Treprostinil Iontophoresis : a Pharmacodynamic and Pharmacokinetic Study

Study Overview
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Brief Summary
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The purpose of the study is to assess skin blood flow after non-invasive local administration of treprostinil by using a low-intensity current (i.e. iontophoresis) on the forearm and the fingers of healthy volunteers and patients with systemic sclerosis. The investigators also aim at assessing the systemic bioavailability and dermal diffusion of treprostinil iontophoresis.

Detailed Description
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Digital ulcerations are a complication of systemic sclerosis (SSc). Available treatments (i.e. IV iloprost) induce major adverse effects, limiting the use of such therapies. Iontophoresis is a non invasive route of administration of drugs. In experimental and clinical preliminary studies, the investigators have shown that iontophoresis of treprostinil on the forearm of healthy subjects induces a sustained increase in skin blood flux and that it is well tolerated (clinicaltrials.gov NCT01082484, manuscript in press). The investigators therefore aim at validating this proof of concept on the digits of SSc patients.

Official Title
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Pharmacodynamic and Pharmacokinetic Assessment of Treprostinil Iontophoresis on the Forearm and the Fingers

Conditions
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Scleroderma, Systemic

Intervention / Treatment
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* Drug: Cutaneous iontophoresis of treprostinil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cutaneous systemic scleroderma with sclerosed fingers Exclusion Criteria: pregnant or breast-feeding women any chronic disease (in the control group) smoking

Ages Eligible for Study
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Minimum Age: 18 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: Cutaneous iontophoresis of Treprostenil<br> | Drug: Cutaneous iontophoresis of treprostinil<br>* Cutaneous iontophoresis of treprostinil 0.1mg/ml, on the forearm and the fingers. (charge 40-240 mC).<br>|
| Placebo Comparator: Cutaneous iontophoresis of placebo<br> | Drug: Cutaneous iontophoresis of treprostinil<br>* Cutaneous iontophoresis of treprostinil 0.1mg/ml, on the forearm and the fingers. (charge 40-240 mC).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) of cutaneous blood flow | Cutaneous blood flow assessed with Laser Speckle Contrast Imaging (LSCI) | 0, 15min, 30 min, 1h, 2h, 4h, 6h, 8h, 10h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treprostinil blood concentration | AUC of treprostinil concentration from the end of iontophoresis until 10 hours after iontophoresis | 0, 15min, 30 min, 1h, 2h, 4h, 6h, 8h, 10h | 
| Treprostinil dermal concentration | AUC of treprostinil concentration in the dermis (collected with microdialysis) from the end of iontophoresis until 10 hours after iontophoresis | 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treprostinil, Scleroderma, Iontophoresis