Efficacy Signals in a 12-week Trial of Clavulanic Acid to Decrease Cocaine Use

Background There is urgent need for effective medication to treat cocaine use disorder (CUD). Clavulanic acid (CLAV) is a clinical stage medication that has potential for treating CUD. Methods Sixty-four participants with CUD were randomized and received either 500 mg/day CLAV or matched placebo in a 12-week outpatient study, with dose escalation to 750 mg/day in week 5 with continued use. Results There was no statistically significant improvement in the CLAV treatment group compared to the placebo group. However, women taking CLAV reduced use. Starting at week 4, women reported significantly more days without cocaine use relative to baseline than women taking placebo. During the last 3 weeks of the study, women taking CLAV had a median of 4.0 more days without cocaine per week relative to baseline compared to 0.6 days in the placebo group. CLAV treatment also reduced cocaine withdrawal symptoms in women relative to baseline compared to the placebo over the first 3 weeks of the study. No such trends were identifiable in men. Conclusion At the 500-750 mg/day dose there is a signal that CLAV is associated with a reduction in the number of days of cocaine use in women with CUD. Men with CUD did not benefit from CLAV treatment at these doses. CLAV for 12 weeks was safe and reasonably well tolerated in people with CUD. Future studies should refine a therapeutic dose for men with CUD and further elucidate the effect of CLAV on the observed effects in women.