J07 What can we learn from a phase ii study with BN82451B in hd beyond safety and tolerability – clinical versus objective motor measures. (September 2018)

• Record Type: Journal Article
• Authors: Bohlen, Stefan; Paty, Isabelle; Volteau, Magali; Meyer, Ingo; Rein, Werner; Kosinski, Christoph; Reilmann, Ralf
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 89(2018)Supplement 1
• Page Start: A100
• Page End: A100
• Publication Date: 2018-09
• Subjects: phase II clinical trial -- Q-motor -- clinical rating scale; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2018-EHDN.267
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Preclinical research indicates that BN82451B has potential to interfere with excitotoxicity, and possesses antioxidant, anti-inflammatory, and mitochondrial protection properties. In-vivo studies in tgHD mice suggested neuroprotective and antidyskinetic effects. Aims: The safety and tolerability of BN82451B was tested in Huntington's Disease (HD) alongside exploratory efficacy with a focus on motor symptoms. Methods: This 4-week, randomized, placebo-controlled, double-blind, in-patient, proof-of-concept study explored escalating doses (40 – 80 mg BID) of BN82451B in symptomatic HD subjects. Primary objective was safety and tolerability, secondary objectives were motor symptoms assessed by Q-Motor and the UHDRS-TMS. Results: A total of 30 subjects were planned to be included, but the study was terminated after inclusion of 17 subjects (14 BN82451B/3 placebo). Recruitment in this study was complicated by an obligatory in-patient setting at a phase-1 research-unit for four weeks. There were no severe safety issues, but 6 of the 14 treated subjects (43%) developed cutaneous adverse events (rash) which led to discontinuation of treatment in 3 cases and resolved after discontinuation of treatment in all 6 cases. Another 2 subjects were withdrawn due to nausea and vomiting. BN82451B treatment did not differentiate from placebo in the exploratory outcome variables. While placebo subjects showed a mean improvement in the UHDRS-TMS, Q-Motor measures indicated no change in the placebo group. However, mean Q-Motor changes of BN82451B treated patients suggested a none-significant deterioration of motor performance while on drug, which reverted after drug discontinuation. Conclusions: BN82451B induced skin rash in 43% of exposed patients and increased nausea/vomiting. Exploratory analysis did suggest a potential for deterioration of motor symptoms in HD subjects under treatment. Q-Motor measures showed much less variance and no placebo response in repeated assessments compared to the UHDRS-TMS. It was decided to discontinue the study.