title: Use of Longitudinal Dose-Response Modeling to Support the Efficacy and Tolerability of Alitretinoin in Severe Refractory Chronic Hand Eczema (CHE).
abstract: Longitudinal dose-response analyses of alitretinoin (an investigational agent in the US) were conducted to supplement results from phase III studies in severe, refractory chronic hand eczema, with objectives to address several outstanding development issues (e.g., optimal dose, possible factors affecting efficacy and/or tolerability). Models were fitted to the physicians' global assessment score and triglycerides over time. Five hundred trials were simulated to evaluate the relevance of findings. Analyses clarified that the optimal dose of alitretinoin was 30 mg once daily, where response rates were ∼10% over placebo at 12 weeks and increased by 5-7% over placebo for every 4 weeks thereafter, for up to 24 weeks. Elderly subjects had higher magnitudes of efficacy and an increased probability of high triglycerides. Results from analyses sufficiently addressed the development issues, thereby adding to the weight of evidence supporting the efficacy and safety of alitretinoin in the treatment of severe, refractory chronic hand eczema.
authors.affiliation: Quantitative Sciences, GlaxoSmithKline (GSK), Research Triangle Park North Carolina and Upper Merion, Pennsylvania, USA ; Currently at Nuventra Pharma Sciences, Research Triangle Park North Carolina and Upper Merion, Pennsylvania, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Schmith
authors.affiliation: Quantitative Sciences, GlaxoSmithKline (GSK), Research Triangle Park North Carolina and Upper Merion, Pennsylvania, USA.
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.affiliation: Pharmacometrica Longcol, France.
authors.forename: R
authors.initials: R
authors.lastname: Gomeni
authors.affiliation: Clinical Development, Stiefel, a GSK Company, Research Triangle Park North Carolina, USA.
authors.forename: O
authors.initials: O
authors.lastname: Graff
authors.affiliation: Quantitative Sciences, GlaxoSmithKline (GSK), Research Triangle Park North Carolina and Upper Merion, Pennsylvania, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Hamedani
authors.affiliation: Regulatory Affairs, GSK, Research Triangle Park North Carolina, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Troughton
authors.affiliation: Medicines Development Leader, Stiefel, a GSK Company, Research Triangle Park North Carolina, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Learned