Huntington DiseasePhase 2HARTNCT00724048
A Study of Pridopidine (ACR16) for the Treatment of Participants With Huntington's Disease
A Phase 2 study testing ACR16 in people with Huntington Disease, run by Teva Branded Pharmaceutical Products R&D, Inc. at 28 sites in 2 countries.
Trial summary
The purpose of this study is to determine if ACR16 is effective and safe in the symptomatic treatment of Huntington's Disease. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Huntington Disease
- What is being tested?
- ACR16
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 227 participants
- Where
- 28 sitesin 2 countries
- Study dates
- 24 Oct 2008to 26 Jul 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
28 sites in 2 countries.
28 sites in 2 countries
United States22 sites
Albany Medical College
Albany, New York, 12208
University of Maryland School of Medicine
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21287-7281
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Massachusetts General Hospital
Charlestown, Massachusetts, 02129
Rush University Medical Center
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45219
Ohio State University Parkinson's Center
Columbus, Ohio, 43210
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-9036
Baylor College of Medicine
Houston, Texas, 77030
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Booth Gardner Parkinson's Care Center
Kirkland, Washington, 98034
Colorado Neurological Institute
Littleton, Colorado, 80120
North Shore-LIJ Health System
Manhasset, New York, 11030
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
University of Pennsylvania
Philadelphia, Pennsylvania, 19107
University of Rochester
Rochester, New York, 14618
Struthers Parkinson's Center
Saint Louis Park, Minnesota, 55426
University of California
San Diego, California, 92161
Washington University School of Medicine
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33612
Canada6 sites
University of Alberta Glenrose Rehab Hospital
Edmonton, Alberta, T5G 0B7
London Health Sciences Centre
London, Ontario, N6A 5A5
The Centre for Addiction and Mental Health
Markham, Ontario, L6B1C9
Hotel-Dieu Hospital-CHUM
Montreal, Quebec, H2L4M1
Parkinsons and Neurodegenerative Disorders Clinic
Ottawa, Ontario, K1G4G3
University of British Columbia
Vancouver, British Columbia, V6T 2B5
About this study
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)
The purpose of this study is to determine if ACR16 is effective and safe in the symptomatic treatment of Huntington's Disease.
- Conditions
- Huntington Disease
- Being tested
- ACR16, Placebo
- Keywords
- Huntington Disease
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACR16Drug
Also called pridopidine
ACR16 will be administered per dose and schedule specified in the arm description.
PlaceboOther
Placebo matching to ACR16 will be administered per schedule specified in the arm description.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive a placebo capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), placebo capsule will be taken twice daily (BID) as 2 separate doses. Receives: Other: Placebo |
| ACR16 10 mg BID | Experimental | Participants will receive ACR16 10 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 10 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 20 mg). Receives: Drug: ACR16 |
| ACR16 22.5 mg BID | Experimental | Participants will receive ACR16 22.5 mg capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 22.5 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 45 mg). Receives: Drug: ACR16 |
| ACR16 45 mg BID | Experimental | Participants will receive ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 45 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 90 mg). Receives: Drug: ACR16 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 12
Secondary outcomes (6)
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.
Measured: Basline, Week 12
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.
Measured: Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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'.
Measured: Baseline up to Week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2008 (estimated)
- Study start24 Oct 2008
- Primary completion26 Jul 2010
- Study completion26 Jul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 227 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Teva Medical Expert, Study director, Teva Branded Pharmaceutical Products R&D, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00724048
- Sponsor's protocol ID
- ACR16 C009
- Acronym
- HART
- Status last verified
- Jul 2023
- First submitted
- 24 Jul 2008
- Last updated
- 31 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Darpo B, Geva M, Ferber G, Goldberg YP, Cruz-Herranz A, Mehra M, Kovacs R, Hayden MR. Pridopidine Does Not Significantly Prolong the QTc Interval at the Clinically Relevant Therapeutic Dose. Neurol Ther. 2023 Apr;12(2):597-617. doi: 10.1007/s40120-023-00449-w. Epub 2023 Feb 22.
PubMed 36811812
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00724048
- Acronym / sponsor ID
- HART / ACR16 C009
- Conditions
- Huntington Disease
- Keywords
- Huntington Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 227 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Oct 2008 (actual)
- Primary completion
- 26 Jul 2010 (actual)
- Study completion
- 26 Jul 2010 (actual)
- First posted
- 29 Jul 2008 (estimated)
- Results
- Posted 31 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if ACR16 is effective and safe in the symptomatic treatment of Huntington's Disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboParticipants will receive a placebo capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), placebo capsule will be taken twice daily (BID) as 2 separate doses. |
| ACR16 10 mg BID | Experimental | Drug: ACR16Participants will receive ACR16 10 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 10 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 20 mg). |
| ACR16 22.5 mg BID | Experimental | Drug: ACR16Participants will receive ACR16 22.5 mg capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 22.5 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 45 mg). |
| ACR16 45 mg BID | Experimental | Drug: ACR16Participants will receive ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 45 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 90 mg). |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (21 listed)
- 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 .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACR16Also: pridopidineACR16 will be administered per dose and schedule specified in the arm description. | Drug | ACR16 10 mg BID, ACR16 22.5 mg BID, ACR16 45 mg BID |
| PlaceboPlacebo matching to ACR16 will be administered per schedule specified in the arm description. | Other | Placebo |
Primary outcome
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
Time frame: Baseline, 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.
6 secondary outcomes
Change From Baseline in Total Motor Score (TMS)
Time frame: Basline, Week 12
Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale
Time frame: Week 12
Change From Baseline in Stroop Word Reading Test
Time frame: Baseline, Week 12
Change From Baseline in Total UHDRS Behavioral Assessment Score
Time frame: Baseline, Week 12
Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score
Time frame: Baseline, Week 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Baseline up to Week 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36811812Darpo B, Geva M, Ferber G, Goldberg YP, Cruz-Herranz A, Mehra M, Kovacs R, Hayden MR. Pridopidine Does Not Significantly Prolong the QTc Interval at the Clinically Relevant Therapeutic Dose. Neurol Ther. 2023 Apr;12(2):597-617. doi: 10.1007/s40120-023-00449-w. Epub 2023 Feb 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teva Medical Expert study director
Teva Branded Pharmaceutical Products R&D, Inc.
28 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACR16 in people with Huntington Disease, run by Teva Branded Pharmaceutical Products R&D, Inc. at 28 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline, Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00724048, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2023.