Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials

Drug Saf. 2018 Apr;41(4):429-440. doi: 10.1007/s40264-017-0623-1.

Abstract

Introduction: Valbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults.

Objective: Using data from double-blind, placebo-controlled trials, analyses were conducted to evaluate the cardiovascular effects of once-daily valbenazine in patients with a psychiatric disorder who developed tardive dyskinesia after exposure to a dopamine-blocking medication.

Methods: Data were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related treatment-emergent adverse events, vital sign measurements, and electrocardiogram parameters.

Results: The pooled safety population included 400 participants (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n = 112). A history of cardiac disorders was present in 11.8% of participants, and 74.3% were taking a concomitant medication with known potential for QT prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, - 2.1, - 1.8 mmHg), diastolic blood pressure (- 0.1, - 1.6, - 1.2 mmHg), heart rate (- 1.7, - 2.2, - 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine vs. placebo. No statistically significant differences were observed between placebo and valbenazine in cardiovascular-related, treatment-emergent adverse events. No notable additional effects on cardiovascular outcomes were found with up to 48 weeks of valbenazine treatment.

Conclusions: Results from double-blind, placebo-controlled trials showed no apparent difference between valbenazine and placebo on cardiovascular outcomes. No additional cardiovascular risk was detected during a longer extension study with valbenazine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular System / drug effects*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Female
  • Heart Rate / drug effects
  • Humans
  • Middle Aged
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic
  • Tardive Dyskinesia / drug therapy
  • Tetrabenazine / adverse effects
  • Tetrabenazine / analogs & derivatives*
  • Tetrabenazine / therapeutic use
  • Valine / adverse effects
  • Valine / analogs & derivatives*
  • Valine / therapeutic use

Substances

  • valbenazine
  • Valine
  • Tetrabenazine