Randomized Withdrawal Study Design to Evaluate the Persistence of the Therapeutic Effect of Deutetrabenazine in the Treatment of Tardive Dyskinesia
Background: The long-term open-label extension study of rollover subjects (n=343) from the ARM-TD and AIM-TD trials evaluating the safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia (TD) presents an opportunity to objectively assess deutetrabenazine’s therapeutic effect.
Methods: A short randomized withdrawal (RW) period was added to the protocol primarily to evaluate the persistence of therapeutic effect. Patients receiving deutetrabenazine for up to 3 years could participate in a 1-week, blinded, RW period followed by a 12-week follow-up period in which patients resumed treatment with deutetrabenazine. In the withdrawal period, patients were randomized 1:1 to continue their current dose of deutetrabenazine or matching placebo for 1 week. Because the half-life of deutetrabenazine is ~9 hours, complete elimination is estimated to occur after 2 days of drug withdrawal. Therefore, after a 1-week withdrawal from deutetrabenazine, TD symptoms are expected to return in a manner distinguishable from symptoms in patients who are still being treated with deutetrabenazine. The primary efficacy measure is Abnormal Involuntary Movement Scale (AIMS) score (items 1–7), assessed by central raters. An analysis of covariance model will be used to analyze the change in AIMS score from the pre- to post-withdrawal period. Safety will be evaluated at pre- and post-withdrawal visits.
Conclusions: This RW component of the open-label extension study will assess in a well-controlled clinical study the persistence of deutetrabenazine’s therapeutic effect in patients with TD. Results of the RW efficacy analysis, together with long-term safety data, will provide scientific evidence to inform treatment decisions.
This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.
