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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT00665223
First received: April 22, 2008
Last updated: March 28, 2013
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
Huntington's Disease
Drug: ACR16
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre, Multinational, Randomized, Double-blind, Parallel-group Study Comparing ACR16 Versus Placebo for the Symptomatic Treatment of Huntington's Disease

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability assessed from adverse event profile. [ Time Frame: After 1, 4, 5, 8, 12, 26 and 30 weeks ] [ Designated as 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 ] [ Designated as safety issue: No ]

Enrollment: 437
Study Start Date: April 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACR16 - once daily dose
Participant received ACR16 45 mg once daily for four weeks. Weeks 5-26, ACR16 45 mg capsule and one placebo capsule were taken as two separate doses.
Drug: ACR16
45 mg capsules Capsules will be swallowed whole with water. For the first four weeks, one capsule should be taken early in the morning before food. After four weeks, one capsule should be taken early in the morning before food and one in the early afternoon at least 1 hour after food.
Drug: Placebo
Placebo capsules. Capsules will be swallowed whole with water. For the first four weeks, one capsule should be taken early in the morning before food. After four weeks, one capsule should be taken early in the morning before food and one in the early afternoon at least 1 hour after food.
Experimental: ACR16 - twice daily dose
Participant received ACR16 45 mg once daily for four weeks. Weeks 5-26, an ACR16 45 mg capsule was taken twice daily as two separate doses (total dose: 90 mg).
Drug: ACR16
45 mg capsules Capsules will be swallowed whole with water. For the first four weeks, one capsule should be taken early in the morning before food. After four weeks, one capsule should be taken early in the morning before food and one in the early afternoon at least 1 hour after food.
Placebo Comparator: Placebo
Participant received a placebo capsule once daily for four weeks. Weeks 5-26, a placebo capsule was taken twice daily as two separate doses.
Drug: Placebo
Placebo capsules. Capsules will be swallowed whole with water. For the first four weeks, one capsule should be taken early in the morning before food. After four weeks, one capsule should be taken early in the morning before food and one in the early afternoon at least 1 hour after food.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00665223

Locations
Austria
LKH -Univ. Klinikum Graz, Universitaetsklinik fur Psychiatrie Graz
Graz, Styria, Austria, 8036
Innsbruck Medical University, Anichstraße 35
Innsbruck, Tyrol, Austria, A-6020
Belgium
University Hospital Gasthuisberg
Leuven, Flemish Brabant, Belgium, 3000
France
Hôpital Purpan, Place Docteur-Baylac, Bâtiment F
Toulouse Cedex 9, Midi-Pyrénées region, France, 31059
CHU Roger Salengro
Lille Cedex, Nord-Pas de Calais, France, 59037
Hôpital Nord, CHU d'Amiens, Service de Neurologie
Amiens Cedex 1, Picardie, France, 80054
CHU La Timone, 264 Rue Saint Pierre
Marseille Cedex 05, Provence-Alpes-Cote d'Azur, France, 13385
Germany
Universitätsklinik Ulm, Neurologie/ Oberer Eselberg 45/1
Ulm, Baden-Württemberg, Germany, 89081
Klinikum rechts der Isar der Technischen Universität München, Neurologische Klinik und Poliklinik, Ismaninger Str. 22
München, Bavaria, Germany, 81675
Isar Amper Klinikum gemeinnützige GmbH, Klinik Taufkirchen (Vils), Bräuhausstr.5
Taufkirchen (Vils), Bavaria, Germany, 84416
St. Josef Hospital, Ruhr University Bochum, Gudrunstraße 56
Bochum, North Rhine-Westphalia, Germany, 44791
Westfaelische Wilhelms-Universitaet Muenster, Klinik fur Neurologie
Muenster, North Rhine-Westphalia, Germany, 48149
Universitat Dresden, Klinikum Carl Gustav Carus, Fetscherstr. 74
Dresden, Saxony, Germany, 01307
Klinik für Psychiatrie und Psychotherapie, Charité - Universitätsmedizin Berlin, Schumannstrasse 20/21
Berlin, Germany, 10117
Italy
Fondazione IRCCS Istituto Nazionale Neurologico "Carlos Besta", Department of Movement Disorders, 11 via Celoria
Milano, Lombardy, Italy, 20133
IRCCS Neuromed, Localita Camarelle
Pozzilli, Molise, Italy, 86077
Portugal
University Hospital of Coimbra, Av. Rissaya Barreto
Coimbra, Baixo Mondego, Portugal, 3000-075
Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz
Lisboa, Portugal, 1649-028
Spain
Hospital Mútua de Terrassa, C/ Castell
Terrassa, Catalonia, Spain, 08225
Hospital Clinic of Barcelona, Calle Villarroel, 170
Barcelona, Spain, 08036
Hospital Ramon y Cajal, Carretera Colemenar km 9.100
Madrid, Spain, 28034
Hospital Universitario La Fe, Avda. Campanar 21,
Valencia, Spain, 46009
United Kingdom
R&D Headquarters, Barberry Centre, 25 Vincent Drive
Birmingham, England/West Midlands, United Kingdom, B15 2SG
Department of Clinical Genetics, St Mary's Hospital, Hathersage Road
Manchester, North West England, United Kingdom, M13 9WL
First Floor Argyll House, Fosterhill, Cornhill Road
Aberdeen, Scotland, United Kingdom, AB25 2ZR
SE Scotland Genetic Service, Western General Hospital, Crewe Road
Edinburgh, Scotland, United Kingdom, EH4 2XU
Churchill Hospital, Old Road, Headington
Oxford, South East England, United Kingdom, OX3 7LJ
Academic Neurology Unit, E Floor Medical School Beech Hill Road
Sheffield, South Yorkshire, United Kingdom, S10 2RX
Institute of Human Genetics, Centre for Life, Central Parkway
Newcastle on Tyne, Tyne and Wear, United Kingdom, NE1 3BZ
Cardiff University School of Medicine, Department of Neurology & Medical Genetics, Heath Park
Cardiff, Wales, United Kingdom, CF14 4XN
Cambridge Centre for Brain repair, Cambridge University
Cambridge, United Kingdom, CB2 2PY
Sponsors and Collaborators
Teva Pharmaceutical Industries
  More Information

No publications provided by Teva Pharmaceutical Industries

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT00665223     History of Changes
Other Study ID Numbers: ACR16 C008
Study First Received: April 22, 2008
Last Updated: March 28, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicinal Products and Health Products
Austria: Agency for Health and Food Safety
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines
Italy: The Italian Medicines Agency

Keywords provided by Teva Pharmaceutical Industries:
Huntington's Disease

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Chorea
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Dyskinesias
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mental Disorders
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on October 20, 2014