Taclonex (Calcipotriene / Betamethasone Dipropionate Topical) - Clinical Pharmacology

CLINICAL PHARMACOLOGY

Taclonex^® Ointment:

Taclonex^® Ointment combines the pharmacological effects of calcipotriene hydrate and betamethasone dipropionate as described below. 

In a vasoconstrictor study, the skin blanching response of Taclonex^® Ointment was consistent with that of a potent corticosteroid.

Calcipotriene

Pharmacokinetics: Calcipotriene metabolism following systemic uptake is rapid and occurs in the liver. The primary metabolites of calcipotriene are less potent than the parent compound.

Betamethasone dipropionate

Like other topical corticosteroids, betamethasone dipropionate has anti-inflammatory, antipruritic and vasoconstrictive properties. However, while the physiologic, pharmacologic, and clinical effects of the corticosteroids are well known, the exact mechanisms of their actions in psoriasis vulgaris are uncertain.  

Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

Taclonex^® Ointment was applied once daily for 4 weeks to adult patients (N = 12) with psoriasis vulgaris to study its effects on the hypothalamic-pituitary-adrenal (HPA) axis. Of eleven patients tested, none demonstrated adrenal suppression as indicated by a 30-minute post-stimulation cortisol level ≤ 18 mcg/dL.

However in another clinical study of Taclonex^® Ointment, one subject (N = 19) demonstrated adrenal suppression.

CLINICAL STUDIES

In an international, multi-center, double-blind, vehicle- and active-controlled, parallel-group study, 1,603 patients with mild to very severe psoriasis vulgaris on trunk and limbs were treated once daily for 4 weeks. Patients were randomized to one of four treatment arms: Taclonex^® Ointment, calcipotriene hydrate 50 mcg/g in the same vehicle, betamethasone dipropionate 0.64 mg/g in the same vehicle, and vehicle alone. The mean age of the patients was 48.4 years and 60.5% were male. Most patients had disease of moderate severity at baseline. 

Efficacy was assessed as the proportion of patients with absent or very mild disease according to the Investigator’s Global Assessment of Disease Severity at end of treatment (4 weeks). “Absent” disease was defined as no evidence of redness, thickness, or scaling. “Very mild disease” was defined as controlled disease, but not entirely cleared: lesions with some discoloration with absolutely minimal thickness, i.e. the edges to the lesion(s) could just be felt.

PERCENTAGE OF PATIENTS WITH ABSENT OR VERY MILD DISEASE ACCORDING TO THE INVESTIGATOR’S GLOBAL ASSESSMENT OF DISEASE SEVERITY AT END OF TREATMENT (4 WEEKS)*.

	Taclonex® Ointment N = 490	Calcipotriene N = 480	Betamethasone dipropionate N = 476	Vehicle N = 157
Absent or very mild disease	48.0%	16.5%	26.3%	7.6%

* PATIENTS WITH MILD DISEASE AT BASELINE WERE REQUIRED TO HAVE “ABSENT” DISEASE TO BE CONSIDERED A SUCCESS.

In addition to the pivotal study (N = 490), four randomized, double-blind, vehicle- or active-controlled, parallel-group studies were conducted and provided supportive evidence of efficacy. These studies included a total of 1,058 patients treated with Taclonex^® Ointment once daily for up to 4 weeks.