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Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder.
Psychopharmacol Bull. 2017 08 01; 47(3):53-60.PB

Abstract

BACKGROUND

Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment.

METHODS

KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes.

RESULTS

Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40 mg, 2.9, d = 0.39; PBO, 3.2), Week 48 (80 mg, 2.0; 40 mg, 2.2), Week 52 (80 mg, 3.6; 40 mg, 2.8). AIMS responder rates (≥50% score reduction) were greater with VBZ vs PBO at Week 6 (80 mg, 38.5%, NNT = 4; 40 mg, 19.0%, NNT = 9; PBO, 7.7%), were increased at Week 48 (80 mg, 56.0%; 40 mg, 33.3%), and lower after VBZ washout (Week 52 80 mg, 16.7%; 40 mg, 27.8%). CGI-TD responder rates followed a similar pattern: Week 6 (80 mg, 34.6%, NNT = 6; 40 mg, 28.6%, NNT = 8; PBO, 15.4%), Week 48 (80 mg, 80.0%; 40 mg, 61.1%), Week 52 (80 mg, 25.0%; 40 mg, 44.4%).

CONCLUSION

Sustained TD improvements were found in subjects with a mood disorder who received up to 48 weeks of VBZ, with TD reverting toward baseline severity when assessed 4 weeks after treatment withdrawal. Together with results from SCHZ subjects and the long-term safety profile (presented separately), these results indicate that long-term VBZ can be beneficial for managing TD regardless of psychiatric diagnosis.

Authors+Show Affiliations

Dr. Correll, Hofstra Northwell School of Medicine, Hempstead, NY; Dr. Josiassen, Translational Neuroscience, Conshohocken, PA; Drs. Liang, Burke, O'Brien, Neurocrine Biosciences, Inc., San Diego, CA.Dr. Correll, Hofstra Northwell School of Medicine, Hempstead, NY; Dr. Josiassen, Translational Neuroscience, Conshohocken, PA; Drs. Liang, Burke, O'Brien, Neurocrine Biosciences, Inc., San Diego, CA.Dr. Correll, Hofstra Northwell School of Medicine, Hempstead, NY; Dr. Josiassen, Translational Neuroscience, Conshohocken, PA; Drs. Liang, Burke, O'Brien, Neurocrine Biosciences, Inc., San Diego, CA.Dr. Correll, Hofstra Northwell School of Medicine, Hempstead, NY; Dr. Josiassen, Translational Neuroscience, Conshohocken, PA; Drs. Liang, Burke, O'Brien, Neurocrine Biosciences, Inc., San Diego, CA.Dr. Correll, Hofstra Northwell School of Medicine, Hempstead, NY; Dr. Josiassen, Translational Neuroscience, Conshohocken, PA; Drs. Liang, Burke, O'Brien, Neurocrine Biosciences, Inc., San Diego, CA.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28839340

Citation

Correll, Christoph U., et al. "Efficacy of Valbenazine (NBI-98854) in Treating Subjects With Tardive Dyskinesia and Mood Disorder." Psychopharmacology Bulletin, vol. 47, no. 3, 2017, pp. 53-60.
Correll CU, Josiassen RC, Liang GS, et al. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder. Psychopharmacol Bull. 2017;47(3):53-60.
Correll, C. U., Josiassen, R. C., Liang, G. S., Burke, J., & O'Brien, C. F. (2017). Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder. Psychopharmacology Bulletin, 47(3), 53-60.
Correll CU, et al. Efficacy of Valbenazine (NBI-98854) in Treating Subjects With Tardive Dyskinesia and Mood Disorder. Psychopharmacol Bull. 2017 08 1;47(3):53-60. PubMed PMID: 28839340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder. AU - Correll,Christoph U, AU - Josiassen,Richard C, AU - Liang,Grace S, AU - Burke,Joshua, AU - O'Brien,Christopher F, PY - 2017/8/26/entrez PY - 2017/8/26/pubmed PY - 2019/6/27/medline KW - amines KW - antipsychotic agents KW - double-blind method KW - mood disorders KW - psychopharmacology KW - psychotic disorders KW - schizophrenia KW - tardive dyskinesia KW - valbenazine SP - 53 EP - 60 JF - Psychopharmacology bulletin JO - Psychopharmacol Bull VL - 47 IS - 3 N2 - BACKGROUND: Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. METHODS: KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. RESULTS: Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40 mg, 2.9, d = 0.39; PBO, 3.2), Week 48 (80 mg, 2.0; 40 mg, 2.2), Week 52 (80 mg, 3.6; 40 mg, 2.8). AIMS responder rates (≥50% score reduction) were greater with VBZ vs PBO at Week 6 (80 mg, 38.5%, NNT = 4; 40 mg, 19.0%, NNT = 9; PBO, 7.7%), were increased at Week 48 (80 mg, 56.0%; 40 mg, 33.3%), and lower after VBZ washout (Week 52 80 mg, 16.7%; 40 mg, 27.8%). CGI-TD responder rates followed a similar pattern: Week 6 (80 mg, 34.6%, NNT = 6; 40 mg, 28.6%, NNT = 8; PBO, 15.4%), Week 48 (80 mg, 80.0%; 40 mg, 61.1%), Week 52 (80 mg, 25.0%; 40 mg, 44.4%). CONCLUSION: Sustained TD improvements were found in subjects with a mood disorder who received up to 48 weeks of VBZ, with TD reverting toward baseline severity when assessed 4 weeks after treatment withdrawal. Together with results from SCHZ subjects and the long-term safety profile (presented separately), these results indicate that long-term VBZ can be beneficial for managing TD regardless of psychiatric diagnosis. SN - 0048-5764 UR - https://www.unboundmedicine.com/medline/citation/28839340/Efficacy_of_Valbenazine__NBI_98854__in_Treating_Subjects_with_Tardive_Dyskinesia_and_Mood_Disorder_ L2 - https://medworksmedia.com/product/psychopharmacology-47-3-correll/ DB - PRIME DP - Unbound Medicine ER -