To determine the safety and efficacy of Dimebon in patients with mild to moderate Huntington Disease
ID
Source
Brief title
Condition
- Neurological disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective:
• To evaluate the long-term safety of dimebon (latrepirdine) in Huntington
disease (HD) subjects who have successfully completed 26 weeks of blinded
treatment in the HORIZON protocol (DIM20).
Secondary outcome
• To observe the long-term functional and motor symptoms of HD during
open-label treatment with dimebon, using the Unified Huntington Disease Rating
Scale (UHDRS) Total Functional Capacity (TFC) and Total Motor scores
Background summary
The purpose of this study to evaluate the long-term safety of dimebon
(latrepirdine) at a dose of 60mg per day. The study will also evaluate other HD
symptoms and overall functioning in people with HD. Motor function will also be
assessed, but it is not expected that dimebon will improve any movement
disorder. The length of time of the open-label extension will be different for
each participant, depending on when they enroll in the HORIZON study and begin
HORIZON-Plus. The study will continue and patients will have access to the
study drug until the regulatory authority in the Netherlands approves the drug
and it is available for the doctor to prescribe, or until it is found that the
study drug is not safe or effective. Patients may stay on the study drug
throughout the study or may stop earlier if they or their physician believes it
is in their best interest.
HORIZON-Plus is being conducted at about 50 Huntington Study Group (HSG) and
European Huntington*s Disease Network (EHDN) research centers in North America,
Europe and Australia, and will enroll about 350 subjects.
Study objective
To determine the safety and efficacy of Dimebon in patients with mild to
moderate Huntington Disease
Study design
This study is an open-label extension study of oral dimebon (20 mg three times
per day [TID]), administered to subjects with HD who have successfully
completed 26 weeks of blinded treatment in the HORIZON study (DIM20). Up to
approximately 350 subjects (the randomization cohort anticipated for HORIZON)
will be offered participation in this extension study. All subjects will
receive dimebon 10 mg TID for the first seven days of therapy, before
escalating to dimebon 20 mg TID until marketing authorization in their
respective countries, or until study termination at the discretion of the
Sponsor (for reasons including lack of efficacy noted after full analysis of
the HORIZON study) or if recommended by the HORIZON Data Monitoring Committee
(DMC). Subjects, Site Investigators, and the members of the Sponsor*s staff
overseeing the conduct of the study will remain blinded to the original
treatment assignment in the HORIZON study upon enrollment into HORIZON-Plus.
Throughout the study, safety and tolerability will be assessed by recording of
adverse events, monitoring of vital signs and physical examinations, safety
laboratory evaluations, and 12-lead electrocardiograms (ECG). In addition, the
Columbia Suicide Severity Rating Scale will be administered at each study visit
to collect and record suicidal ideation and attempts in a standardized fashion.
Central laboratories will be utilized for laboratory safety assessments and ECG
assessments. The last assessment of data prior to initiation of dimebon will
serve as the baseline reference for subsequent HORIZON-Plus assessments for
safety analyses. For subjects randomized to placebo in the HORIZON study this
will be the HORIZON Week 26 visit. For subjects randomized to dimebon in the
HORIZON study and continuing to receive dimebon this will be the HORIZON
Baseline visit.
HD progression will be evaluated through serial motor and functional
evaluations using the UHDRS Total Motor and UHDRS TFC assessments. The last
assessment of data prior to initiation of study drug in HORIZON will serve as
the baseline reference for assessing change in HD progression measures.
Intervention
Patient will be treated with oral Dimebon
Study burden and risks
The safety, tolerability, and effectiveness of Dimebon in HD are being
investigated in this study. Patient may experience side effects from taking the
study drug. The study drug may cause all, some or none of the following side
effects. Dimebon has occasionally been associated with a sedative (a state of
calm, restfulness, or drowsiness) effect, dry mouth, constipation, depressed
mood, headache, nausea and difficulty sleeping. In addition, there is always
the risk of unknown side effects occurring.
There is no guarantee of any direct benefit as a result of participating in
this research study. It is possible that the study drug may be effective in
reducing your symptoms of HD, but this cannot be guaranteed. It may have no
effect or even worsen your HD symptoms.
201 Spear Street, Third Floor
San Fransisco
US
201 Spear Street, Third Floor
San Fransisco
US
Listed location countries
Age
Inclusion criteria
Subjects eligible to participate in this study are persons who:
1. Have successfully completed 26 weeks of blinded treatment in the HORIZON study and completed Week 26 assessments;
2. Are willing and able to give informed consent. If the subject is not competent, a mentally competent legally-acceptable representative must provide informed consent on their behalf, and the subject should provide assent;
3. Have a caregiver who assists the subject, can oversee study drug administration, and provide written informed consent;
4. If female, are either a) of childbearing potential and compliant in using adequate birth control or b) not of childbearing potential. Adequate birth control is defined as consistent practice of an effective and accepted method of contraception (hormone-based, intrauterine device, barrier contraception [e.g., condom or occlusive cap {diaphragm or cervical/vault caps} with spermicidal foam/gel/film/cream/suppository], vasectomized partner, or sexual abstinence) throughout the duration of the study. Women not of childbearing potential may have undergone menopause or permanent sterilization (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation). Menopause is defined as one year without menses. If the subject*s menopausal status is in question, a follicle-stimulating hormone (FSH) level of > 40 milli-international units per milliliter (mIU/mL) must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented;
5. If male, is either a) of reproductive potential and compliant in using adequate birth control through 30 days after the last dose of study drug or b) not of reproductive potential. Surgical sterilization must be documented. Adequate birth control for males is defined as a condom and spermicidal gel or foam, or abstinence throughout the duration of the study;
6. Capable of complying with study procedures, including being able to swallow tablets the size of the study drug.
Exclusion criteria
Subjects ineligible to participate in this study are persons who:
1. Have any major medical illness or unstable medical condition that may interfere with their ability to comply with study procedures and abide by study restrictions, or may interfere with the ability to interpret safety information;
2. Are pregnant or lactating females;
3. Plan to use bupropion, clozapine, or non-selective antihistamines such as chlorpheniramine and diphenhydramine during this extension study;
4. Plan to participate in another study of an investigational agent for HD;
5. Have a Columbia Suicide Severity Rating Scale response of *Yes* to question four (4) or five (5) of the Suicidal Ideation category during the Week 26 visit for HORIZON;
6. Have any condition or reason that, in the opinion of the investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-018123-32-NL |
| CCMO | NL32109.058.10 |