Systemic and Local Diffusion of Ethanol After Administration of Ethanol 96% Formulated in a Gel and Ethanol 98% Solution by the Percutaneous Route, in Patients With Congenital Venous Malformations:Pharmacokinetic, Pharmacodynamic and Clinical Study.

NCT00462462 | Completed Phase 2 Results

• 1 other identifier: L00122 GI 201 (ORF)
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 2

Brief Summary

Absolute ethanol has been used "off-label" as an unmodified formulation (solution) in Congenital Venous Malformations (CVM). Despite its effectiveness, absolute ethanol appears difficult to handle because of its high diffusion capacity outside the CVM and in the blood circulation. A less diffusible ethanol-based product (ethanol gel) has been developed in order to minimize systemic and local diffusion capacities of ethanol. Therefore, the pharmacokinetic parameters and their clinical and paraclinical outcomes between ethanol gel 96% and absolute ethanol need to be carried out. FDA Office of Orphan Products Development (FDA OOPD) : Funding source.

Conditions

Congenital Venous Malformation

Outcome Measures

Primary Outcomes (1)

• Systemic Exposure to Ethanol With the Two Test Products: Determination of the Maximum Plasma Concentration (Cmax)

  Blood samples were performed, just before infusion, then 5 min, 10 min, 20 min, 40 min, 60 min, 90 min, and 120 min after infusion at the first site, then every 60 min onwards until ethanol levels are found under the detection limit. Cmax was estimated directly from experimental data. If all the ethanol concentrations of a patient was below the limit of quantification of the laboratory (LOQ), Cmax was reported as LOQ/2 for this patient.

  Baseline visit (just before and during test product infusion procedure)

Secondary Outcomes (3)

• Systemic (Cardiopulmonary, Hematological, Metabolic) and Local Outcome of the Two Test Products.

  Study end

• Change in Volume of Congenital Venous Malformation (CVM) From Screening to Study End (Day 112 Visit).

  Screening and study end (Day 112)

• Patient Benefit

  study end

Study Arms (2)

1

EXPERIMENTAL

Ethanol gel

Drug: Ethanol 96% Gel

2

ACTIVE COMPARATOR

Ethanol solution

Drug: Ethanol 98% Solution

Interventions

Ethanol 96% Gel DRUG

1

Ethanol 98% Solution DRUG

2

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of both sexes, of at least 12 years of age,
• For women of childbearing potential, negative pregnancy test at baseline,
• Patients with one clinically and radiologically (MRI) documented lesion diagnosed as CVM (pure or predominant),
• Patients for which an embolosclerotherapy by the percutaneous route is indicated as first line therapy of the test lesion, or for which previous treatments (i.e. surgery, embolosclerotherapy, laser) have been unsuccessful or insufficient,
• Patients with CVM lesional size of at least 12 cm3 (maximum craniocaudal dimension X mean dimension of 3 transverse equispaced measurements X mean dimension of 3 deepness equispaced measurements dimension) at MRI,
• Patients with focal or multifocal CVM lesion, i.e. with one or several well-interconnecting venous spaces and well-defined margins,
• Patients or parents able to follow study instructions and attend study visits,
• Written informed consent from the patients or parents.

You may not qualify if:

• Patients under 12 years of age,
• Pregnant women, nursing mothers and women of childbearing potential with no reliable contraception from more than 2 months,
• Women of childbearing potential with a positive pregnancy test at baseline,
• Patients with CVM of non venous predominance,
• Patients with CVM that are not reachable by the percutaneous route,
• Patients with extensive superficial skin CVM (i.e. with high risk of skin necrosis),
• Patients with a test lesion adjacent to major nerves (e.g. facial nerve in the parotid region, intramuscular regions adjacent to major nerves),
• Patients with facial CVM or bone involvement,
• Patients with small CVM lesion (\<12 cm3 at MRI),
• Patients requiring more than 1 ml/Kg body weight (b.w.) in USA or more than 0.5 ml/Kg b.w. in France, or more than 30 mL of absolute ethanol to infuse,
• Patients with a known allergy to one of the components of the test products,
• Patients with a suspected allergy to iodinate.ed products,
• Patients with abnormal clotting parameters (platelets, partial thromboplastin, prothrombin time),
• Patients with an active inflammatory episode of the test lesion (i.e. acute or subacute swelling of the test lesion),
• Patients with complex malformations (e.g. Klippel-Trenaunay syndrome, Blue Rubber Bled Nevus syndrome, Muco-cutaneous familial venous malformations, Mafucci's syndrome),

Sponsors & Collaborators

• Orfagen: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (2)

Johns Hopkins Medical Institutions

Baltimore, Maryland, 21287, United States

Location

Hôpital Bretonneau Service de neuroradiologie

Tours, 37044, France

Location

MeSH Terms

Interventions

Ethanol; Gels; Solutions

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Orfagen

info@orfagen.com

+33 5 34 50 64 62

Study Officials

• PATRICK DUPUY, MD

  ORFAGEN LABORATORIES (France)

  STUDY DIRECTOR

• SALLY E MITCHELL, MD

  Johns Hopkins Medical Institution (Baltimore, USA)

  PRINCIPAL INVESTIGATOR

• Denis HERBRETEAU, MD

  Hôpital Bretonneau (Tours, France)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2007
• First Posted: April 19, 2007
• Study Start: May 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: January 15, 2015
• Results First Posted: December 12, 2014

Record last verified: 2015-01

Locations

FR (1); US (1)