rambazole dose and side effects being studied

Written by on February 20, 2007 in Accutane and Roaccutane with 0 Comments

This AAD Poster Session shows that the study of Rambazole is continuing, this time dosage and side effects are being investigated.

Tolerability, safety, and pharmacokinetics of single and multiple oral
dosages of R115866 in healthy volunteers,
Marina Cools, PhD, Barrier Therapeutics, Geel, Belgium; Geert Cauwenbergh,PhD, Barrier Therapeutics, Geel, Belgium; Fre´de´ric Vanhoutte, MD, JanssenResearch Foundation, Beerse, Belgium; Lieve Vandeplassche, PhD, Barrier Therapeutics, Geel, Belgium

Introduction: R115866 is a novel benzothiazole derivative which potently and selectively inhibits cytochrome P450-dependent all-trans retinoic acid (RA) catabolism. R115866 enhances endogenous RA levels primarily in tissues where RA is metabolized. Currently, an oral clinical development program for psoriasis and acne has been started.

Objectives: Assess safety, tolerability, and pharmacokinetics of single and multiple oral dosages of R115866. Design: In a first trial, male volunteers were dosed with a single dose of 0.6, 1.25, 2.5, 5, 10, or 20 mg R115866 or placebo. In the 2nd trial, male volunteers were treated b.i.d. for 8 days with dosages of 0.5, 2, and 4 mg R115866 or placebo.

Safety and Tolerability: No clinically relevant changes in laboratory and cardiovascular parameters were seen in either trials. No AEs were observed with 0.6 mg, 3 of 6, and 2 of 6 subjects receiving 1.25 and 2.5 mg reported AEs; all subjects receiving 5mg or higher experienced AEs, the most frequent were erythema and skin peeling. After multiple dosing, the AEs reported were those known to be associated with increased levels of RA in tissues. Most frequent AEs were dry mouth and dry skin. Additionally, a dose-dependent incidence of headache was shown. No SAEs or withdrawal due to AEs were reported. Pharmacokinetics and pharmacodynamics (multidosing trial) PK data are summarized below. Steady-state plasma levels of R115866 were reached after one day dosing. All treatments with R115866 resulted in increases in endogenous RA plasma levels; the total placebo-corrected increase at day 1 averaged 1.8, 2.8, and 2.6 ng/mL and 0.7, 1.4, and 1.9 ng/mL at day 8 for the different dosages of R115866.

Discussion: Four mg R115866 b.i.d. was considered medically safe, but moderately tolerated due to cutaneous RA-related effects. Treatment with 0.5 and 2mg R115866 b.i.d. was well tolerated. These doses are recommended to continue clinical development.

Supported by Barrier Therapeutics.

Poster Abstract P2782, American Academy of Dermatology, 65th Annual Meeting February 2-6, 2007, Washington, DC. Published in Journal of the American Academy of Dermatology Volume 56, Number 2.

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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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