SAN FRANCISCO – A trial of the anticonvulsant vigabatrin to treat cocaine dependence may have failed because the patients weren't taking it, not because the drug didn't work, the study results have shown.
The National Institute on Drug Abuse will repeat the trial, but this time the investigators will try to enroll people who appear motivated to stop cocaine use so that adherence to treatment can be better measured, Dr. Eugene C. Somoza said at the meeting.
“The trial failed, but we don't think that the drug failed,” said Dr. Somoza of the University of Cincinnati. Vigabatrin is currently indicated for adjunctive treatment of complex partial seizures and infantile spasms. The original double-blind, placebo-controlled trial randomized 186 adults with cocaine dependence to 12 weeks of treatment with placebo or 3 g daily of vigabatrin in two divided doses. The investigators assessed cocaine use during the study through patient self-report and measurements of benzoylecgonine, a long-acting metabolite of cocaine in the urine. Cocaine use did not differ significantly between the groups, suggesting that vigabatrin failed to decrease use of the drug.
Dr. Somoza said he was “very surprised that it didn't work,” because vigabatrin had decreased cocaine use in a similar study of 103 patients in Mexico. In that study, however, investigators observed patients ingesting the drug on 29% of the treatment days. The American study relied on pill counts and patient self-reports to measure treatment adherence, which was rated as 85%.
A subsequent analysis of urine samples retained from the study showed that fewer than 40% of 53 patients in the vigabatrin arm who completed the 12-week study had urine drug levels that would indicate adherence to the medication regimen. The subsequent urinalyses suggested that at 5 of the 11 study sites, fewer than half of the patients had taken the medication as prescribed.
After lack of adherence to the treatment regimen was controlled for, the findings indicated that patients who took vigabatrin used less cocaine than did those who were on placebo, Dr. Somoza said.
The Mexican study enrolled participants who were seeking treatment for their cocaine dependence and who may have been more motivated to adhere to treatment than were participants in the American study, he added.
The study was funded by Catalyst Pharmaceutical Partners, which makes the vigabatrin formulation used in the study. Two of Dr. Somoza's research associates in the study work for the company.