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KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia.
Am J Psychiatry. 2017 05 01; 174(5):476-484.AJ

Abstract

OBJECTIVE

Tardive dyskinesia is a persistent movement disorder induced by dopamine receptor blockers, including antipsychotics. Valbenazine (NBI-98854) is a novel, highly selective vesicular monoamine transporter 2 inhibitor that demonstrated favorable efficacy and tolerability in the treatment of tardive dyskinesia in phase 2 studies. This phase 3 study further evaluated the efficacy, safety, and tolerability of valbenazine as a treatment for tardive dyskinesia.

METHOD

This 6-week, randomized, double-blind, placebo-controlled trial included patients with schizophrenia, schizoaffective disorder, or a mood disorder who had moderate or severe tardive dyskinesia. Participants were randomly assigned in a 1:1:1 ratio to once-daily placebo, valbenazine at 40 mg/day, or valbenazine at 80 mg/day. The primary efficacy endpoint was change from baseline to week 6 in the 80 mg/day group compared with the placebo group on the Abnormal Involuntary Movement Scale (AIMS) dyskinesia score (items 1-7), as assessed by blinded central AIMS video raters. Safety assessments included adverse event monitoring, laboratory tests, ECG, and psychiatric measures.

RESULTS

The intent-to-treat population included 225 participants, of whom 205 completed the study. Approximately 65% of participants had schizophrenia or schizoaffective disorder, and 85.5% were receiving concomitant antipsychotics. Least squares mean change from baseline to week 6 in AIMS dyskinesia score was -3.2 for the 80 mg/day group, compared with -0.1 for the placebo group, a significant difference. AIMS dyskinesia score was also reduced in the 40 mg/day group (-1.9 compared with -0.1). The incidence of adverse events was consistent with previous studies.

CONCLUSIONS

Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was generally well tolerated, and psychiatric status remained stable. Longer trials are necessary to understand the long-term effects of valbenazine in patients with tardive dyskinesia.

Authors+Show Affiliations

From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.From the Departments of Neurology and Molecular Pharmacology and Physiology, University of South Florida, Tampa; the Department of Neurology, Emory University, Atlanta; the Department of Psychiatry, University of California, Los Angeles; University Hills Clinical Research, Irving, Tex.; the Department of Psychology, Long Island University, New York; and Neurocrine Biosciences, Inc., San Diego.

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28320223

Citation

Hauser, Robert A., et al. "KINECT 3: a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia." The American Journal of Psychiatry, vol. 174, no. 5, 2017, pp. 476-484.
Hauser RA, Factor SA, Marder SR, et al. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017;174(5):476-484.
Hauser, R. A., Factor, S. A., Marder, S. R., Knesevich, M. A., Ramirez, P. M., Jimenez, R., Burke, J., Liang, G. S., & O'Brien, C. F. (2017). KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. The American Journal of Psychiatry, 174(5), 476-484. https://doi.org/10.1176/appi.ajp.2017.16091037
Hauser RA, et al. KINECT 3: a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017 05 1;174(5):476-484. PubMed PMID: 28320223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. AU - Hauser,Robert A, AU - Factor,Stewart A, AU - Marder,Stephen R, AU - Knesevich,Mary Ann, AU - Ramirez,Paul M, AU - Jimenez,Roland, AU - Burke,Joshua, AU - Liang,Grace S, AU - O'Brien,Christopher F, Y1 - 2017/03/21/ PY - 2017/3/23/pubmed PY - 2017/6/20/medline PY - 2017/3/22/entrez KW - Antipsychotics KW - Movement Disorder KW - Tardive Dyskinesia KW - Valbenazine KW - Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor SP - 476 EP - 484 JF - The American journal of psychiatry JO - Am J Psychiatry VL - 174 IS - 5 N2 - OBJECTIVE: Tardive dyskinesia is a persistent movement disorder induced by dopamine receptor blockers, including antipsychotics. Valbenazine (NBI-98854) is a novel, highly selective vesicular monoamine transporter 2 inhibitor that demonstrated favorable efficacy and tolerability in the treatment of tardive dyskinesia in phase 2 studies. This phase 3 study further evaluated the efficacy, safety, and tolerability of valbenazine as a treatment for tardive dyskinesia. METHOD: This 6-week, randomized, double-blind, placebo-controlled trial included patients with schizophrenia, schizoaffective disorder, or a mood disorder who had moderate or severe tardive dyskinesia. Participants were randomly assigned in a 1:1:1 ratio to once-daily placebo, valbenazine at 40 mg/day, or valbenazine at 80 mg/day. The primary efficacy endpoint was change from baseline to week 6 in the 80 mg/day group compared with the placebo group on the Abnormal Involuntary Movement Scale (AIMS) dyskinesia score (items 1-7), as assessed by blinded central AIMS video raters. Safety assessments included adverse event monitoring, laboratory tests, ECG, and psychiatric measures. RESULTS: The intent-to-treat population included 225 participants, of whom 205 completed the study. Approximately 65% of participants had schizophrenia or schizoaffective disorder, and 85.5% were receiving concomitant antipsychotics. Least squares mean change from baseline to week 6 in AIMS dyskinesia score was -3.2 for the 80 mg/day group, compared with -0.1 for the placebo group, a significant difference. AIMS dyskinesia score was also reduced in the 40 mg/day group (-1.9 compared with -0.1). The incidence of adverse events was consistent with previous studies. CONCLUSIONS: Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was generally well tolerated, and psychiatric status remained stable. Longer trials are necessary to understand the long-term effects of valbenazine in patients with tardive dyskinesia. SN - 1535-7228 UR - https://www.unboundmedicine.com/medline/citation/28320223/KINECT_3:_A_Phase_3_Randomized_Double_Blind_Placebo_Controlled_Trial_of_Valbenazine_for_Tardive_Dyskinesia_ L2 - https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2017.16091037?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -