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Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials.
Drug Saf. 2018 04; 41(4):429-440.DS

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.

Authors+Show Affiliations

Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA, 92130, USA. dthai@neurocrine.com.Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA, 92130, USA.Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA, 92130, USA.Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA, 92130, USA.Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA, 92130, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29218680

Citation

Thai-Cuarto, Dao, et al. "Cardiovascular Profile of Valbenazine: Analysis of Pooled Data From Three Randomized, Double-Blind, Placebo-Controlled Trials." Drug Safety, vol. 41, no. 4, 2018, pp. 429-440.
Thai-Cuarto D, O'Brien CF, Jimenez R, et al. Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials. Drug Saf. 2018;41(4):429-440.
Thai-Cuarto, D., O'Brien, C. F., Jimenez, R., Liang, G. S., & Burke, J. (2018). Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials. Drug Safety, 41(4), 429-440. https://doi.org/10.1007/s40264-017-0623-1
Thai-Cuarto D, et al. Cardiovascular Profile of Valbenazine: Analysis of Pooled Data From Three Randomized, Double-Blind, Placebo-Controlled Trials. Drug Saf. 2018;41(4):429-440. PubMed PMID: 29218680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials. AU - Thai-Cuarto,Dao, AU - O'Brien,Christopher F, AU - Jimenez,Roland, AU - Liang,Grace S, AU - Burke,Joshua, PY - 2017/12/9/pubmed PY - 2018/10/3/medline PY - 2017/12/9/entrez SP - 429 EP - 440 JF - Drug safety JO - Drug Saf VL - 41 IS - 4 N2 - 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. SN - 1179-1942 UR - https://www.unboundmedicine.com/medline/citation/29218680/Cardiovascular_Profile_of_Valbenazine:_Analysis_of_Pooled_Data_from_Three_Randomized_Double_Blind_Placebo_Controlled_Trials_ L2 - https://dx.doi.org/10.1007/s40264-017-0623-1 DB - PRIME DP - Unbound Medicine ER -