Huntington Disease, Irritability
Conditions
Keywords
Irritability
Brief summary
The purpose of this study is to assess efficacy and safety of dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg) in patients with irritability due to Huntington's disease.
Interventions
DRUGDextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg)
DM/Q 20mg/10mg one capsule once daily for 1 week, followed by DM/Q 20mg /10 mg twice daily for subsequent 4 weeks, and finally DM/Q 20mg/10mg once daily for 7days.
DRUGPlacebo
Placebo once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Sponsors
Cures Within Reach
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Verified HD mutation carriers; * Irritable as diagnosed by the Irritability Scale with a score \> 14; * Stable concomitant medication (no change of medication during last 30 days prior to inclusion); * Written informed consent by prospective study participant before conduct of any trial-related procedure. Participant must be able to make an informed decision of whether or not to participate in the study.
Exclusion criteria
* Hypersensitivity to dextromethorphan (e.g., rash, hives), quinine, mefloquine, quinidine, or dextromethorphan/quinidine with a history of thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome induced by these drugs; * Pregnant or nursing women; * Active suicidality based on the answer yes in questions 4 and 5 of the Columbia-Suicide Severity Rating Scale (baseline version); * Woman of childbearing potential, not using highly effective methods of contraception such as oral, topical or injected contraception, IUD, contraceptive vaginal ring, or double barrier method such as diaphragm and condom with spermicide) or not surgically sterile (via hysterectomy, ovarectomy or bilateral tubal ligation) or not at least one year post-menopausal; * Male not using an acceptable barrier method for contraception; * Presence of any medically not controllable disease (e.g. uncontrolled arterial hypertension or diabetes mellitus); * Clinically significant renal (calculated creatinine clearance \< 30 ml/min) or hepatic dysfunction; * Patients with pre-existing hepatic disease; * Individuals with a history or complete heart block, QTc prolongation or tornadoes de pointes, or at high risk of complete AV block; * Family history of congenital QT prolongation; * History of unexplained syncope within the past year; * Use of drugs containing quinidine, quinine, or mefloquine; * Individuals currently taking strong CYP3A4 inhibitors or tetrabenazine; * Use of certain antidepressants--amitriptyline, clomipramine, desipramine, fluoxetine, paroxetine, sertraline, venlafaxine; * Use of certain heart rhythm medications--amiodarone, flecainide, procainamide, propafenone; * Use of certain medicines to treat psychiatric disorders--chlorpromazine, haloperidol, perphenazine, pimozide, quetiapine, risperidone, thioridazine. * Use of tamoxifen; * Presence or history of seizures or diagnosed epilepsy; * Severe cognitive disorders defined as a score \< 18 on the MOCA; * Clinically relevant abnormal findings in the ECG, the vitals, in the physical examination or laboratory values at screening that could interfere with the objectives of the study or the safety of the subject as judged by the investigator; * Participation in another investigative drug trial within 2 months; * Subjects who are unlikely to be compliant and attend scheduled clinic visits as required as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Irritability as Assessed by The Irritability Scale. | Baseline | The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability. |
| Irritability as Assessed by The Irritability Scale | 4 weeks | The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress. | Baseline | Caregiver distress associated with the symptom is rated on an anchored 0- to 5-point scale, which total sum ranges from 0 to 60. Higher scores indicate greater caregiver distress related to patient's neuropsychiatric symptoms. |
| Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s). - Irritability/Aggression Subscale | Baseline | The PBA-s is a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease. The PBA-s is an 11-item scale rating the frequency and severity of symptoms. The total score for irritability/aggression subscale ranges from 0 to 32, with higher scores indicating greater behavioral symptoms severity. |
| Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s) - Irritability/Aggression Subscale | 4 weeks | The PBA-s is a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease. The PBA-s is an 11-item scale rating the frequency and severity of symptoms. The total score for irritability/aggression subscale ranges from 0 to 32, with higher scores indicating greater behavioral symptoms severity. |
| Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS. | Baseline | The TMS comprises the motor section of the UHDRS, a 31-item subscale that comprehensively evaluates motor aspects of HD. The overall 31 items are each rated from grade 0 (not affected) to grade 4 (most severely affected), resulting in a range of 0-124 points. |
| Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC). | Baseline | The TMC comprises 7 of the 31 items in the TMS, which are related to chorea symptoms. The total TMC score ranges from 0 to 28, with higher scores indicating greater chorea severity. |
| Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC). | Baseline | The TFC lists five stages of Huntington's Disease and five levels of function in the domains of workplace, finances, domestic chores, activities of daily living and requirements for unskilled or skilled care. The total TFC score ranges from 0 to 13, with higher scores signifying better functioning. |
| Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS). | Baseline | The HADS is a self-report, 14-item scale (7 items relate to anxiety and 7 relate to depression) used to determine the levels of anxiety and depression that a person is experiencing. The total score ranges from 0 to 42 (21 per subscale), with higher scores signifying worse symptoms. |
| Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation | 4 weeks | The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses. The first part (Items 1-5) rates an individual's degree of suicidal ideation on a 0-5 scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent and behaviors. The C-SSRS outcomes are categories and have binary responses (yes/no). Suicidal ideation is considered when the patient responds a yes answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5) on the C-SSRS. The sum of the 5 intensity item scores create a total score (range 0 to 25) to represent the intensity rating (higher scores indicate more severe suicidal ideation). |
| Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior. | Baseline | The questions 6-10 of the C-SSRS are related to suicidal behavior, and the outcome is a simple yes/no response. Suicidal behavior occurs if the patient answers a yes at any time during treatment to any one of the five suicidal behavior questions (Categories 6-10) on the C-SSRS. |
| Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA). | Baseline | The MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains with a total possible score of 0 to 30 points; a score of 26 or above is considered normal for the general population. |
| Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Baseline | The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. |
| Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | 4 weeks | The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. |
| Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain. | Baseline | The UHDRS - cognitive function assessment a phonetic verbal fluency test, the Symbol Digit Modalities Test, and the Stroop Interference Test. These tests do not have a predefined score range, but higher scores indicate better cognitive performance. |
| Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation. | Baseline | The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses. The first part (Items 1-5) rates an individual's degree of suicidal ideation on a 0-5 scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent and behaviors. The C-SSRS outcomes are categories and have binary responses (yes/no). Suicidal ideation is considered when the patient responds a yes answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5) on the C-SSRS. The sum of the 5 intensity item scores create a total score (range 0 to 25) to represent the intensity rating (higher scores indicate more severe suicidal ideation). |
| Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score. | Baseline | The NPI-Q is a 12-domain informant-based interview that assesses neuropsychiatric symptoms over the previous month.The total NPI-Q severity score ranges from 0 to 36, with higher scores indicate greater symptoms severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg), Then Placebo Dextromethorphan/quinidine (DM/Q) 20mg/10mg one capsule once daily for 1 week, followed by DM/Q 20mg /10 mg twice daily for subsequent 4 weeks, and finally DM/Q 20mg/10mg once daily for 7days.
Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg): DM/Q 20mg/10mg one capsule once daily for 1 week, followed by DM/Q 20mg /10 mg twice daily for subsequent 4 weeks, and finally DM/Q 20mg/10mg once daily for 7days.
Placebo: Placebo once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days. | 9 |
| Placebo, Then Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg) Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg): DM/Q 20mg/10mg one capsule once daily for 1 week, followed by DM/Q 20mg /10 mg twice daily for subsequent 4 weeks, and finally DM/Q 20mg/10mg once daily for 7days.
Placebo: Placebo once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg), Then Placebo | Placebo, Then Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Continuous | 44.8 years STANDARD_DEVIATION 14.2 | 43.1 years STANDARD_DEVIATION 6.3 | 43.9 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 18 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 10 / 20 | 5 / 20 |
| serious Total, serious adverse events | 0 / 20 | 1 / 20 |
Outcome results
Primary
Irritability as Assessed by The Irritability Scale
The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Irritability as Assessed by The Irritability Scale | 18.7 score on a scale | Standard Deviation 10.1 |
| Placebo | Irritability as Assessed by The Irritability Scale | 19.9 score on a scale | Standard Deviation 9.4 |
Primary
Irritability as Assessed by The Irritability Scale.
The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Irritability as Assessed by The Irritability Scale. | 27.5 score on a scale | Standard Deviation 5.8 |
Secondary
Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).
The HADS is a self-report, 14-item scale (7 items relate to anxiety and 7 relate to depression) used to determine the levels of anxiety and depression that a person is experiencing. The total score ranges from 0 to 42 (21 per subscale), with higher scores signifying worse symptoms.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS). | 16.7 score on a scale | Standard Deviation 5.6 |
Secondary
Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).
The HADS is a self-report, 14-item scale (7 items relate to anxiety and 7 relate to depression) used to determine the levels of anxiety and depression that a person is experiencing. The total score ranges from 0 to 42 (21 per subscale), with higher scores signifying worse symptoms.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS). | 10.6 score on a scale | Standard Deviation 6.7 |
| Placebo | Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS). | 11.1 score on a scale | Standard Deviation 8.3 |
Secondary
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.
Caregiver distress associated with the symptom is rated on an anchored 0- to 5-point scale, which total sum ranges from 0 to 60. Higher scores indicate greater caregiver distress related to patient's neuropsychiatric symptoms.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress. | 13.1 score on a scale | Standard Deviation 6.5 |
Secondary
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.
Caregiver distress associated with the symptom is rated on an anchored 0- to 5-point scale, which total sum ranges from 0 to 60. Higher scores indicate greater caregiver distress related to patient's neuropsychiatric symptoms.
Time frame: 4 weeks
Population: Data were not collected for 1 participant in the Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg) arm. Data were not collected for 1 participant in the Placebo arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress. | 7.8 score on a scale | Standard Deviation 5.2 |
| Placebo | Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress. | 11.3 score on a scale | Standard Deviation 7.4 |
Secondary
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.
The NPI-Q is a 12-domain informant-based interview that assesses neuropsychiatric symptoms over the previous month.The total NPI-Q severity score ranges from 0 to 36, with higher scores indicate greater symptoms severity.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score. | 8.2 score on a scale | Standard Deviation 4.5 |
| Placebo | Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score. | 8.6 score on a scale | Standard Deviation 6.2 |
Secondary
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.
The NPI-Q is a 12-domain informant-based interview that assesses neuropsychiatric symptoms over the previous month.The total NPI-Q severity score ranges from 0 to 36, with higher scores indicate greater symptoms severity.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score. | 10.4 score on a scale | Standard Deviation 4.2 |
Secondary
Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s) - Irritability/Aggression Subscale
The PBA-s is a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease. The PBA-s is an 11-item scale rating the frequency and severity of symptoms. The total score for irritability/aggression subscale ranges from 0 to 32, with higher scores indicating greater behavioral symptoms severity.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s) - Irritability/Aggression Subscale | 7.6 score on a scale | Standard Deviation 5.8 |
| Placebo | Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s) - Irritability/Aggression Subscale | 8.7 score on a scale | Standard Deviation 5.7 |
Secondary
Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s). - Irritability/Aggression Subscale
The PBA-s is a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease. The PBA-s is an 11-item scale rating the frequency and severity of symptoms. The total score for irritability/aggression subscale ranges from 0 to 32, with higher scores indicating greater behavioral symptoms severity.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s). - Irritability/Aggression Subscale | 12.9 score on a scale | Standard Deviation 7.2 |
Secondary
Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).
The MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains with a total possible score of 0 to 30 points; a score of 26 or above is considered normal for the general population.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA). | 26.2 score on a scale | Standard Deviation 2.7 |
| Placebo | Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA). | 26.6 score on a scale | Standard Deviation 2.3 |
Secondary
Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).
The MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains with a total possible score of 0 to 30 points; a score of 26 or above is considered normal for the general population.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA). | 25.3 score on a scale | Standard Deviation 3 |
Secondary
Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain.
The UHDRS - cognitive function assessment a phonetic verbal fluency test, the Symbol Digit Modalities Test, and the Stroop Interference Test. These tests do not have a predefined score range, but higher scores indicate better cognitive performance.
Time frame: 4 weeks
Population: Data were not collected for this outcome measure
Secondary
Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain.
The UHDRS - cognitive function assessment a phonetic verbal fluency test, the Symbol Digit Modalities Test, and the Stroop Interference Test. These tests do not have a predefined score range, but higher scores indicate better cognitive performance.
Time frame: Baseline
Population: Data were not collected for this outcome measure
Secondary
Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).
The TFC lists five stages of Huntington's Disease and five levels of function in the domains of workplace, finances, domestic chores, activities of daily living and requirements for unskilled or skilled care. The total TFC score ranges from 0 to 13, with higher scores signifying better functioning.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC). | 11.3 score on a scale | Standard Deviation 1.2 |
Secondary
Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).
The TFC lists five stages of Huntington's Disease and five levels of function in the domains of workplace, finances, domestic chores, activities of daily living and requirements for unskilled or skilled care. The total TFC score ranges from 0 to 13, with higher scores signifying better functioning.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC). | 11.4 score on a scale | Standard Deviation 1.7 |
| Placebo | Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC). | 11.3 score on a scale | Standard Deviation 1.8 |
Secondary
Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).
The TMC comprises 7 of the 31 items in the TMS, which are related to chorea symptoms. The total TMC score ranges from 0 to 28, with higher scores indicating greater chorea severity.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC). | 5.9 score on a scale | Standard Deviation 4.3 |
| Placebo | Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC). | 5.2 score on a scale | Standard Deviation 4 |
Secondary
Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).
The TMC comprises 7 of the 31 items in the TMS, which are related to chorea symptoms. The total TMC score ranges from 0 to 28, with higher scores indicating greater chorea severity.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC). | 6.0 score on a scale | Standard Deviation 3.8 |
Secondary
Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.
The TMS comprises the motor section of the UHDRS, a 31-item subscale that comprehensively evaluates motor aspects of HD. The overall 31 items are each rated from grade 0 (not affected) to grade 4 (most severely affected), resulting in a range of 0-124 points.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS. | 18.7 score on a scale | Standard Deviation 11.8 |
Secondary
Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.
The TMS comprises the motor section of the UHDRS, a 31-item subscale that comprehensively evaluates motor aspects of HD. The overall 31 items are each rated from grade 0 (not affected) to grade 4 (most severely affected), resulting in a range of 0-124 points.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Pre-Randomization | Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS. | 19.3 score on a scale | Standard Deviation 11.8 |
| Placebo | Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS. | 18.7 score on a scale | Standard Deviation 11.5 |
Secondary
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.
The questions 6-10 of the C-SSRS are related to suicidal behavior, and the outcome is a simple yes/no response. Suicidal behavior occurs if the patient answers a yes at any time during treatment to any one of the five suicidal behavior questions (Categories 6-10) on the C-SSRS.
Time frame: Baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Study Participants Pre-Randomization | Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior. | 0 Participants |
Secondary
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.
The questions 6-10 of the C-SSRS are related to suicidal behavior, and the outcome is a simple yes/no response. Suicidal behavior occurs if the patient answers a yes at any time during treatment to any one of the five suicidal behavior questions (Categories 6-10) on the C-SSRS.
Time frame: 4 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Study Participants Pre-Randomization | Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior. | 0 Participants |
| Placebo | Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior. | 0 Participants |
Secondary
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation
The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses. The first part (Items 1-5) rates an individual's degree of suicidal ideation on a 0-5 scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent and behaviors. The C-SSRS outcomes are categories and have binary responses (yes/no). Suicidal ideation is considered when the patient responds a yes answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5) on the C-SSRS. The sum of the 5 intensity item scores create a total score (range 0 to 25) to represent the intensity rating (higher scores indicate more severe suicidal ideation).
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Study Participants Pre-Randomization | Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation | 0 Participants |
| Placebo | Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation | 0 Participants |
Secondary
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation.
The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses. The first part (Items 1-5) rates an individual's degree of suicidal ideation on a 0-5 scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent and behaviors. The C-SSRS outcomes are categories and have binary responses (yes/no). Suicidal ideation is considered when the patient responds a yes answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5) on the C-SSRS. The sum of the 5 intensity item scores create a total score (range 0 to 25) to represent the intensity rating (higher scores indicate more severe suicidal ideation).
Time frame: Baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Study Participants Pre-Randomization | Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation. | 0 Participants |
Secondary
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I).
The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication.
Time frame: 4 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Minimally improved | 3 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Much improved | 4 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | No change | 8 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Much worse | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Not analyzed | 1 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Minimally worse | 1 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Very much improved | 1 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Very much worse | 0 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Much improved | 5 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | No change | 9 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Minimally worse | 0 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Much worse | 2 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Minimally improved | 0 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Very much worse | 0 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Not analyzed | 1 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). | Very much improved | 1 Participants |
Secondary
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S).
The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. The CGI is a 3-item observer-rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and therapeutic response. The scale ranges from 1-7, with higher scores indicating worse outcomes.
Time frame: 4 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Borderline ill | 1 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Markedly ill | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Severely ill | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Normal | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Mildly ill | 2 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Moderately ill | 14 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Extremely ill | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Not analyzed | 1 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Borderline ill | 4 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Moderately ill | 9 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Markedly ill | 1 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Mildly ill | 2 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Extremely ill | 0 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Severely ill | 0 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Not analyzed | 2 Participants |
| Placebo | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Normal | 0 Participants |
Secondary
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S).
The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication.
Time frame: Baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Normal | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Borderline ill | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Mildly ill | 3 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Moderately ill | 11 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Markedly ill | 3 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Severely ill | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Extremely ill | 0 Participants |
| All Study Participants Pre-Randomization | Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). | Not analyzed | 1 Participants |