Study Exploring Safety, Pharmacokinetic and Pharmacodynamic of BN82451 in Male Huntington's Disease Patients
Condition: Huntington's Disease
MeSH terms: Huntington Disease
Intervention: BN82451B; Placebo
Intervention description: BN82451B capsule; Placebo capsule
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 17.0
Sex: Male
Minimum age: 20 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Neurodegenerative genetic disorder

Summary:

      The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and
      pharmacodynamics of BN82451B versus placebo after oral administration twice daily (bid) for
      28 days in patients with Huntington's Disease (HD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male subjects 20 to 70 years old (inclusive).

          -  Provision of written informed consent prior to any study related procedures. In this
             study consent may be provided by the legal guardian or carer.

          -  Confirmed symptomatic Huntington's Disease diagnosed based on clinical features (i.e.
             Diagnostic Confidence Level equal to 4) and presence of at least 36 cytosine adenine
             guanine (CAG) repeats in the Huntington gene as documented by a copy of a previous
             genetic test report.

          -  Unified Huntington's Disease Rated Scale-Total Motor Score (UDHRS-TMS) greater than or
             equal to 15.

          -  Ambulatory.

          -  UDHRS-Total Functional Capacity (TFC) greater than or equal to 3 (i.e. Shoulson & Fahn
             Scale stages 1-3 inclusive.

          -  Subjects on antipsychotic, antidepressant, anxiolytic and hypnotic therapy must have
             been on stable treatment 4 weeks prior to study drug start and during the study
             period.

          -  Able to swallow study medication.

          -  Able to perform Q-Motor tests.

          -  If his partner is at risk of pregnancy, the subject agrees to use a condom or be
             abstinent for 14 days after the last intake of study drug.

        Exclusion Criteria:

          -  Juvenile forms of Huntington's Disease.

          -  Any form of chorea other than Huntington's Disease.

          -  History of seizure, epilepsy or other convulsive disorder, with the exception of
             febrile seizures in childhood.

          -  History of conditions susceptible to induce seizures such as severe traumatic brain
             injury, brain tumours, stroke.

          -  History of neurosurgical procedure.

          -  Current evidence or history (within 1 year of Baseline) of psychosis, hallucinations
             or delusions, including major depression with psychotic features, as defined in the
             Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR). Patients
             currently experiencing mild depression, or moderate depression which is adequately and
             appropriately treated in the judgement of the investigator, can participate if
             depression is not expected to interfere with study participation.

          -  History of drug and/or alcohol abuse as per the DSM IV-TR criteria within 12 months
             prior to Baseline.

          -  At imminent risk of self harm based on investigator's clinical judgment, with a "yes"
             answer on item 4 or 5 on the Columbia-Suicide Severity Rating Scale (CSSRS)
             questionnaire.

          -  Mini Mental State Exam (MMSE) total score less than or equal to 23.

          -  Used any investigational drugs within 30 days prior to Screening or 5 half lives,
             whichever is the longest.

          -  Known allergy/sensitivity to the study drugs or their excipients.

          -  A severe or ongoing unstable medical condition (e.g. cardiac, hepatic, renal,
             metabolic or endocrine).

          -  Any clinically significant condition which, in the opinion of the investigator, would
             interfere with the trial evaluations or optimal participation in the trial.

          -  Any significant laboratory results which, in the investigator's opinion, would not be
             compatible with study participation or represent a risk for subjects while in the
             study.

          -  History of malignant disease within the 5 years prior to Screening (with the exception
             of basal cell and squamous cell carcinomas of the skin that have been completely
             excised, in situ prostate cancer with a normal prostate specific antigen).

          -  An estimated Creatinine Clearance (CrCl) of less than 60 mL/minute (using the
             Cockcroft-Gault formula).

          -  Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) values greater than or
             equal to 2 times the Upper Limit of Normal range (ULN) or both GGT and ALT values
             greater than three times the ULN.

          -  Known history of hepatitis B or C or Human Immunodeficiency Virus (HIV) or positive
             serology at Screening.

          -  Corrected QT interval using Bazett's correction (QTcB) greater than 450 ms or other
             clinically significant ECG findings.

          -  Receiving tetrabenazine within 4 weeks prior to Baseline.

          -  Taking the following prohibited medications/substances: Strong Cytochrome (CYP) 3A4
             inhibitors and Strong CYP3A4 inducers (Wash out prior to Baseline 30 days or 5 half
             lives,whichever is the longest), CYP2B6 substrates, CYP1A2 substrates, CYP3A4
             substrates, CYP2C19 substrates (assessed on a case by case basis)