Huntington's disease MedDRA version: 18.1 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: BN8251B
Pharmaceutical Form: Capsule
INN or Proposed INN: N/A
CAS Number: 918656-59-4
Current Sponsor code: BN82451B
Other descriptive name: BN82451B
Concentration unit: mg milligram(s)
Sponsors
Ipsen Pharma
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: (1) Male subjects = 20 to = 70 years old. (2) Provision of written informed consent prior to any study related procedures. (3) Confirmed symptomatic HD diagnosed based on clinical features (i.e. Diagnostic Confidence Level = 4) and presence of = 36 CAG repeats in the Huntington gene as documented by a copy of a previous genetic test report. (4) UDHRS-TMS = 15. (5) Ambulatory. (6) UHDRS-Total Functional Capacity (TFC) =3 (i.e. Shoulson & Fahn Scale stages 1-3 inclusive) (7) 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. (8) Able to swallow study medication. (9) Able to perform Q-Motor tests. (10) 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: (1) Juvenile forms of HD. (2) Any form of chorea other than HD. (3) History of seizure, epilepsy or other convulsive disorder. (4) History of conditions susceptible to induce seizures such as severe traumatic brain injury, brain tumours, stroke. (5) History of neurosurgical procedure. (6) 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. (7) History of drug and/or alcohol abuse as per the DSM IV-TR criteria within 12 months prior to Baseline. (8) At imminent risk of self harm based on investigator’s clinical judgment, with a “yes” answer on item 4 or 5 on the CSSRS questionnaire. (9) Mini Mental State Exam (MMSE) total score = 23. (10) Used any investigational drugs within 30 days prior to Screening or 5 half lives, whichever is the longest. (11) Known allergy/sensitivity to the study drugs or their excipients. (12) A severe or ongoing unstable medical condition (e.g. cardiac, hepatic, renal, metabolic or endocrine). (13) Any clinically significant condition which, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial. (14) 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. (15) 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). (16) An estimated Creatinine Clearance (CrCl) of 3x ULN (18) Known history of hepatitis B or C or Human Immunodeficiency Virus (HIV) or positive serology at Screening. (19) Corrected QT interval using Bazett's correction (QTcB) >450 ms or other clinically significant ECG findings. (20) Receiving tetrabenazine within 4 weeks prior to Baseline (21) Receiving drugs at doses known to induce seizures with an incidence of more than 1% as per the reference list (22) Taking the following prohibited medications/substances: Strong Cytochrome (CYP) 3A4 inhibitors, strong CYP3A4 inducers and CYP2B6 substrates (Wash out prior to Baseline 30 days or 5 half lives,whichever is the longest). CYP1A2 substrates, CYP3A4 substrates and CYP2C19 substrates may be allowed and will be assessed on a case by case basis according to the dose received.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of BN82451B versus placebo after oral administration twice daily (bid) for 28 days in subjects with Huntington’s Disease (HD).;Secondary Objective: • To characterise the pharmacokinetics (PK) of BN82451B and its metabolites (BN2468 and BN7167) in subjects with HD. • To evaluate the effect of BN82451B compared with placebo, on quantitative measures of motor function (Q-Motor).;Primary end point(s): • Treatment emergent adverse events (TEAEs) • Physical examination • Neurological examination • Vital signs (heart rate, systolic and diastolic blood pressure) • 12-lead ECG • CSSRS • Biochemistry, haematology and urinalysis • Platelet function;Timepoint(s) of evaluation of this end point: • Treatment emergent adverse events (TEAEs) • Physical examination at Screening, Day -2, and EOS/early withdrawal • Neurological examination at Screening and Days -2, 7, 14, 21, 28, 30 and EOS/early withdrawal • Vital signs (heart rate, systolic and diastolic blood pressure) at Screening and Days -2, 1, 3, 7, 14, 21, 28, 30 and EOS/early withdrawal • 12-lead ECG at Screening and Days -2, 1, 3, 7, 14, 21, 28, 30 and EOS/early withdrawal • CSSRS at Screening and Days -2, 7, 14, 21, 28 and EOS/early withdrawal • Biochemistry, haematology and urinalysis at Screening and on Days -1, 7, 13, 21, 28 and 30 and EOS/early withdrawal • Platelet function at Days -2, 13, 28 and EOS/early withdrawal | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Full PK assessments -Q Motor test: • Choreomotography (position index and orientation index of grasp lift task) • Manumotography (grip force variability of grasp lift task) • Digitomotography (tap variability in index finger speeded tapping task) • Dysdiadochomotography (tap variability in alternating pronation/supination hand tapping task) • Pedomotography (tap variability in foot speeded tapping task);Timepoint(s) of evaluation of this end point: Pharmacokinetic Evaluations: • Full PK assessments will be performed on Days 1, 14 and 28 after the morning dose. • After the morning dose on Days 7 and 21, 3 blood samples will be collected up to 12 hours post dose. • Pre morning dose concentration will be performed on Days 12, 13, 26 and 27. • Twelve hour urinalysis for PK assessments will be carried out on Days 1, 13 and 27. Q-Motor tests will be assessed at Screening (training), Day -2, -1, 1, 4, 7, 10, 13, 14, 17, 20, 21, 24, 27, 28, 30 and EOS/early withdrawal. | — |
Countries
Germany
Contacts
Public ContactExecutive VP Research & Development
Ipsen Pharma
Outcome results
None listed