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 AUC_0-32 2560 vs. 3831; mean difference = -1272; 95% confidence interval (CI): -1598, -945; P < 0.001], similar to BD aerosol foam (mean AUC_0-32 2560 vs. 2595; mean difference = -35; 95% CI: -362, 292; P = 0.83) and significantly greater than Cal/BD ointment (mean AUC_0-32 2560 vs. 2008; mean difference = 552; 95% CI: 225, 878; P = 0.001) and FA ointment (mean AUC_0-32 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.

Figure 1

Visual assessment of skin blanching. (a) Box plots of the visual assessment of skin blanching area under the curve (AUC_0–32). 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 (AUC_0–32). 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.