Tolerability and Bioavailability of the P144 Peptide Inhibitor of TGF-β1 After Topical Administration in Healthy Volunteers

• Status: Completed
• Trial end date: 2007-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Transforming growth factor-beta 1 (TGF-β1) is consistently over expressed in most fibrotic diseases and displays a variety of profibrotic effects in fibroblasts. Activation of TGF-β receptors induces the activation of several kinase signalling cascades leading to the phosphorylation of SMAD proteins as well as to the activation of SMAD-independent kinases that collectively activate ECM synthesis and fibroblast growth and differentiation into myofibroblasts. TGF-β1 is one of the main mediators in the fibrotic process, associated to both scarring and a long list of pathologies related to chronic inflammation and which affect all type of organs and tissues. An increase in TGF-β1 mRNA and protein levels has been described in these processes. Peptide 144 (P144) is the acetic salt of a 14mer peptide from human TGF-β1 type III receptor (betaglycan). P144 TGF-β1-inhibitor has been specifically designed to block the interaction between TGF-β1 and TGF-β1 type III receptor, thus blocking its biological effects. P144 has shown significant antifibrotic activity in mice receiving repeated subcutaneous injections of bleomycin, a widely accepted animal model of human scleroderma, and could contribute to the development. The purpose of this study is to assess the tolerability and safety of topical application of P144 in healthy volunteers.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: ISDIN
• Collaborator: Digna Biotech S.L.

Criteria

Inclusion Criteria:

• Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed.

• Age between 18 and 45 years old

• Skin phenotype I to IV following Fitzpatrick's classification scale

• BMI between 20-29 kg/sqm

• Not clinically relevant alterations in: arterial pressure, cardiac frequency, analytical values (Hematology, Biochemistry, Urianalysis, Coagulation, Serology, Toxics)

Exclusion Criteria:

• Pregnany or lactancy

• Allergy to any medication

• Subjects with skin illnesses or systemic illnesses with skin afectation

• History of drug abuse or regular consumption of alcohol

• Participation in other clinical trials 3 months before the signature of the informed consent

• UV exposure or sun exposure on the zone to be treated

• History of skin hypersensitivity

• Chronic treatment with anti-inflammatories or anti-histaminics

• Treatment with corticoids on the previous month

• Hyperpigmentation on the zone to be treated