Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials
| Autor: | Christopher F. O'Brien, Dao Thai-Cuarto, Joshua Burke, Grace S. Liang, Roland Jimenez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions Population Tetrabenazine Blood Pressure Toxicology Tardive dyskinesia Placebo QT interval Cardiovascular System 03 medical and health sciences 0302 clinical medicine Clinical Trials Phase II as Topic Double-Blind Method Heart Rate Internal medicine Medicine Humans Multicenter Studies as Topic Tardive Dyskinesia Pharmacology (medical) Valbenazine Original Research Article education Adverse effect Aged Randomized Controlled Trials as Topic Pharmacology education.field_of_study Dose-Response Relationship Drug business.industry Valine Middle Aged medicine.disease 030227 psychiatry Clinical trial Blood pressure Clinical Trials Phase III as Topic Cardiovascular Diseases Female business 030217 neurology & neurosurgery |
| Zdroj: | Drug Safety |
| ISSN: | 1179-1942 0114-5916 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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