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Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder.
Psychopharmacol Bull. 2017 08 01; 47(3):61-68.PB

Abstract

BACKGROUND

The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD.

METHODS

The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively.

RESULTS

The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that psychiatric stability was maintained in the SCHZ subgroup (PANSS Total, -3.4; PANSS Positive, -1.1; PANSS Negative, -0.1; PANSS General Psychopathology, -2.2; CDSS total, -0.4) and the mood subgroup (MADRS Total, 0.0; YMRS Total, -1.2). These scores remained generally stable during the 4-week drug-free follow-up periods. In the LTE population, mean changes in laboratory parameters, vital signs, ECG, and EPS scales were generally minimal and not clinically significant.

CONCLUSION

Valbenazine appeared to be well tolerated in adults with TD who received up to 48 weeks of treatment. In addition to long-term efficacy results (presented separately), these results suggest that valbenazine may be appropriate for the long-term management of TD regardless of underlying psychiatric diagnosis (SCHZ disorder or mood disorder).

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28839341

Citation

Josiassen, Richard C., et al. "Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects With Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder." Psychopharmacology Bulletin, vol. 47, no. 3, 2017, pp. 61-68.
Josiassen RC, Kane JM, Liang GS, et al. Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. Psychopharmacol Bull. 2017;47(3):61-68.
Josiassen, R. C., Kane, J. M., Liang, G. S., Burke, J., & O'Brien, C. F. (2017). Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. Psychopharmacology Bulletin, 47(3), 61-68.
Josiassen RC, et al. Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects With Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. Psychopharmacol Bull. 2017 08 1;47(3):61-68. PubMed PMID: 28839341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. AU - Josiassen,Richard C, AU - Kane,John M, 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 - antipsychotic agents KW - bipolar disorder KW - depression KW - double-blind method KW - mood disorders KW - psychiatric status rating scales KW - psychopathology KW - psychopharmacology KW - psychotic disorders KW - schizophrenia KW - tardive dyskinesia KW - valbenazine SP - 61 EP - 68 JF - Psychopharmacology bulletin JO - Psychopharmacol Bull VL - 47 IS - 3 N2 - BACKGROUND: The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD. METHODS: The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively. RESULTS: The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that psychiatric stability was maintained in the SCHZ subgroup (PANSS Total, -3.4; PANSS Positive, -1.1; PANSS Negative, -0.1; PANSS General Psychopathology, -2.2; CDSS total, -0.4) and the mood subgroup (MADRS Total, 0.0; YMRS Total, -1.2). These scores remained generally stable during the 4-week drug-free follow-up periods. In the LTE population, mean changes in laboratory parameters, vital signs, ECG, and EPS scales were generally minimal and not clinically significant. CONCLUSION: Valbenazine appeared to be well tolerated in adults with TD who received up to 48 weeks of treatment. In addition to long-term efficacy results (presented separately), these results suggest that valbenazine may be appropriate for the long-term management of TD regardless of underlying psychiatric diagnosis (SCHZ disorder or mood disorder). SN - 0048-5764 UR - https://www.unboundmedicine.com/medline/citation/28839341/Long_Term_Safety_and_Tolerability_of_Valbenazine__NBI_98854__in_Subjects_with_Tardive_Dyskinesia_and_a_Diagnosis_of_Schizophrenia_or_Mood_Disorder_ L2 - https://medworksmedia.com/product/psychopharmacology-47-3-josiassen/ DB - PRIME DP - Unbound Medicine ER -