Enhanced vasoconstrictor potency of the fixed combination calcipotriol plus betamethasone dipropionate in an innovative aerosol foam formulation vs. other corticosteroid psoriasis treatments

Abstract

Background: An aerosol foam formulation of fixed combination calcipotriol 50 μg/g (Cal) and betamethasone 0.5 mg/g (as dipropionate; BD) has been developed for psoriasis vulgaris treatment.

Objective: To compare Cal/BD aerosol foam pharmacodynamic activity with Cal/BD ointment and with other topical corticosteroids of different potencies by assessing vasoconstrictor potential.

Methods: A Phase I, single-centre, investigator-blinded, vehicle-controlled, intra-individual comparison vasoconstriction study. Healthy volunteers received a single application on selected sites of: Cal/BD aerosol foam, clobetasol propionate 0.5 mg/g cream (CP; very potent), Cal/BD ointment (potent), fluocinolone acetonide 0.25 mg/g ointment (FA; moderately potent), BD aerosol foam and aerosol foam vehicle. A seventh untreated site acted as a negative control. Skin blanching was assessed by visual (primary response criterion) and colorimetric a* and L* measurements (secondary criteria), and was analysed over time (6-32 h post-application).

Results: Thirty-five healthy volunteers were included. All active treatments led to significantly greater skin blanching than control. By visual assessment, skin blanching with Cal/BD aerosol foam was significantly less compared with CP cream [mean AUC0-32 2560 vs. 3831; mean difference = -1272; 95% confidence interval (CI): -1598, -945; P < 0.001], similar to BD aerosol foam (mean AUC0-32 2560 vs. 2595; mean difference = -35; 95% CI: -362, 292; P = 0.83) and significantly greater than Cal/BD ointment (mean AUC0-32 2560 vs. 2008; mean difference = 552; 95% CI: 225, 878; P = 0.001) and FA ointment (mean AUC0-32 2560 vs. 1981; mean difference = 578; 95% CI: 251, 905; P < 0.001). Colorimetric assessments a* and L* also indicated significantly reduced skin blanching with Cal/BD aerosol foam compared with CP cream. No adverse events (AEs) were reported.

Conclusion: Cal/BD aerosol foam can be considered a more potent formulation than Cal/BD ointment and the moderately potent FA ointment, but less potent than the very potent corticosteroid, CP cream.

© 2016 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

Figures

Figure 1

Visual assessment of skin blanching. (a) Box plots of the visual assessment of skin blanching area under the curve (AUC0–32). The horizontal line represents the median and the diamond represents the mean, with the box representing the IQR, the whiskers representing the range within 1.5 × IQR and the circle showing the outliers (observations falling outside of 1.5 × IQR). (b) Mean visual assessment of skin blanching score obtained at each time point from two independent, trained observers. †Higher score indicates greater degree of skin blanching. BD, betamethasone 0.5 mg/g (as dipropionate); Cal, calcipotriol 50 μg/g; CP, clobetasol propionate 0.5 mg/g cream; FA, fluocinolone acetonide 0.25 mg/g ointment; IQR, interquartile range.

Figure 2

Colorimetric assessment of skin blanching. (a) Box plots of baseline‐adjusted, untreated control site‐corrected values of skin colour change measured by the colorimetric parameter a* (Δa*) area under the curve (AUC0–32). The horizontal line represents the median and the diamond represents the mean, with the box representing the IQR and the whiskers showing the range within 1.5 × IQR. (b) Mean Δa* skin blanching score obtained from two successive measurements at each time point. †Lower score indicates greater degree of skin blanching. BD, betamethasone 0.5 mg/g (as dipropionate); Cal, calcipotriol 50 μg/g; CP, clobetasol propionate 0.5 mg/g cream; FA, fluocinolone acetonide 0.25 mg/g ointment; IQR, interquartile range.