novel synthetic peptide;|
| Other: placebo<br>250 mg of ZEP-3 Cream 1.0% is applied on the right ventral forearm and 250 mg placebo is applied on the left ventral forearm 4 times daily | Drug: placebo<br>* Topical application of 250mg ZEP-3 cream (1.0%) vs. placebo 4 times daily The IP is applied to in advanced demarcated sites in a dose escalating mode to 3 different treatment area sizes: small area of 2x1 cm (2 cm2), medium area of 2x5 cm (10 cm2), and large area of 4x5 cm (20 cm2). The IP ZEP-3 cream will be applied on both ventral forearms (one application site per forearm) in a non-occlusive mode, spread and rubbed over the demarcated area. Right arm, single treatment area - ZEP-3 (1.0%) Left arm, single treatment area - Placebo cream<br>* Other names: novel synthetic peptide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Topical skin safety evaluation | Skin irritation | Change in skin clinical presentation up to 5 consecutive treatment days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic absorption | PK profile | During 24 hours following initial application | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, Pharmacokinetic profile, ZEP-3 Cream (0.1% and 1.0%), administered topically