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

Huntington Disease Clinical Trial

— HART  

Official title:

A Multi-center, North American, Randomized, Double-blind, Parallel Group Study Comparing Three Doses of ACR16 Versus Placebo for the Symptomatic Treatment of Huntington Disease (HART)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00724048
• Other study ID #: ACR16 C009
• Status: Completed
• Phase: Phase 2
• Start date: October 24, 2008
• Est. completion date: July 26, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 227
• Est. completion date: July 26, 2010
• Est. primary completion date: July 26, 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, including consent to genotyping of the CYP2D6 gene.

• Clinical features of HD, 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 to comply with the study specific procedures.

• Ambulatory, being able to travel to the assessment center, 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 to two visits.

• A sum of = 10 points on the mMS at the screening visit.

• For participants taking allowed antidepressants or other psychotropic medication , the dosing of medication must have been kept constant for at least 6 weeks before baseline visit.

Exclusion Criteria:

• Treatment with any antipsychotic medication (neuroleptics) within 8 weeks of baseline visit, or at any time point during the study period.

• Use of tetrabenazine within 12 weeks of baseline visit, or at any time during the study period.

• Treatment with any investigational product within 4 weeks of baseline visit.

• Use of tricyclic antidepressants or class I antiarrhythmics within 6 weeks of baseline visit, or at any time during the study period.

• Use of concomitant medication that may lower the seizure threshold within 6 weeks of baseline visit, or at any time during the study period .

• Use of metoclopramide within 12 weeks of baseline visit, or at any time during the study period.

• Participants currently receiving deep brain stimulation (DBS).

• Participants with a history of surgical procedures aiming to improve the symptoms of Huntington disease, such as neural transplantations, lesions of the central nervous system, infusions of neurotrophic agents or previous attempts of deep brain stimulation.

• Participants previously randomized into this study.

• A prolonged QTc interval at Screening Visit (defined as a QTc interval of > 450 milliseconds [msec] for males or > 470 msec for females), or other clinically significant heart conditions as judged by the investigator.

• 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 participant' 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 known history of epilepsy or a history of febrile seizure(s) or 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 subjects' ability to take part in the trial.

• Alcohol and/or drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM IV-TR) criteria for Substance Abuse - this includes the illicit use of cannabis within the last 12 months prior to Screening Visit

• Participants with suicidal ideation as 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 or who intend to become pregnant during the study period.

• Females who are of child bearing potential and not taking adequate contraceptive precautions are excluded from the trial. (Females of childbearing 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.

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Drug:
• ACR16
ACR16 will be administered per dose and schedule specified in the arm description.

Other:
• Placebo
Placebo matching to ACR16 will be administered per schedule specified in the arm description.

Locations

Country	Name	City	State
Canada	University of Alberta Glenrose Rehab Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	The Centre for Addiction and Mental Health	Markham	Ontario
Canada	Hotel-Dieu Hospital-CHUM	Montreal	Quebec
Canada	Parkinsons and Neurodegenerative Disorders Clinic	Ottawa	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
United States	Albany Medical College	Albany	New York
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Charlestown	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Ohio State University Parkinson's Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Booth Gardner Parkinson's Care Center	Kirkland	Washington
United States	Colorado Neurological Institute	Littleton	Colorado
United States	North Shore-LIJ Health System	Manhasset	New York
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Struthers Parkinson's Center	Saint Louis Park	Minnesota
United States	University of California	San Diego	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Canada, 

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 UHDRS Motor Assessments) at Week 12	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 included 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 were rated on a scale of 0 (normal) to 4 (marked impairment). Total score ranged from 0 to 52, with higher scores indicating more severe motor impairment. The last observation carried forward (LOCF) method was used to generate an mMS score for each participant for Week 12 assessment.	Baseline, Week 12
Secondary	Change From Baseline in Total Motor Score (TMS)	The UHDRS Motor Assessment comprises 31 responses from the 15 items, where each response is rated on a 5-point scale from 0 (normal) to 4 (maximally abnormal). The Total Motor Score (TMS) is the sum of all the 31 responses with higher scores indicating more severe motor impairment than lower scores.	Basline, Week 12
Secondary	Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale	The CGI-C was 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 12
Secondary	Change From Baseline in Stroop Word Reading Test	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 12
Secondary	Change From Baseline in Total UHDRS Behavioral Assessment Score	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 12
Secondary	Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score	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 0-42. Lower change from baseline scores indicate improvement.	Baseline, Week 12
Secondary	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 adverse events that began after ACR16/placebo administration. 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'.	Baseline up to Week 14