OBJECTIVES : Once-daily valbenazine is approved for tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to dopamine receptor blocking agents (e.g., antipsychotics). This Phase 4, double-blind, placebo-controlled, withdrawal study (NCT03891862) was conducted to assess the persistence of valbenazine effect in patients with TD.

METHODS : Study participants received open-label valbenazine (VBZ-OL) for 8 weeks, with dosing initiated at 40 mg and escalated to 80 mg after 1 week (dose reduction allowed for tolerability). After VBZ-OL, participants were randomized (1:1) to receive placebo (VBZ/PBO) or continue taking the same valbenazine dose (VBZ/VBZ). Assessments were conducted at study baseline, Week 8 (end of VBZ-OL, randomization baseline), and Week 16 (end of withdrawal). Abnormal Involuntary Movement Scale (AIMS) total score was used to assess persistence of effect. Patient-reported outcomes included EuroQoL’s 5-Dimension 5-Level questionnaire (EQ-5D-5L) and the Sheehan Disability Scale (SDS). Mean values are presented with standard errors.

RESULTS : Persistence of effect was analyzed in 117 randomized participants (placebo=58; valbenazine=59). Mean changes from study baseline to Week 8 in AIMS total score indicated improvements with VBZ-OL. Changes from Week 8 to Week 16 indicated initial loss of valbenazine effect after treatment withdrawal: VBZ/PBO, 0.7±0.7; VBZ/VBZ, -1.7±0.4. However, mean changes from study baseline to Week 16 suggested some overall persistence of valbenazine effect: VBZ/PBO, -3.2±0.7; VBZ/VBZ, -5.5±0.6. Mean improvements from study baseline to Week 16 for health-related quality of life (EQ-5D-5L) and functional status (SDS) were greater in patients who continued taking valbenazine. 32.6% of all participants had ≥1 TEAE with VBZ-OL; 32.2% (VBZ/PBO) and 23.7% (VBZ/VBZ) had ≥1 TEAE during randomized withdrawal.

CONCLUSIONS : Valbenazine effects diminished after treatment withdrawal, but some overall persistence of effect was observed. Overall mean improvements in TD movements, quality of life, and functioning were greater in patients who continued receiving once-daily valbenazine.