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

Ipsen0 sites17 target enrollmentSeptember 1, 2014

ConditionsHuntington's Disease

InterventionsBN82451B Placebo

DrugsBN82451B Placebo

Overview

Phase: Phase 2
Intervention: BN82451B
Conditions: Huntington's Disease
Sponsor: Ipsen
Enrollment: 17
Primary Endpoint: Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs).
Status: Terminated
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

September 1, 2014

End Date

March 31, 2016

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

Ipsen

Responsible Party

Sponsor

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
•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
•Used any investigational drugs within 30 days prior to Screening or 5 half lives, whichever is the longest.

Arms & Interventions

BN82451B

BN82451B capsule: Up to 3 dose levels (40, 60 or 80 mg) twice daily administered orally.

Intervention: BN82451B

Placebo

Placebo capsule: Up to 3 dose levels (40, 60 or 80 mg) twice daily administered orally.

Intervention: Placebo

Outcomes

Primary Outcomes

Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs).

Time Frame: From Day 1 to end of study (a period of up to 7 weeks).

The safety and tolerability of BN82451B versus placebo was determined after oral administration b.i.d. for 28 days in patients with HD. Numbers of patients experiencing TEAEs, including information on seriousness, intensity, drug relationship and those leading to withdrawal are presented for all doses of BN82451B and placebo.

Secondary Outcomes

Area Under the Plasma Concentration Time Curve (AUC)(0-12 hours on Days 1, 14 and 28)
Change From Baseline to Day 28 in the Position-index as Determined by Choreomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Orientation-index as Determined by Choreomotography(Baseline (Day -1) to Day 28)
Peak Plasma Concentration (Cmax)(Days 1, 14 and 28)
Time to Peak Plasma Concentration (Tmax)(Days 1, 14 and 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Pedomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Pedomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Grip Force Variability as Determined by Manumotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Isometric Grip Forces as Determined by Manumotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Onset Intervals (IOI) as Assessed by Digitomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of Tap Durations (TD) as Assessed by Digitomotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Peak Intervals (IPI) as Assessed by Digitomotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Tap Intervals (ITI) as Assessed by Digitomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Variability of Peak Tapping Forces (TF) as Assessed by Digitomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Dysdiadochomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Dysdiadochomotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Dysdiadochomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Pedomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Tapping Frequency (Freq) as Assessed by Digitomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Dysdiadochomotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Dysdiadochomotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Dysdiadochomotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Pedomotography(Baseline (Day-1) to Day 28)
Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Pedomotography(Baseline (Day -1) to Day 28)
Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Pedomotography(Baseline (Day -1) to Day 28)