Investigation of the Efficacy of Zesteem in Accelerating Early Wound Healing

Study Overview
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Brief Summary
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The purpose of this study is to investigate early wound healing of one application of four different doses of intradermal Zesteem (17β-Estradiol) in male subjects and female subjects two years post-menopausal.

Detailed Description
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Each subject received a total of six, 3mm punch biopsy wounds; three wounds to the upper inner aspect of each arm. Each punch biopsy site was randomly allocated to receive one of six treatments: Zesteem (0.02μg, 0.1μg, 0.2μg and 0.4μg/100μl), Placebo (vehicle), and Standard Care (moist wound healing dressings) only. Zesteem and Placebo were administered to marked, anaesthetised sites, by intradermal injection 10 to 30 minutes before wounding. Sites randomised to receive Standard Care only received no additional treatment before wounding. After wounding, all sites received moist wound healing dressings (Standard Care). Three days after wounding, all biopsy sites were anaesthetised and the wounds excised using a 5mm punch biopsy, for histological analysis. The Investigator closed all excision sites using sutures and Steri-strips to achieve a cosmetically acceptable result. Subjects attended a post-trial follow-up visit (13-18 days after dosing) where their sutures were removed and final safety assessments were performed.

Official Title
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A Single Site, Placebo and Standard Care Controlled, Double Blind, Randomised Trial to Investigate the Efficacy of Four Doses of Zesteem in Accelerating Early Wound Healing of Punch Biopsy Skin Wounds.

Conditions
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Cicatrix, Wound-healing

Intervention / Treatment
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* Drug: Zesteem
* Drug: Zesteem
* Drug: Zesteem
* Drug: Zesteem
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects aged 18-85 years, and female subjects who are at least two years postmenopausal (quantified by a serum test result of estradiol <90 pmol/L and FSH > 31 IU/L) who have given written informed consent Subjects with a BMI within the permitted range for their height using Quetelet's index-weight (kg)/height² (m). The permitted index is 15-55 kg/m2 Subjects with, in the opinion of the investigator, clinically acceptable results for laboratory safety tests performed within 28 days of the first trial dose administration Exclusion Criteria: Subjects who on direct questioning and physical examination have history or evidence of hypertrophic or keloid scarring Subjects with tattoos or previous scars within 3cm of the area to be biopsied Afro-Caribbean subjects are excluded because of the increased susceptibility to hypertrophic and keloid scarring Subjects who have had surgery in the area to be biopsied within one year of the first dosing day Subjects with a history of a bleeding disorder Subjects with a skin disorder that is chronic or currently active and which the Investigator considers will adversely affect the healing of the acute wounds or involves the areas to be examined in this trial Subjects with any clinically significant medical condition or history that would impair wound healing including: significant rheumatoid arthritis, chronic renal impairment significant for their age, significant hepatic impairment (LFTs >3 times upper limit of normal), congestive heart failure, current active malignancy or history of malignancy in the last 5 years, immunosuppression or chemotherapy within the last 12 months, a history of radiotherapy or diabetes mellitus Subjects with a history of hypersensitivity to any of the drugs or dressings used in this trial Subjects who are taking, or have taken any investigational product or participated in a clinical trial in the three months prior to first trial dose administration Subjects who are taking regular, continuous, oral corticosteroid therapy Subjects undergoing investigations or changes in management for an existing medical condition Subjects with a history of drug abuse Subjects with a positive drugs of abuse test for cocaine, amphetamines, methamphetamines, opiates or benzodiazepines during the screening period Subjects who, in the opinion of the investigator, are unlikely to complete the trial for whatever reason Female subjects who are currently taking any form of hormone replacement therapy or contraceptive medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intradermal Zesteem<br> | Drug: Zesteem<br>* Intradermal Zesteem, 0.02μg/100μl administered once before punch biopsy<br>* Other names: RN1002;Drug: Zesteem<br>* Intradermal Zesteem, 0.1μg/100μl administered once before punch biopsy<br>* Other names: RN1002;Drug: Zesteem<br>* Intradermal Zesteem, 0.2μg/100μl administered once before punch biopsy<br>* Other names: RN1002;Drug: Zesteem<br>* Intradermal Zesteem, 0.4μg/100μl administered once before punch biopsy<br>* Other names: RN1002;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Intradermal placebo, 100μl administered once before punch biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess acceleration of early wound healing in male and postmenopausal female subjects following administration of intradermal Zesteem. The primary trial endpoint will be the distance travelled by the epithelium over the biopsy site. |  | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and tolerability of intradermal Zesteem in male and post-menopausal female subjects. |  | 13-18 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cicatrix, Scar, Wound-healing, Zesteem, 17β-Estradiol, RN1002