Background BN82451B is a small, orally active molecule with good CNS penetration. Preclinical studies in tgHD R6/2 mice suggested improved motor function and prolonged survival. In addition antidyskinetic activity was observed in other models. The proposed mechanisms of action (MOA) are (1) antiexcytotoxic due to a sodium channel blocking potential, (2) antioxidant, (3) anti-inflammatory due to a cyclooxygenase (COX) inhibitory potential and (4) mitochondrial protective.
Aims The primary objective of this phase 2a study (NCT02231580) is to investigate the safety and tolerability of BN82451B bid versus placebo for 28 days in male HD subjects. Secondary objectives include assessment of pharmacokinetics and of pharmacodynamics via the effects on quantitative motor (Q-Motor) measures. UHDRS subscales are implemented as exploratory measures.
Methods Subjects: We intend to recruit 30 male HD subjects. 24 receive BN82451B and 6 placebo. The study is conducted in an inpatient setting at a single phase I unit in Germany.
Design A sequential design was chosen to enable dose escalation starting with 40 mg bid with a potential maximum dose of 80 mg bid. Three subsequent cohorts of 10 patients each are randomised with different starting doses. Subjects in group one are treated with 40 mg bid for 14 days and may be increased to 60 mg bid the subsequent 14 days. In group 2, subjects may first receive 60 mg bid with possible increase to 80 mg bid. Group 3 subjects may receive 80 mg bid for 28 days. Dose increases in the consecutive groups are subject to approval by a Data Review Committee (DRC). The decision to increase the dose in individual patient will be based on the investigator’s judgement.
Results Results of the study are expected for Q4/2016.
Conclusions Recruitment in this trial is difficult as in-patient periods of nearly one month are logistically challenging. Safety data will be available soon and pharmacodynamics readouts such as Q-motor measures may help to guide decisions on the further path of development of BN82451B.
- clinical trial
- phase II