Deutetrabenazine, a vesicular monoamine transporter 2 inhibitor, did not achieve its primary efficacy endpoint of improving total tic score in children and adolescents with Tourette syndrome, according to study results published in JAMA Network Open.
The drug is approved by the US Food and Drug Administration (FDA) to treat chorea associated with Huntington disease and tardive dyskinesia in adults. Preliminary results from previous research suggests deutetrabenazine is safe and effective in reducing tic severity in pediatric patients with troublesome motor and phonic tics associated with Tourette syndrome.
The objective of the current study was to report on the efficacy of deutetrabenazine in reducing motor and phonic tics linked to Tourette syndrome based on results from Alternatives for Reducing Tics in Tourette Syndrome (ARTISTS) 2 study – a multicenter, phase 3, randomized, double-blind, placebo-controlled trial of deutetrabenazine in children and adolescents with Tourette syndrome.
Eligible participants were randomized (1:1:1) to receive high-dose deutetrabenazine (up to 48 mg/d), low-dose deutetrabenazine (up to 36 mg/d), or matching placebo, which was titrated for 4 weeks to the target dose and followed by a 4-week maintenance period. The 8-week treatment period was followed by a 1-week washout period and 1-week follow-up from June 21, 2018, to December 9, 2019.
The change in Yale Global Tic Severity Scale–Total Tic Score (YGTSS-TTS) from baseline to week 8 for high-dose deutetrabenazine compared with placebo was the primary efficacy endpoint.
A total of 158 participants were randomized—52 to the high-dose deutetrabenazine group, 54 to the low-dose deutetrabenazine group, and 52 to the placebo group. Participants had a mean (SD) age of 11.7 (2.6) years, 119 (75%) were boys, and 135 (85%) were White. They had a mean (SD) time of 3.3 (2.8) years since their Tourette syndrome diagnosis, and their mean (SD) baseline YGTSS-TTS was 33.8 (6.6) points.
The change in least-squares (LS) mean (SE) from baseline to week 8 in YGTSS-TTS was –7.8 (1.24) points in the high-dose deutetrabenazine group vs –7.0 (1.16) points in the placebo group (LS mean difference, –0.8 points; 95% CI, –3.9 to 2.3 points; P =.60; Cohen d, –0.11).
Favorable numeric differences were found for changes in secondary endpoints YGTSS-TTS, Tourette Syndrome Clinical Global Impression score, Tourette Syndrome Patient Global Impression of Impact score, and Child and Adolescent Gilles de la Tourette Syndrome–Quality of Life Activities of Daily Living subscale score in the deutetrabenazine high-dose and low-dose groups compared with placebo at the end of the titration period.
A total of 34 participants (65%) reported treatment-emergent adverse events in the high-dose deutetrabenazine group, 24 (44%) in the low-dose deutetrabenazine group, and 25 (49%) in the placebo group, most of which were mild or moderate in severity. No deaths occurred.
The researchers noted that a majority of participants were non-Hispanic White, and therefore their findings could not be generalized to more diverse populations.
“The primary efficacy endpoint was not met, despite a numeric improvement at the end of the titration period,” concluded the researchers. “Secondary efficacy endpoint results were generally similar to the primary endpoint. Deutetrabenazine was generally well tolerated in this 8-week study.”
Disclosure: This study was funded by Teva Pharmaceutical Industries Ltd, Petach Tikva, Israel, in partnership with Nuvelution TS Pharma. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Coffey BS, Jankovic J, Claassen DO, et al. Efficacy and safety of fixed-dose deutetrabenazine in children and adolescents for tics associated with Tourette syndrome: a randomized clinical trial. JAMA Netw Open. Published online October 18, 2021. doi: 10.1001/jamanetworkopen.2021.29397
Source: Medical Bag https://www.medicalbag.com/home/specialties/pediatrics/deutetrabenazine-placebo-tics-tourette-syndrome-pediatric-patients/