The positive results came from a 3 fixed-dose Phase III trial involving nearly 300 patients.
Deutetrabenazine (Austedo), which the US Food and Drug Administration (FDA) approved for the treatment of Huntington’s disease chorea on April 3, 2017, reduced the motor symptoms of tardive dyskinesia (TD) in the recently published ARM-TD study — a randomized, controlled, multicenter clinical trial.
Now, the study has shown the efficacy and safety of 2 fixed doses of deutetrabenazine for TD.
TD is a movement disorder caused by extended exposure to dopamine-receptor—blocking drugs such as antipsychotic agents. As such, clinicians often manage TD by decreasing the dose of the causative agent or discontinuing it entirely.
However, many patients still need drug therapy for schizophrenia, schizoaffective disorder, or treatment-resistant mood disorder. As a result, specialists need options for managing TD while patients continue antipsychotic drug treatment.
To determine whether fixed doses of deutetrabenazine could be used to tailor TD therapy based on dyskinesia control and tolerability in each patient, an international team of researchers performed a Phase III, placebo-controlled trial of 3 fixed doses of the drug in nearly 300 patients at 75 centers in the US and Europe.
Karen Anderson, MD, (pictured) a psychiatrist specializing in neuropsychiatry and an associate professor of psychiatry and neurology in the Department of Psychiatry Research Division at Georgetown University Medical Center in Washington, DC, led the research team. Anderson is also director of the Huntington's Disease Care, Education and Research Center at MedStar Georgetown University Hospital in Washington, DC.
AIM-TD enrolled 298 patients, aged 18 to 80 years, who had tardive dyskinesia for at least 3 months before screening. Between October 29, 2014, and August 19, 2016, the team used interactive response technology to assign patients randomly in a 1:1:1:1 ratio to receive 1 of 3 fixed daily dosages of deutetrabenazine or a matching placebo.
The investigators stratified the random assignment based on patients’ use of dopamine-receptor antagonists. All investigators, patients, site personnel, and the study sponsor, Teva Pharmaceuticals, were masked to patients’ group assignment while patients were receiving treatment or placebo.
The doses of active drug investigated were 12 mg, 24 mg, and 36 mg. All patients assigned to active treatment started with a daily dosage of 12 mg, which was increased through week 4 until they reached the dose they were randomized to receive. Once the randomized dose was reached, it was maintained for an additional 8 weeks.
The AIM-TD study’s primary efficacy endpoint was change in the Abnormal Involuntary Movement Scale (AIMS) score from baseline to study end at week 12 in patients with at least 1 rating on this scale after the baseline rating. The investigators did the safety analysis in all 293 patients who received any study drug and did the primary efficacy analysis in the modified intention-to-treat population of 222, which consisted of all patients with a baseline AIMS score of at least 6 and at least 1 rating on this scale after the baseline rating.
At the study’s end, the team found that least-squares mean AIMS score improved from its baseline level by the following number of points by treatment group:
Differences in least-squares mean AIMS score between treatment groups after 12 weeks were as follows:
In contrast, the team found that the rate of adverse events (AEs) was similar between treatment groups. The rate of AEs by treatment group was as follows:
In the safety population, 2 patients (1%) died. One died in the 24-mg/day group, and another died in the 36-mg/day group. However, the investigator and sponsor deemed neither death attributable to the study drug.
From their findings, the investigators concluded that both the 24-mg and the 36-mg doses of deutetrabenazine provided statistically significant reduction in symptoms of tardive dyskinesia “with favourable safety and tolerability.”
“These findings suggest that dosing regimens could be individualized and tailored for patients on the basis of dyskinesia control and tolerability,” the researchers wrote.
A report on the study, “Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial,” was published online in Lancet Psychiatry.