A Phase I, Single-Center, Randomized, Vehicle-Controlled Study, Double-Blind for the Study Preparations and Observer-Blind for the Comparators to Determine the Antipsoriatic Efficacy and Tolerability of Topical Formulations With Ciclosporin in a Psoriasis Plaque Test
A Phase I, Single-Center, Randomized, Vehicle-Controlled Study, Double-Blind for the Study Preparations and Observer-Blind for the Comparators to Determine the Antipsoriatic Efficacy and Tolerability of Topical Formulations With Ciclosporin in a Psoriasis Plaque Test
Ciclosporin is a cyclic nonribosomal polypeptide of 11 amino acids produced by the fungi Tolypocladium inflatum and Cylindrocarpon lucidum. Ciclosporin is a highly efficient immunosuppressant drug widely used in post-allergenic organ transplant to reduce the activity of the subject's immune system and so the risk of organ rejection. Apart from transplant medicine, ciclosporin is also used in the treatment of autoimmune diseases like psoriasis and infrequently in rheumatoid arthritis and related diseases, although it is only used in severe cases.
Ciclosporin blocks the lymphocytes, especially the T-lymphocytes, in the G0- or G1-phase of the cell cycle. Moreover it inhibits the production and release of lymphokines including interleukin 2 or the T-cell growth factor.
Generally ciclosporin is taken orally (capsule or solution)or by injection in doses of 1.5 to 5.5 mg/kg/day. In the topical cutaneous emulsion presented here, ciclosporin is available at a concentration of 0.5 and 1.5%.
The purpose of this study is the demonstration of antipsoriatic efficacy and tolerability of topical cutaneous ciclosporin in subjects with psoriasis vulgaris.
Psoriasis is a common dermatological disorder, consisting of both an inflammatory and a hyperproliferative component. Scaly, erythematous infiltrated skin lesions are indicative of psoriasis vulgaris. The disease is characterized micromorphologically by epidermal hyperplasia with incomplete differentiation, intraepidermal accumulation of polymorphonuclear neutrophils, elongated papillae containing dilated, tortuous capillaries and lymphohistiocytic infiltrate.
Since the underlying cause of the disease remains unknown, causal therapy is not possible. The complex clinical picture necessitates a polypragmatic therapeutic approach. Typical therapies include phototherapy and photochemotherapy, topical treatment with corticosteroids, vitamin D3 analogs, coal-tar preparations and dithranol, and systemic treatment with retinoids, methotrexate and ciclosporin (oral or injection).
In the present study the topical cutaneous ciclosporin formulation for topical treatment of psoriasis will be tested in low-dose for efficacy and tolerability. Two concentrations of the ciclosporin formulation (0.5% and 1.5%), the corresponding vehicle, a marketed corticoid preparation and a marketed topical Vitamin-D-analog will be tested simultaneously in the same patient. Five test fields located at the torso and at the extremities will be examined per subject, and will be treated non-occlusively on 22 study days over a period study of 26 days.
Experimental measurements (sonography) and clinical assessments will be performed at baseline and on some study days.
Inclusion Criteria:
Exclusion Criteria: