r-115866 and Psoriasis
r-115866 has been researched along with Psoriasis* in 3 studies
Reviews
1 review(s) available for r-115866 and Psoriasis
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Talarozole, a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne.
Talarozole, being developed by Barrier Therapeutics Inc under license from Johnson & Johnson, is a potent and selective inhibitor of cytochrome P450 26-mediated breakdown of endogenous all-trans retinoic acid for the treatment of psoriasis and acne. Phase II clinical trials of an oral formulation of talarozole in patients with psoriasis and with acne, and a phase I clinical trial of a topical formulation have been completed. At the time of publication, Barrier Therapeutics had suspended the development of talarozole as part of a series of cost-cutting initiatives; the company had also been acquired by Stiefel Laboratories Inc. No formal announcement had been made regarding the further development of talarozole. Topics: Acne Vulgaris; Animals; Benzothiazoles; Clinical Trials as Topic; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Humans; Psoriasis; Structure-Activity Relationship; Tretinoin; Triazoles | 2008 |
Trials
2 trial(s) available for r-115866 and Psoriasis
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Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study.
The novel systemic all-trans retinoic acid metabolism blocking agent (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all-trans retinoic acid (RA). Well-known effects of RA are normalization of aberrant epithelial growth and differentiation. Hence, rambazole might be beneficial in the treatment of plaque psoriasis.. The dynamics of epidermal proliferation, keratinization, lesional T-cell subsets and cells expressing natural killer (NK)-receptors in plaque psoriasis were assessed during treatment with rambazole, as part of a phase IIa open-label clinical trial.. Six patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0, 2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13, K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained and quantified with image analysis.. At week 2 the mean SUM-score was virtually equal to baseline, which was accompanied immunohistochemically by equal epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in contrast, plaque severity was reduced by 34% from baseline (P < 0.05). Improvements were also detected for epidermal proliferation (-63%; P < 0.01) and K10 expression (+29%; P < 0.01), compared with baseline. No induction of retinoid-specific keratinization (K13, K19) was observed. A nonsignificant reduction of all pathogenic T-cell subsets and cells expressing NK-receptors was observed at week 8 of treatment (P > 0.05).. Clinical efficacy of rambazole is primarily the result of restoring proliferation (Ki67) and differentiation (K10) of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells expressing NK-receptors showed nonsignificant reductions after 8 weeks of treatment with rambazole. Topics: Administration, Oral; Adult; Benzothiazoles; Cell Proliferation; Dermatologic Agents; Female; Humans; Immunohistochemistry; Keratolytic Agents; Male; Middle Aged; Psoriasis; Tretinoin; Triazoles | 2007 |
Oral R115866 in the treatment of moderate to severe plaque-type psoriasis.
R115866 (Rambazole) is a new generation all-trans retinoic acid metabolism blocking agent, highly specific against the retinoic acid 4-hydroxylase. The drug alleviates hyperproliferation and normalizes differentiation of the epidermis in animal models of psoriasis.. To explore the efficacy, safety and tolerability of systemic R115866 in patients with moderate to severe plaque-type psoriasis.. In this open label, single-arm trial, patients were treated with R115866, 1 mg/day for 8 weeks, followed by a 2-week treatment-free follow-up period. Patients were monitored for efficacy and safety.. Nineteen patients (intent-to-treat population) were treated and 14 completed the entire study. Two patients discontinued due to lack of efficacy and three due to adverse events. At the end of the treatment, 26% of the patients showed at least 50% reduction in Psoriasis Area Severity Index (PASI) compared to baseline. Further improvement was observed at the end of the 2-week follow-up period where 47% of the patients showed a 50% or greater reduction in PASI. Kinetic data showed no evidence of accumulation of either R115866 or retinoic acid in plasma. The most common adverse events were pruritus, xerosis, cheilitis and an increase in blood triglycerides. The majority of adverse events were mild to moderate. No deaths or serious adverse events were reported.. Eight-week daily treatment with 1 mg R115866 resulted in a significant reduction in PASI from baseline to end of therapy. Additional improvement was seen after the 2-week follow-up period. The drug was well tolerated. R115866 merits further evaluation to optimize its clinical efficacy and safety profile in moderate to severe plaque-type psoriasis. Topics: Administration, Oral; Adult; Aged; Benzothiazoles; Dermatologic Agents; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psoriasis; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome; Triazoles | 2007 |