Enhanced vasoconstrictor potency of the fixed combination calcipotriol plus betamethasone dipropionate in an innovative aerosol foam formulation vs. other corticosteroid psoriasis treatments.
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 AUC0-322560 vs. 3831; mean difference = -1272; 95% confidence interval (CI): -1598, -945; P < 0.001], similar to BD aerosol foam (mean AUC0-322560 vs. 2595; mean difference = -35; 95% CI: -362, 292; P = 0.83) and significantly greater than Cal/BD ointment (mean AUC0-322560 vs. 2008; mean difference = 552; 95% CI: 225, 878; P = 0.001) and FA ointment (mean AUC0-322560 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.


CONCLUSIONS
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.
Centre de Pharmacologie Clinique Appliquée à la Dermatologie, Nice, France. catherine.queille-roussel@skinpharma.fr.
C
C
Queille-Roussel
LEO Pharma A/S, Ballerup, Denmark.
B
B
Bang
LEO Pharma A/S, Ballerup, Denmark.
F
F
Clonier
Centre de Pharmacologie Clinique Appliquée à la Dermatologie, Nice, France.|Service de Dermatologie, University Hospital of Nice, Nice, France.
J-P
JP
Lacour
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000336:Aerosols; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003124:Colorimetry; D006801:Humans; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000336:Aerosols; D014662:Vasoconstrictor Agents; C055085:calcipotriene; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D002117:Calcitriol