The study was conducted in the United States. It was randomized, double-blind, and placebo-controlled. 253 adult participants with acute mania were enrolled. All had a baseline YMRS score of at least 25. Bipolar medications were suspended during screening. Lorazepam was allowed as a rescue medication. Eligible participants received either 0.75 mg of RAP-219 once daily or placebo. The treatment period lasted three weeks in an inpatient setting.
Results showed a statistically significant least squares improvement of 3.1 points over placebo on the YMRS scale at week 3 (P=0.045). Patients on RAP-219 saw a mean LS decrease of 15.4 points. All 11 YMRS items improved with RAP-219 versus placebo. Specific improvements in irritability and disruptive behavior reached nominal significance (P < 0.05).
Fewer than 20% of RAP-219 patients reported adverse events leading to study discontinuation. Common side effects of current bipolar medications, such as orthostatic hypotension and akathisia, were not reported. Somnolence was less frequent with RAP-219 (0.8%) than with placebo (3.1%).
Abraham N. Ceesay, CEO of Rapport, emphasized that tolerability is critical for long-term adherence. He noted that adverse effects often cause patients to stop therapy, leading to relapse. RAP-219 offers a new mechanism of action for bipolar mania. Jeffrey Sevigny, MD, Rapport's Chief Medical Officer, stated that the drug demonstrated significant improvement in manic symptoms with a favorable safety profile. These results will guide the Phase 3 trial design. Phase 3 studies are expected to begin in the second half of 2027. RAP-219 is also being evaluated for treatment-resistant focal epilepsy.