PMID- 28839341 OWN - NLM STAT- MEDLINE DCOM- 20190625 LR - 20220330 IS - 0048-5764 (Print) IS - 2472-2448 (Electronic) IS - 0048-5764 (Linking) VI - 47 IP - 3 DP - 2017 Aug 1 TI - Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. PG - 61-68 AB - 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-Asberg 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). FAU - Josiassen, Richard C AU - Josiassen RC AD - 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. FAU - Kane, John M AU - Kane JM AD - 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. FAU - Liang, Grace S AU - Liang GS AD - 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. FAU - Burke, Joshua AU - Burke J AD - 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. FAU - O'Brien, Christopher F AU - O'Brien CF AD - 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. LA - eng SI - ClinicalTrials.gov/NCT01688037 SI - ClinicalTrials.gov/NCT02274558 SI - ClinicalTrials.gov/NCT02405091 PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Psychopharmacol Bull JT - Psychopharmacology bulletin JID - 0101123 RN - 0 (Adrenergic Uptake Inhibitors) RN - 0 (Antipsychotic Agents) RN - 0 (SLC18A2 protein, human) RN - 0 (Vesicular Monoamine Transport Proteins) RN - 54K37P50KH (valbenazine) RN - HG18B9YRS7 (Valine) RN - Z9O08YRN8O (Tetrabenazine) SB - IM MH - Adrenergic Uptake Inhibitors/*adverse effects MH - Adult MH - Aged MH - Antipsychotic Agents/adverse effects MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Humans MH - *Long Term Adverse Effects MH - Male MH - Middle Aged MH - Mood Disorders/*drug therapy MH - *Outcome Assessment, Health Care MH - Psychotic Disorders/*drug therapy MH - Schizophrenia/*drug therapy MH - Tardive Dyskinesia/chemically induced/*drug therapy MH - Tetrabenazine/adverse effects/*analogs & derivatives MH - Valine/adverse effects/*analogs & derivatives MH - Vesicular Monoamine Transport Proteins/*antagonists & inhibitors PMC - PMC5546552 OTO - NOTNLM OT - antipsychotic agents OT - bipolar disorder OT - depression OT - double-blind method OT - mood disorders OT - psychiatric status rating scales OT - psychopathology OT - psychopharmacology OT - psychotic disorders OT - schizophrenia OT - tardive dyskinesia OT - valbenazine EDAT- 2017/08/26 06:00 MHDA- 2019/06/27 06:00 PMCR- 2017/08/01 CRDT- 2017/08/26 06:00 PHST- 2017/08/26 06:00 [entrez] PHST- 2017/08/26 06:00 [pubmed] PHST- 2019/06/27 06:00 [medline] PHST- 2017/08/01 00:00 [pmc-release] PST - ppublish SO - Psychopharmacol Bull. 2017 Aug 1;47(3):61-68.