A Study of Treatment With Pridopidine (ACR16) in Participants With Huntington's Disease

Huntington's Disease Clinical Trial

— MermaiHD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00665223
• Other study ID #: ACR16 C008
• Status: Completed
• Phase: Phase 3
• Start date: April 24, 2008
• Est. completion date: June 14, 2010

Study information

• Verified date: July 2023
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: June 14, 2010
• Est. primary completion date: June 14, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• ACR16
Capsules will be swallowed whole with water.
• Placebo
Capsules will be swallowed whole with water.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Italy,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The mMS is a subscale of the UHDRS total motor score and comprises 13 responses from the 10 items, 4-10 and 13-15, from the UHDRS motor assessment. The items for mMS include dysarthria, tongue protrusion, finger taps (right and left), pronate/supinate hands (right and left), luria - first-hand-palm sequencing, arms rigidity (right and left), body bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these items are rated on a scale of 0 (normal) to 4 (marked impairment). Total score ranges from 0 to 52, with higher scores indicating more severe motor impairment.	Baseline, Week 26
Secondary	The UHDRS Functional Assessment at Week 26	The UHDRS Functional Assessment considers 25 items associated with functional problems. The participant scores 1 point for every item to which they respond positively (zero points for negative responses). Total score ranges from 0 (worst) to 25 (best). Higher scores indicate better functional ability.	Week 26
Secondary	Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score	Global improvement is rated by the investigator on a 7-point scale as: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse.	Week 26
Secondary	Change From Baseline in Stroop Word Reading Test at Week 26	The Stroop test measures the ability to concentrate and ward off distractions. The test consists of three items: (i) colour naming; (ii) word reading; (iii) interference. The word reading test requires participants to read colour words written in black and each response is scored as the number of correct answers made in 45 seconds. Higher scores indicate less severe disease, and an increase in score represents an improvement.	Baseline, Week 26
Secondary	Change From Baseline in Total UHDRS Behavioral Assessment Score at Week 26	The total behavioral assessment score is the sum of the 11 products (depressed mood, apathy, low self-esteem/guilt, compulsive behavior, anxiety, irritable behavior, perseverative/obsessive thinking, disruptive/aggressive behavior, suicidal thoughts, delusions, and hallucinations) of frequency and severity symptom scores and excluded the 3 yes/no questions relating to confusion, dementia, and depression. Frequency is rated on a scale of 0 (never or almost never) to 4 (very frequently, most of the time). Severity is rated on a scale of 0 (no evidence) to 4 (severe). Total behavior score ranges from 0 (no impairment) to 88 (severe impairment), with higher scores indicating greater behavioral impairments.	Baseline, Week 26
Secondary	Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 26	HADS is a self-administered instrument reliable for detecting states of depression and anxiety. It includes 2 subscales: Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (HADS-D) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale is comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score ranges from 0 to 21 for each subscale where higher scores indicate greater severity of anxiety and depression symptoms. The total HADS score was a composite score summed of all 14 items for a total range of 0 to 42. Lower change from baseline scores indicate improvement.	Baseline, Week 26
Secondary	Randomized Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any change from the participant's baseline (pre-treatment) condition, other than improvement, that did not necessarily have causal relationship with the study drug. TEAEs were defined as AEs that began after ACR16/placebo administration through week 26 or up to week 30 for participants not continuing in the open-label period. AEs included both serious adverse events (SAEs) and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.	Baseline up to Week 30
Secondary	Open-label Phase: Number of Participants With TEAEs	An AE was defined as any change from the participant's baseline (pre-treatment) condition, other than improvement, that did not necessarily have causal relationship with the study drug. TEAEs were defined as adverse events that began after ACR16/placebo administration through Week 56. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.	Week 26 up to Week 56