A Study of Treatment With ACR16 in Patients With Huntington's Disease

Official Title: “A Multicentre, Multinational, Randomized, Double-blind, Parallel-group Study Comparing ACR16 Versus Placebo for the Symptomatic Treatment of Huntington's Disease”

The purpose of this study is to determine if ACR16 is effective and safe in the symptomatic treatment of Huntington's disease.

The primary objective in the present study is to confirm whether ACR16 is efficacious in improving voluntary motor function in Huntington's disease, symptoms that seem to be most important for the functional disability associated with the disorder. To achieve this, patients are randomised to ACR16 45mg qd, ACR16 45mg bd, or placebo treatment in equal proportions in a parallel design for treatment duration of 26 weeks.

Intervention(s) in this Clinical Trial

• Drug: ACR16
  • First four weeks - ACR16 45mg qd - one active 45mg capsule daily After four weeks - ACR16 45mg qd - one active 45mg capsule and one placebo capsule taken as two separate doses.
• Drug: ACR16
  • First four weeks - ACR16 45mg qd - one active 45mg capsule daily After four weeks - ACR16 45mg bd - two active 45mg capsules taken as two separate doses.
• Drug: Placebo
  • First four weeks - ACR16 Placebo - one placebo capsule daily After four weeks - ACR16 Placebo - two placebo capsules taken as two separate doses.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Placebo Comparator: 3

Primary Measures

• The primary objective is to assess the effects of ACR16 on voluntary motor function in HD patients, as defined as the sum score of items 4-10 and 13-15 of the UHDRS motor assessment (a modified motor score mMS) at 26 weeks of treatment.
  • Time Frame: last timepoint at which outcome is assessed is after 26 weeks
    Safety Issue?: No

Secondary Measures

• Safety and tolerability assessed from adverse event profile.
  • Time Frame: After 1, 4, 5, 8, 12, 26 and 30 weeks
    Safety Issue?: Yes
• The effects of ACR16 on CGI, cognitive function, behaviour and symptoms of depression and anxiety.
  • Time Frame: At 4, 8, 12 and 26 weeks
    Safety Issue?: No

Inclusion Criteria:

• Able to provide written Informed Consent prior to any study related procedure.
• Huntington's disease diagnosed with the aid of clinical features and a positive family history and/or the presence of ≥ 36 CAG repeats in the Huntington gene.
• Male or female age ≥ 30 years.
• Willing and able to take oral medication and able to comply with the study specific procedures.
• Ambulatory, being able to travel to the assessment centre, and judged by the Investigator as likely to be able to continue to travel for the duration of the study.
• Availability of a caregiver or family member to accompany the patient.
• A sum of ≥ 10 points on the mMS at the screening visit.
• For patients taking allowed antipsychotic medication, the dosing of medication must have been kept constant for at least 6 weeks before randomisation. The allowed antipsychotic medication is Amisulpride, Haloperidol, Olanzapine, Risperidone, Sulpiride, or Tiapride.
• For patients taking allowed antidepressant or other psychotropic medication, the dosing of medication must have been kept constant for at least 6 weeks before randomisation.
• Willing to provide a blood sample for CAG analysis (where CAG result is not already available).
• In France only, the patient must be affiliated to a social security system or be a beneficiary of such a system.

Exclusion Criteria:

• Unable to give written informed consent.
• Treatment with any non-allowed antipsychotic medication within 12 weeks of randomisation. The non-allowed antipsychotic medication is any medication other than
• Amisulpride, Haloperidol, Olanzapine, Risperidone, Sulpiride, or Tiapride.
• Treatment with the antidepressants Fluoxetine or Paroxetine within 6 weeks of randomisation.
• Use of Tetrabenazine within 12 weeks of randomisation, or at any time during the study period.
• Treatment with any investigational product within 4 weeks of randomisation.
• Use of tricyclic antidepressants, class I antiarrhythmics, and strong CYP2D6 inhibitors such as Ajmalicine, Chinidin/Quinidine and Ritonavir, within 6 weeks of randomisation.
• Patients previously included into this study.
• A prolonged QTc interval at screen (defined as a QTc interval of > 450 msec for males or > 470 msec for females), or other clinically significant heart conditions.
• Creatinine clearance <40mL/min as measured at the screening visit.
• Any clinically significant, abnormal, baseline laboratory result which in the opinion of the Investigator, affects the patients' suitability for the study or puts the patient at risk if he/she enters the study.
• Clinically significant hepatic or renal impairment.
• Patients with a history of epilepsy or a history of seizure(s) of unknown cause.
• Severe intercurrent illness, which, in the opinion of the Investigator, may put the patient at risk when participating in the trial or may influence the results of the trial or affect the patients' ability to take part in the trial.
• Alcohol and/or drug abuse as defined by DSM IV-TR criteria for substance abuse - this includes the illicit use of cannabis within the last 12 months.
• Patients with suicidal ideation, defined as a positive score on criteria for major depressive episode, item A9 on the DSM-IV-TR criteria for a Major Depressive Episode.
• Females who are pregnant or lactating.
• Females who are of child bearing potential and not taking adequate contraceptive precautions are excluded from the trial. Females of child bearing potential taking acceptable contraceptive precautions can be included.
• Known allergy to any ingredients of the trial medication or placebo.
• Any previous participation in a clinical study with ACR16.
• Patients currently receiving deep brain stimulation.
• Patients with a history of surgical procedures aiming to improve the symptoms of Huntington's disease, such as neural transplantations, lesions of the central nervous system, infusions of neurotrophic agents or previous attempts of deep brain stimulation.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: NeuroSearch A/S Industry

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00665223

Study ID Number: ACR16 C008

ClinicalTrials.gov Identifier: NCT00665223

Health Authority: Germany: Federal Institute for Drugs and Medical Devices