oral rambazole and psoriasis: phase IIA study from AAD Poster

Written by on March 24, 2006 in Accutane and Roaccutane with 0 Comments

Oral R115866 in patients with moderate to severe plaque-type psoriasis: Safety evaluation from a phase IIA trial

Peter van de Kerkhof, MD, PhD, University Hospital Nijmegen, Princeton, NJ,
United States; Joahan Mertens, Barrier Therapeutics, Geel, Belgium; Peter
Steijlen, MD, PhD, University Hospital Maastricht, Maastricht, Netherlands

R115866 is a second-generation retinoic acid metabolism-blocking Agent (RAMBA), which has been shown to generate retinoid–mimetic biologic effects in various retinoid-sensitive animal models of keratinization by increasing endogenous retinoic acid (RA) levels.

Objective: The objective of this trial was to assess the efficacy and safety of a oncedaily oral dose of 1 mg R115866 for 8 weeks in patients with moderate to severe plaque-type psoriasis.

Patients and Methods: Open-label, single-arm, multicenter trial with 17 patients diagnosed with moderate to severe plaque-type psoriasis. Patients were treated orally once daily with 1mg of R115866 for 8 weeks. Safety parameters were assessed through clinical monitoring (hematology, biochemistry, endocrinology, and urinalysis), cardiovascular safety monitoring, assessment of hypervitaminosis A tolerance, and plasma RA measurements at baseline visit, at the end of the 1-, 2-, 4- and 8-week treatment phase and after a 2-week follow-up period.

Results: At the end of the 8-week treatment phase, the median PASI score relative to baseline was 49%. No deaths or serious adverse events (AEs) occurred. Most AEs were mild to moderate (33.7% and 52.3%); the most frequent AEs were skin and appendages disorders (52.8%, n = 16) and gastrointestinal disorders (20.8%, n = 13). Severe AEs observed in more than 1 subject were pruritus (n = 5) and xerosis (n = 2). Laboratory values normal at baseline and out-of-range in at least 2 subjects at 2 visits throughout treatment/follow-up were for hemoglobin, ALAT, ASAT (n = 2), chloride (n = 3), and triglycerides (n = 6). Hypervitaminosis A–related symptoms were mild to moderate, xerosis and pruritus being the most frequent. The greatest shift from baseline was observed for cheilitis. Predose plasma levels of endogenous RA remained constant during the treatment phase. Postdose plasma concentrations of endogenous RA were increased versus predose at all time points.

Conclusion: This phase IIa trial indicates that oral treatment with R115866 reduces PASI scores in the tested population, supporting further evaluation through a full development program. The safety of 1 mg of R115866, given once daily for 8 weeks, is supported by the finding that plasma levels of endogenous RA rapidly return to baseline after treatment, thereby limiting the accumulation of RA in body tissues and the AEs associated with systemic retinoid treatment.

Author disclosure: Nothing disclosed at press time. 100% sponsored by Barrier Therapeutics.

Poster Discussion Session P2828, American Academy of Dermatology, 64th Annual Meeting, March 3-7 2006, San Francisco.

Supplement to Journal of The American Academy of Dermatology, March 2006, Volume 54, Number 3.

Read more about: Accutane and Roaccutane

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About the Author: David Pascoe started the Rosacea Support Group in October 1998. .

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