Taclonex Scalp

Taclonex Scalp

CLINICAL PHARMACOLOGY

Mechanism of Action

Taclonex® Topical Suspension combines the pharmacological effects of calcipotriene hydrate as a synthetic vitamin D3 analog and betamethasone dipropionate as a synthetic corticosteroid. However, while their pharmacologic and clinical effects are known, the exact mechanisms of their actions in psoriasis vulgaris are unknown.

Pharmacodynamics

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression:

HPA axis suppression was evaluated in two trials (Trial A and B) following the application of Taclonex® Topical Suspension. In Trial A, HPA axis suppression was evaluated in adult subjects (N=32) with extensive psoriasis involving at least 30% of the scalp and, in total, 15-30% of the body surface area. Treatment consisted of once daily application of Taclonex® Topical Suspension on the scalp in combination with Taclonex® Ointment on the body for 4 to 8 weeks. Adrenal suppression as indicated by a 30-minute post-stimulation cortisol level ≤ 18 mcg/dL was observed in 5 of 32 subjects (15.6%) after 4 weeks of treatment and in 2 of 11 subjects (18.2%) who continued treatment for 8 weeks.

In Trial B, HPA axis suppression was evaluated in adult subjects (N=43) with extensive psoriasis involving 15-30% of the body surface area (including the scalp). Treatment consisted of once daily application of Taclonex® Topical Suspension to the body (including the scalp in 36 out of 43 subjects) for 4 to 8 weeks. Adrenal suppression as indicated by a 30-minute post-stimulation cortisol level ≤ 18 mcg/dL was observed in 3 out of 43 subjects (7%) after 4 weeks of treatment and in none of the 36 subjects who continued treatment for 8 weeks.

Effects on Calcium Metabolism

In Trial A described above, the effects of once daily application of Taclonex® Topical Suspension on the scalp in combination with Taclonex® Ointment on the body for 4 to 8 weeks on calcium metabolism were also examined. Following once daily application of Taclonex® Topical Suspension on the scalp in combination with Taclonex® Ointment on the body, elevated urinary calcium levels outside the normal range were observed in two subjects (one at 4 weeks and one at 8 weeks).

In Trial B, the effects on calcium metabolism of once daily application of Taclonex® Topical Suspension to 15-30% of the body surface area (including the scalp) for 4 to 8 weeks were also examined. There was no change in mean serum or urinary calcium levels. Elevated urinary calcium levels outside the normal range were observed in two subjects (one at 4 weeks and one at 8 weeks).

Pharmacokinetics

Absorption

Taclonex® Topical Suspension

The systemic effect of Taclonex® Topical Suspension in psoriasis was investigated in Trials A and B described above. In Trial A, the serum levels of calcipotriene and betamethasone dipropionate and their major metabolites were measured after 4 and 8 weeks of once daily application of Taclonex® Topical Suspension on the scalp in combination with Taclonex® Ointment on the body. Calcipotriene and betamethasone dipropionate were below the lower limit of quantification in all serum samples of the 34 subjects evaluated.

However, one major metabolite of calcipotriene (MC1080) was quantifiable in 10 of 34 (29.4%) subjects at week 4 and in 5 of 12 (41.7%) subjects at week 8. The major metabolite of betamethasone dipropionate, betamethasone 17-propionate (B17P) was also quantifiable in 19 of 34 (55.9%) subjects at week 4 and 7 of 12 (58.3%) subjects at week 8. The serum concentrations for MC1080 ranged from 20-75 pg/mL. The clinical significance of this finding is unknown.

In Trial B, the plasma levels of calcipotriene and betamethasone dipropionate and their major metabolites were measured after 4 weeks of once daily application of Taclonex® Topical Suspension to 15-30% of the body surface area (scalp and non-scalp areas). Calcipotriene and its metabolite MC1080 were below the lower limit of quantification in all plasma samples. Betamethasone dipropionate was quantifiable in 1 sample each taken from 4 of 43 (9.3%) subjects. The metabolite of betamethasone dipropionate (B17P) was quantifiable in 16 of 43 (37.2%) subjects. The plasma concentrations of betamethasone dipropionate ranged from 30.9-63.5 pg/mL and that of its metabolite betamethasone 17-propionate ranged from 30.5-257 pg/mL. The clinical significance of this finding is unknown.

Metabolism

Calcipotriene

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

Calcipotriene is metabolized to MC1046 (the α,β-unsaturated ketone analog of calcipotriene),which is metabolized further to MC1080 (a saturated ketone analog). MC1080 is the major metabolite in plasma. MC1080 is slowly metabolized to calcitroic acid.

Betamethasone dipropionate

Betamethasone dipropionate is metabolized to betamethasone 17-propionate and betamethasone, including the 6β-hydroxy derivatives of those compounds by hydrolysis. Betamethasone 17-propionate (B17P) is the primary metabolite.

Clinical Studies

Clinical Trials on the Scalp

Two multicenter, randomized, double-blind trials were conducted in subjects with scalp psoriasis. In Trial One, 1,407 subjects were randomized to 1 of 4 treatment groups: Taclonex® Topical Suspension, betamethasone dipropionate in the same vehicle, calcipotriene hydrate in the same vehicle, or the vehicle alone. Trial Two did not include a vehicle arm; 1,280 subjects were randomized to 1 of 3 treatment groups: Taclonex® Topical Suspension, betamethasone dipropionate in the same vehicle, or calcipotriene hydrate in the same vehicle. Both trials enrolled subjects with moderate to very severe scalp psoriasis. The majority of subjects had disease of moderate severity at baseline. Subjects were treated once daily for 8 weeks.

Efficacy was assessed as the proportion of subjects at Week 8 with absent or very mild disease according to the Investigator's Global Assessment of Disease Severity. “Clear” was defined as no evidence of redness, thickness or scaling. “Almost clear” was defined as an overall clinical picture of lesions with the presence of minimal erythema. Table 3 contains the response rates in each of these 2 trials.

Table 2: Percentage of Patients with Clear or Almost Clear Disease According to the Investigator's Global Assessment of Disease Severity in Trials on the Scalp

Trial One Taclonex® Topical Suspension
(N = 494)
Betamethasone Dipropionate in vehicle
(N = 531)
Calcipotriene in vehicle
(N = 256)
Vehicle
(N = 126)
Week 2 55.5% 46.1% 18.4% 9.5%
Week 8 70.0% 63.1% 36.7% 19.8%
Trial Two (N = 512) (N = 517) (N = 251) -
Week 2 47.1% 36.4% 12.7% -
Week 8 67.2% 59.6% 41.0% -

Clinical Trial on the Body

One multicenter, randomized, double-blind trial was conducted in subjects with psoriasis vulgaris on non-scalp areas, excluding face, axillae, and groin. In this trial, 1152 subjects were randomized to 1 of 4 treatment groups: Taclonex® Topical Suspension, betamethasone dipropionate in the same vehicle, calcipotriene hydrate in the same vehicle, or the vehicle alone. The trial enrolled subjects with mild to moderate psoriasis vulgaris. Seventy-eight percent of subjects had disease of moderate severity at baseline. Subjects were treated once daily for 8 weeks.

Efficacy was assessed at Week 4 and Week 8 as the proportion of subjects who were “Clear” or “Almost clear” according to the Investigator's Global Assessment of Disease Severity. Subjects with mild disease at baseline were required to be “Clear” to be considered a success. Table 2 contains the response rates in this trial.

Table 3 : Percentage of Patients with Clear or Almost Clear Disease According to the Investigator's Global Assessment of Disease Severity* in Trial on the Body

  Taclonex® Topical Suspension
(N = 482)
Betamethasone Dipropionate in vehicle
(N = 479)
Calcipotriene in vehicle
(N = 96)
Vehicle
(N= 95)
Week 4 13.3% 12.5% 5.2% 2.1%
Week 8 29.0% 21.5% 14.6% 6.3%
* Subjects with mild disease at baseline were required to be “Clear” to be considered a success.

Last reviewed on RxList: 10/29/2012
This monograph has been modified to include the generic and brand name in many instances.

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