Vapitadine (Barrier Therapeutics) is an investigational oral antihistamine that belongs to a new structural class of H1-selective, nonsedating agents. Results of a randomized, placebo-controlled clinical trial in adults with atopic dermatitis demonstrated its efficacy for relieving itch and added to an existing database showing vapitadine has an excellent safety profile.
San Antonio - Treatment with the investigational oral antihistamine vapitadine significantly improves itch symptoms in adult patients with atopic dermatitis, without causing any signs of sedation, according to the results of a multicenter, randomized, double-blind, placebo-controlled trial.
"Vapitadine, which is being developed by Barrier Therapeutics, represents a new structural class of H1-selective, nonsedating antihistamines.
"It has very high affinity for the H1 receptor and has a completely different chemical structural from antihistamines that are currently commercially available," says Braham Shroot, Ph.D., chief scientific officer, Barrier Therapeutics, at the American Academy of Dermatology's 2008 Winter Meeting.
"In addition, there was some indication from investigator assessments that modest effects were noted in the atopic lesions in this exploratory trial, but, those benefits were not statistically significant," Dr. Shroot tells Dermatology Times.
"However, the potential of this agent to favorably resolve atopic dermatitis is of key interest to us. These data are still being mined. In addition, now that a safe and effective dose level for itch relief has been established, we are looking forward to future studies to investigate whether vapitadine improves atopic lesions if given for a longer duration," he says.
The randomized, placebo-controlled study evaluating vapitadine in atopic dermatitis patients was conducted in Europe. It enrolled 43 patients who began double-blind treatment with vapitadine 60 mg or placebo twice daily for seven days following an initial three- to seven-day run-in phase.
All patients also treated their atopic lesions daily with a hydrocortisone acetate 1 percent cream and an emollient.
Patients self-assessed itch severity twice daily using a 100 mm visual analogue scale and recorded the data in a diary. The mean change from baseline was calculated using these data.
In addition, patients were asked to rate itch relief at the end of the treatment period using a nine-point scale in which -4 represents extreme deterioration and +4 reflects almost complete or complete relief.
Significant benefits of vapitadine were noted for both patient-rated endpoints. Vapitadine treatment was associated with a significantly greater mean reduction from baseline itch score compared with placebo, -14.8 vs. -4.9, respectively, and the mean itch relief scores at the end of treatment showed a significantly more pronounced effect in the vapitadine group compared with the placebo-treated controls, 1.6 vs. 0.2, respectively.
"Nine of the 22 patients in the vapitadine-treated group achieved an itch relief score greater than 2, which is indicative of a major treatment effect, compared with none of the 21 placebo-treated patients," Dr. Shroot says.
The study also included extensive safety evaluations, the results of which were all favorable. There were no reports of sedation, somnolence or sleepiness; no clinically important changes in cardiovascular or laboratory safety parameters; and no serious adverse events.
"The safety findings reinforced what was observed in earlier clinical studies - the overall incidence of adverse events in this randomized trial was lower in the vapitadine group than among the placebo-treated controls," Dr. Shroot says.
The antihistamine activity of vapitadine was initially assessed in a canine model, where it was found to be a potent inhibitor of Ascaris-induced skin reactions in dogs and to have greater potency and a longer duration of action compared with cetirizine or loratadine.
An initial clinical study conducted in healthy volunteers, using the classical histamine-induced wheal and flare reaction, showed that oral vapitadine had a rapid onset of action, less than 60 minutes, and a long-lasting antihistamine effect of more than 24 hours.
A subsequent dose-ranging clinical safety trial evaluated the sedative effects of vapitadine and found no sedation occurred with administration of a daily dose of up to 150 mg for eight days.
"These early data encouraged us to look at this compound in various itch-related disease states, and ultimately, we hope to also develop it as a treatment of atopic dermatitis in children," Dr. Shroot says.