Tags

Type your tag names separated by a space and hit enter

NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study.
Mov Disord. 2015 Oct; 30(12):1681-7.MD

Abstract

BACKGROUND

Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI-98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6-week, double-blind, placebo-controlled, dose-titration study evaluating the safety, tolerability, and efficacy of NBI-98854 for the treatment of tardive dyskinesia.

METHODS

Male and female adult subjects with moderate or severe tardive dyskinesia were included. NBI-98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment. The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded, central video raters. The secondary endpoint was the Clinical Global Impression of Change-Tardive Dyskinesia score assessed by the blinded investigator.

RESULTS

Two hundred five potential subjects were screened, and 102 were randomized; 76% of NBI-98854 subjects and 80% of placebo subjects reached the maximum allowed dose. Abnormal Involuntary Movement Scale scores for NBI-98854 compared with placebo were significantly reduced (p = 0.0005). Active drug was also superior on the Clinical Global Impression of Change-Tardive Dyskinesia (p < 0.0001). Treatment-emergent adverse event rates were 49% in the NBI-98854 and 33% in the placebo subjects. The most common adverse events (active vs. placebo) were fatigue and headache (9.8% vs. 4.1%) and constipation and urinary tract infection (3.9% vs. 6.1%). No clinically relevant changes in safety assessments were noted.

CONCLUSION

NBI-98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI-98854 now underway.

Authors+Show Affiliations

Neurocrine Biosciences, San Diego, California, USA.Neurocrine Biosciences, San Diego, California, USA.University of South Florida, Tampa, Florida, USA.Emory University, Atlanta, Georgia, USA.Neurocrine Biosciences, San Diego, California, USA.Biscayne Bay Institute, Miami, Florida, USA.Research in Miami, Miami, Florida, USA.

Pub Type(s)

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

Language

eng

PubMed ID

26346941

Citation

O'Brien, Christopher F., et al. "NBI-98854, a Selective Monoamine Transport Inhibitor for the Treatment of Tardive Dyskinesia: a Randomized, Double-blind, Placebo-controlled Study." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 30, no. 12, 2015, pp. 1681-7.
O'Brien CF, Jimenez R, Hauser RA, et al. NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Mov Disord. 2015;30(12):1681-7.
O'Brien, C. F., Jimenez, R., Hauser, R. A., Factor, S. A., Burke, J., Mandri, D., & Castro-Gayol, J. C. (2015). NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Movement Disorders : Official Journal of the Movement Disorder Society, 30(12), 1681-7. https://doi.org/10.1002/mds.26330
O'Brien CF, et al. NBI-98854, a Selective Monoamine Transport Inhibitor for the Treatment of Tardive Dyskinesia: a Randomized, Double-blind, Placebo-controlled Study. Mov Disord. 2015;30(12):1681-7. PubMed PMID: 26346941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. AU - O'Brien,Christopher F, AU - Jimenez,Roland, AU - Hauser,Robert A, AU - Factor,Stewart A, AU - Burke,Joshua, AU - Mandri,Daniel, AU - Castro-Gayol,Julio C, Y1 - 2015/09/08/ PY - 2015/03/04/received PY - 2015/06/08/revised PY - 2015/06/13/accepted PY - 2015/9/9/entrez PY - 2015/9/9/pubmed PY - 2016/7/28/medline KW - antipsychotic drugs KW - randomized controlled trial KW - tardive dyskinesia KW - vesicular monoamine transporter (VMAT2) SP - 1681 EP - 7 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 30 IS - 12 N2 - BACKGROUND: Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI-98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6-week, double-blind, placebo-controlled, dose-titration study evaluating the safety, tolerability, and efficacy of NBI-98854 for the treatment of tardive dyskinesia. METHODS: Male and female adult subjects with moderate or severe tardive dyskinesia were included. NBI-98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment. The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded, central video raters. The secondary endpoint was the Clinical Global Impression of Change-Tardive Dyskinesia score assessed by the blinded investigator. RESULTS: Two hundred five potential subjects were screened, and 102 were randomized; 76% of NBI-98854 subjects and 80% of placebo subjects reached the maximum allowed dose. Abnormal Involuntary Movement Scale scores for NBI-98854 compared with placebo were significantly reduced (p = 0.0005). Active drug was also superior on the Clinical Global Impression of Change-Tardive Dyskinesia (p < 0.0001). Treatment-emergent adverse event rates were 49% in the NBI-98854 and 33% in the placebo subjects. The most common adverse events (active vs. placebo) were fatigue and headache (9.8% vs. 4.1%) and constipation and urinary tract infection (3.9% vs. 6.1%). No clinically relevant changes in safety assessments were noted. CONCLUSION: NBI-98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI-98854 now underway. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/26346941/NBI_98854_a_selective_monoamine_transport_inhibitor_for_the_treatment_of_tardive_dyskinesia:_A_randomized_double_blind_placebo_controlled_study_ L2 - https://doi.org/10.1002/mds.26330 DB - PRIME DP - Unbound Medicine ER -