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A phase II dose-finding study looking at the safety and therapeutic range of the drug incyclinide (CollaGenex) for the treatment of acne found that the drug had an excellent side-effect profile similar to placebo. The study showed that incyclinide, a chemically modified doxycycline that has strong anti-inflammatory properties, but no antibiotic activity, had the greatest reduction of inflammatory acne lesions at a dosage of 20 mg, and the drug's makers say they expect even better results at higher doses.
A phase 2 dose-finding study measuring safety and therapeutic range of incyclinide showed an excellent side-effect profile similar to placebo, which some say could represent the first major development in acne treatment in years.
Incyclinide (CollaGenex) is a chemically modified doxycycline that has strong anti-inflammatory properties, but has the advantage of presenting no antibiotic activity.
The dose-finding study - double-blind and placebo-controlled - involved 302 acne patients at 27 centers, with patients divided among four arms to receive either a placebo capsule or a 5 mg, 10 mg or 20 mg incyclinide capsule, administered once a day for 12 weeks.
In the four treatment groups, the average number of inflammatory lesions at baseline was about 24. The study found that the minimum effective incyclinide dose was established to be 10 mg.
The greatest reduction of inflammatory lesions was observed in the 20 mg patient group, in which a 25.9 percent reduction in lesions was observed at week three, compared to a 9.4 percent reduction in the in-cohort placebo group.
At weeks six, nine and 12, the reductions in inflammatory lesions for the 20 mg incyclinide group was 36.0 percent, 36.1 percent and 31.7 percent, respectively, compared to 17.5 percent, 23.8 percent and 26.5 percent, respectively, for the in-cohort placebo group.
The study had a secondary endpoint of evaluating change in the Investigator's Global Assessment score, a subjective measurement of disease severity. The researchers found that the 20-mg group again showed the greatest improvement over placebo, with IGA scores at week six (p=0.065) and at week nine (p=0.026).
The drug was shown to be well-tolerated in patients. Most adverse events were mild to moderate, CollaGenex reports.
Acne patients typically improve during the summer months and worsen during the winter months, even when not receiving treatment. So, the researchers conducted placebo analyses to factor in the possible influence of the seasons in the changes in acne.
The study was not powered to show statistical significance, which the Food and Drug Administration uses to determine effectiveness.
In an effort to find a maximum effective dose, CollaGenex says it will initiate an additional cohort of about 100 patients to look at doses greater than 20 mg, subject to FDA approval.
"We worry about inducing antibiotic resistance in bacteria and about overuse, so to have a drug that will work in acne and not be an antibiotic would be a real advance," says Guy Webster, M.D., Ph.D., clinical professor, Thomas Jefferson University, and member of the CollaGenex Scientific Advisory Board.
Phase 3 clinical trials for the drug are expected to begin in the first quarter of 2008.