Asclera

CLINICAL PHARMACOLOGY

Mechanism of Action

The active ingredient of Asclera is polidocanol.

Polidocanol is a sclerosing agent that locally damages the endothelium of blood vessels. When injected intravenously, polidocanol induces endothelial damage. Platelets then aggregate at the site of damage and attach to the venous wall. Eventually, a dense network of platelets, cellular debris, and fibrin occludes the vessel. Finally, the occluded vein is replaced with connective fibrous tissue.

Pharmacodynamics

Polidocanol has a concentration- and volume-dependent damaging effect on the endothelium of blood vessels.

Pharmacokinetics

During the major effectiveness study (EASI-trial), scheduled blood samples were taken from a sub-group of 22 patients to measure plasma levels of polidocanol after Asclera (polidocanol injection) treatment of spider and reticular veins. Low systemic blood levels of polidocanol were seen in some patients.

The mean t½ of polidocanol in 4 patients with evaluable data receiving 4.5 -18.0 mg was 1.5 h.

Clinical Studies

Asclera (polidocanol injection) was evaluated in a multicenter, randomized, double-blind, placebo- and comparator-controlled trial (EASI-study) in patients with spider or reticular varicose veins. A total of 338 patients were treated with Asclera (polidocanol injection) [0.5% for spider veins (N=94), 1% for reticular veins (N=86)], sodium tetradecyl sulfate (STS) 1% (N=105), or placebo (0.9% isotonic saline solution) (N=53) for either spider or reticular veins. Patients were predominately female, ranging in age from 19 to 70 years. All of them received an intravenous injection in the first treatment session; repeat injections were given three and six weeks later if the previous injection was evaluated as unsuccessful (defined as 1, 2 or 3 on a 5-point scale, see below). Patients returned at 12 and 26 weeks after the last injection for final assessments.

The primary effectiveness endpoint was improvement of veins judged by a blinded panel. Digital images of the selected treatment area were taken prior to injection, compared with those taken at 12 weeks post-treatment, and rated on a 5-point scale (1 = worse than before, 2 = same as before, 3 = moderate improvement, 4 = good improvement, 5 = complete treatment success); results are shown in Table 2.

Table 2 : Improvement of veins in digital photographs after 12 weeks and 26 weeks

Treatment Group Polidocanol (N=155) STS (N=105) Placebo (N=53)
Digital Photograph Scores at 12 weeks
Mean ± SD (N) 4.5* 4. 2.2  
Digital Photograph Scores at 26 weeks
Mean ± SD (N) 4.5* 4. 2.2  
*p < 0.0001 compared to placebo (Wilcoxon-Mann-Whitney test)

The secondary efficacy criterion was the rate of treatment success, pre-defined as a score of 4 or 5 with patients scoring 1, 2, or 3 considered treatment failures; results are shown in Table 3.

Table 3 : Treatment success rates at 12 weeks and 26 weeks

Treatment success?* Polidocanol (N=155) STS (N=105) Placebo (N=53)
At 12 weeks (Visit 4)
Yes 95%** 92%** 8%
No 5% 8% 92%
Missing 0.6% 0% 0%
At 26 weeks (Visit 5)
Yes 95%** 91%** 6%
No 5% 9% 94%
*Treatment success: Yes= Grade 4 to 5, No= Grade 1 to 3; derived from median of evaluation; **p < 0.0001 compared to placebo.

At 12 and 26 weeks, patients' judgment of the results was assessed by showing them the digital images of their treatment area taken at baseline and asking them to rate their satisfaction with their treatment using a verbal rating scale (1 = very unsatisfied; 2 = somewhat unsatisfied; 3 = slightly satisfied; 4 = satisfied and 5 = very satisfied); results are shown in Table 4.

Table 4 : Patient satisfaction after 12 weeks and 26 weeks

  Polidocanol (N=155) STS (N=105) Placebo (N=53)
Patient satisfaction with treatment after 12weeks (Visit 4)
Satisfied or very satisfied 87%* 64% 14%
Patient satisfaction with treatment after 26weeks (Visit 5)
Satisfied or very satisfied 84%* 63% 16%
*p < 0.0001 compared to STS and placebo

Last reviewed on RxList: 4/16/2010
This monograph has been modified to include the generic and brand name in many instances.

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