Austedo does not improve tics in pediatric patients with Tourette syndrome

Austedo did not efficaciously treat tics linked to Tourette syndrome in children and adolescents, according to results of a randomized clinical trial published in JAMA Network Open.

The study revealed no new safety signals for Austedo (deutetrabenazine; Teva Pharmaceuticals), a vesicular monoamine transporter 2 inhibitor approved by the FDA to treat chorea associated with Huntington disease and tardive dyskinesia in adults.

“In a pilot study in adolescents with [Tourette syndrome (TS)], deutetrabenazine was generally well tolerated and significantly reduced tic severity,” Joseph Jankovic, MD, of Baylor College of Medicine in Texas, and colleagues wrote. “Based on these results, clinical development of deutetrabenazine was continued in the Alternatives for Reducing Tics in TS (ARTISTS) program.

“Here we report results from the ARTISTS 1 study, which evaluated the efficacy, safety and tolerability of flexible, response-driven doses of deutetrabenazine in children and adolescents with TS,” they added.

Researchers analyzed data of children and adolescents aged 6 to 16 years with TS and active tics that prompted distress or impairment according to the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS). They randomly assigned 59 participants to deutetrabenazine (mean age, 11.5 years; 90% boys) and 60 participants to placebo (mean age, 11.5 years; 85% boys), titrated during 7 weeks to an optimal level. They followed this with a 5-week maintenance period. A total of 48 mg per day represented the maximum daily deutetrabenazine dose.

Change from baseline to week 12 in YGTSS-TTS served as the primary efficacy end point. Changes in Tourette Syndrome–Clinical Global Impression, Tourette Syndrome–Patient Global Impression of Impact and Child and Adolescent Gilles de la Tourette Syndrome–Quality of Life Activities of Daily Living subscale score served as key secondary end points.

Jankovic and colleagues evaluated safety according to treatment-emergent adverse events, vital signs, questionnaires and laboratory parameters.

Results showed no significant difference in YGTSS-TTS score at week 12 between the two groups, with a least squares mean difference of –0.7 (95% CI, –4.1 to 2.8). Researchers reported that the groups had no nominally significant differences for key secondary end points. A total of 38 (66%) patients who received deutetrabenazine and 33 (56%) who received placebo had treatment-emergent adverse events that were generally mild or moderate.

“The reason for the diminished improvement with deutetrabenazine from week 9 to 12 while the placebo effect increased is unknown,” Jankovic and colleagues wrote. “This is consistent with findings from the phase 3 ARTISTS 2 study, which found that fixed doses of deutetrabenazine demonstrated favorable numeric differences but did not significantly reduce tics in TS compared with placebo at the end of the trial.

“Future examination of pharmacokinetic data collected during these studies may provide insights into whether responses to deutetrabenazine differ based on drug and active drug metabolite exposure,” they added.