Clinical trial NCT00665223: A Study of Treatment With Pridopidine (ACR16) in Participants With Huntington's Disease
Official title: A Multicentre, Multinational, Randomised, Double-Blind, Parallel-Group Study Comparing ACR16 45 mg Once-Daily or Twice-Daily Versus Placebo for the Symptomatic Treatment of Huntington's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Huntington's Disease
Keywords: Huntington's Disease
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2008-04-23
Enrollment: 437
Sex: ALL
Minimum age (years): 30
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 determine if ACR16 is effective and safe in the symptomatic treatment of Huntington's disease.

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 based on the Unified Huntington"s Disease Rating Scale (UHDRS) subscale. These symptoms seem to be most important for the functional disability associated with the disorder. To achieve this, participants are randomized to ACR16 45 mg once daily, ACR16 45 mg twice daily, or placebo treatment in equal proportions in a parallel design for a treatment duration of 26 weeks.

Eligibility 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 participant.
* A sum of ≥ 10 points on the mMS at the screening visit.
* For participants taking allowed antipsychotic medication, the dosing of medication must have been kept constant for at least 6 weeks before randomization. The allowed antipsychotic medication is Amisulpride, Haloperidol, Olanzapine, Risperidone, Sulpiride, or Tiapride.
* For participants taking allowed antidepressant or other psychotropic medication, the dosing of medication must have been kept constant for at least 6 weeks before randomization.
* Willing to provide a blood sample for CAG analysis (where CAG result is not already available).
* In France only, the participant 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 randomization. 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 randomization.
* Use of Tetrabenazine within 12 weeks of randomization, or at any time during the study period.
* Treatment with any investigational product within 4 weeks of randomization.
* Use of tricyclic antidepressants, class I antiarrhythmics, and strong CYP2D6 inhibitors such as Ajmalicine, Chinidin/Quinidine and Ritonavir, within 6 weeks of randomization.
* Participants previously included into this study.
* A prolonged QTc interval at screen (defined as a QTc interval of \> 450 milliseconds \[msec\] for males or \> 470 msec for females), or other clinically significant heart conditions.
* Creatinine clearance \<40 milliliters (mL)/minute (min) as measured at the screening visit.
* Any clinically significant, abnormal, baseline laboratory result which in the opinion of the Investigator, affects the participants' suitability for the study or puts the participant at risk if he/she enters the study.
* Clinically significant hepatic or renal impairment.
* Participants 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 participant at risk when participating in the trial or may influence the results of the trial or affect the participants' ability to take part in the trial.
* Alcohol and/or drug abuse as defined by Diagnostic and Statistical Manual - Fourth Edition - Text Revision (DSM IV-TR) criteria for substance abuse - this includes the illicit use of cannabis within the last 12 months.
* Participants 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.
* Participants currently receiving deep brain stimulation.
* Participants 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.

Primary outcomes:
measure: Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the Unified Huntington's Disease Rating Scale [UHDRS] Motor Assessments) at Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: The UHDRS Functional Assessment at Week 26
timeFrame: Week 26
measure: Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score
timeFrame: Week 26
measure: Change From Baseline in Stroop Word Reading Test at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Total UHDRS Behavioral Assessment Score at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 26
timeFrame: Baseline, Week 26
measure: Randomized Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Week 30
measure: Open-label Phase: Number of Participants With TEAEs
timeFrame: Week 26 up to Week 56
Other outcomes:
Locations:
city: Graz
country: Austria
facility: LKH -Univ. Klinikum Graz, Universitaetsklinik fur Psychiatrie Graz
state: Styria
city: Innsbruck
country: Austria
facility: Innsbruck Medical University, Anichstraße 35
state: Tyrol
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
state: Flemish Brabant
city: Toulouse Cedex 9
country: France
facility: Hôpital Purpan, Place Docteur-Baylac, Bâtiment F
state: Midi-Pyrénées Region
city: Lille Cedex
country: France
facility: CHU Roger Salengro
state: Nord-Pas De Calais
city: Amiens Cedex 1
country: France
facility: Hôpital Nord, CHU d'Amiens, Service de Neurologie
state: Picardie
city: Marseille Cedex 05
country: France
facility: CHU La Timone, 264 Rue Saint Pierre
state: Provence-Alpes-Cote d'Azur
city: Ulm
country: Germany
facility: Universitätsklinik Ulm, Neurologie/ Oberer Eselberg 45/1
state: Baden-Württemberg
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München, Neurologische Klinik und Poliklinik, Ismaninger Str. 22
state: Bavaria
city: Taufkirchen (Vils)
country: Germany
facility: Isar Amper Klinikum gemeinnützige GmbH, Klinik Taufkirchen (Vils), Bräuhausstr.5
state: Bavaria
city: Bochum
country: Germany
facility: St. Josef Hospital, Ruhr University Bochum, Gudrunstraße 56
state: North Rhine-Westphalia
city: Muenster
country: Germany
facility: Westfaelische Wilhelms-Universitaet Muenster, Klinik fur Neurologie
state: North Rhine-Westphalia
city: Dresden
country: Germany
facility: Universitat Dresden, Klinikum Carl Gustav Carus, Fetscherstr. 74
state: Saxony
city: Berlin
country: Germany
facility: Klinik für Psychiatrie und Psychotherapie, Charité - Universitätsmedizin Berlin, Schumannstrasse 20/21
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Neurologico "Carlos Besta", Department of Movement Disorders, 11 via Celoria
state: Lombardy
city: Pozzilli
country: Italy
facility: IRCCS Neuromed, Localita Camarelle
state: Molise
city: Coimbra
country: Portugal
facility: University Hospital of Coimbra, Av. Rissaya Barreto
state: Baixo Mondego
city: Lisboa
country: Portugal
facility: Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz
city: Terrassa
country: Spain
facility: Hospital Mútua de Terrassa, C/ Castell
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona, Calle Villarroel, 170
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal, Carretera Colemenar km 9.100
city: Valencia
country: Spain
facility: Hospital Universitario La Fe, Avda. Campanar 21,
city: Birmingham
country: United Kingdom
facility: R&D Headquarters, Barberry Centre, 25 Vincent Drive
state: England/West Midlands
city: Manchester
country: United Kingdom
facility: Department of Clinical Genetics, St Mary's Hospital, Hathersage Road
state: North West England
city: Aberdeen
country: United Kingdom
facility: First Floor Argyll House, Fosterhill, Cornhill Road
state: Scotland
city: Edinburgh
country: United Kingdom
facility: SE Scotland Genetic Service, Western General Hospital, Crewe Road
state: Scotland
city: Oxford
country: United Kingdom
facility: Churchill Hospital, Old Road, Headington
state: South East England
city: Sheffield
country: United Kingdom
facility: Academic Neurology Unit, E Floor Medical School Beech Hill Road
state: South Yorkshire
city: Newcastle on Tyne
country: United Kingdom
facility: Institute of Human Genetics, Centre for Life, Central Parkway
state: Tyne And Wear
city: Cardiff
country: United Kingdom
facility: Cardiff University School of Medicine, Department of Neurology & Medical Genetics, Heath Park
state: Wales
city: Cambridge
country: United Kingdom
facility: Cambridge Centre for Brain repair, Cambridge University
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: de Yebenes JG, Landwehrmeyer B, Squitieri F, Reilmann R, Rosser A, Barker RA, Saft C, Magnet MK, Sword A, Rembratt A, Tedroff J; MermaiHD study investigators. Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011 Dec;10(12):1049-57. doi: 10.1016/S1474-4422(11)70233-2. Epub 2011 Nov 7.