Treprostinil Iontophoresis : a Pharmacodynamic and Pharmacokinetic Study

Scleroderma, Systemic Clinical Trial

— TIPPS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01554540
• Other study ID #: DCIC TIPPS 11 18
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: February 7, 2012
• Last updated: July 17, 2013
• Start date: February 2012
• Est. completion date: February 2014

Study information

• Verified date: July 2013
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: February 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cutaneous systemic scleroderma with sclerosed fingers

Exclusion Criteria:

• pregnant or breast-feeding women

• any chronic disease (in the control group)

• smoking

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic

Intervention

Drug:
• Cutaneous iontophoresis of treprostinil
Cutaneous iontophoresis of treprostinil 0.1mg/ml, on the forearm and the fingers. (charge 40-240 mC).

Locations

Country	Name	City	State
France	CIC pharmacology - University Hopsital of Grenoble	Grenoble

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (5)

Blaise S, Roustit M, Millet C, Ribuot C, Boutonnat J, Cracowski JL. Cathodal iontophoresis of treprostinil and iloprost induces a sustained increase in cutaneous flux in rats. Br J Pharmacol. 2011 Feb;162(3):557-65. doi: 10.1111/j.1476-5381.2010.01045.x. — View Citation

Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR. Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci. 2006 Sep;27(9):503-8. Epub 2006 Jul 31. Review. — View Citation

Herrick AL. Vascular function in systemic sclerosis. Curr Opin Rheumatol. 2000 Nov;12(6):527-33. Review. — View Citation

Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Adv Drug Deliv Rev. 2004 Mar 27;56(5):619-58. Review. — View Citation

Murray AK, Moore TL, King TA, Herrick AL. Vasodilator iontophoresis a possible new therapy for digital ischaemia in systemic sclerosis? Rheumatology (Oxford). 2008 Jan;47(1):76-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No