Clinical trial NCT02231580: Study Exploring Safety, Pharmacokinetic and Pharmacodynamic of BN82451 in Male Huntington's Disease Patients
Official title: A Dose Escalation, Proof of Concept, Phase IIa Study to Investigate the Safety and Tolerability, the Pharmacokinetic and the Pharmacodynamic of BN82451B, Administered Twice Daily Over 4 Weeks, in Male Patients With Huntington's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Huntington's Disease
Keywords: Neurodegenerative genetic disorder
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2014-09-04
Enrollment: 17
Sex: MALE
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Primary outcomes:
measure: Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs).
timeFrame: From Day 1 to end of study (a period of up to 7 weeks).
Secondary outcomes:
measure: Area Under the Plasma Concentration Time Curve (AUC)
timeFrame: 0-12 hours on Days 1, 14 and 28
measure: Peak Plasma Concentration (Cmax)
timeFrame: Days 1, 14 and 28
measure: Time to Peak Plasma Concentration (Tmax)
timeFrame: Days 1, 14 and 28
measure: Change From Baseline to Day 28 in the Position-index as Determined by Choreomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Orientation-index as Determined by Choreomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Grip Force Variability as Determined by Manumotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Isometric Grip Forces as Determined by Manumotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Onset Intervals (IOI) as Assessed by Digitomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of Tap Durations (TD) as Assessed by Digitomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Peak Intervals (IPI) as Assessed by Digitomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Tap Intervals (ITI) as Assessed by Digitomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Variability of Peak Tapping Forces (TF) as Assessed by Digitomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Tapping Frequency (Freq) as Assessed by Digitomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Dysdiadochomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Dysdiadochomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Dysdiadochomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Dysdiadochomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Dysdiadochomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Dysdiadochomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Pedomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Pedomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Pedomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Pedomotography
timeFrame: Baseline (Day-1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Pedomotography
timeFrame: Baseline (Day -1) to Day 28
measure: Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Pedomotography
timeFrame: Baseline (Day -1) to Day 28
Other outcomes:
Locations:
city: Monchengladbach
country: Germany
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: