Trial Outcomes & Findings for Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease (NCT NCT03854019)

NCT ID: NCT03854019

Last Updated: 2024-01-05

Results Overview

The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 20 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2024-01-05

Participant Flow

Participant milestones

Measure	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.	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.
First Intervention (4 Weeks) STARTED	10	10
First Intervention (4 Weeks) COMPLETED	9	9
First Intervention (4 Weeks) NOT COMPLETED	1	1
Washout (1 Week) STARTED	9	9
Washout (1 Week) COMPLETED	9	9
Washout (1 Week) NOT COMPLETED	0	0
Second Intervention (4 Weeks) STARTED	9	9
Second Intervention (4 Weeks) COMPLETED	9	9
Second Intervention (4 Weeks) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease

Baseline characteristics by cohort

Measure	Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg), Then Placebo n=9 Participants 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.	Placebo, Then Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg) n=9 Participants 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.	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	44.8 years STANDARD_DEVIATION 14.2 • n=5 Participants	43.1 years STANDARD_DEVIATION 6.3 • n=7 Participants	43.9 years STANDARD_DEVIATION 11.7 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Irritability as Assessed by The Irritability Scale.	27.5 score on a scale Standard Deviation 5.8	—

PRIMARY outcome

Timeframe: 4 weeks

The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Irritability as Assessed by The Irritability Scale	18.7 score on a scale Standard Deviation 10.1	19.9 score on a scale Standard Deviation 9.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).	16.7 score on a scale Standard Deviation 5.6	—

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).	10.6 score on a scale Standard Deviation 6.7	11.1 score on a scale Standard Deviation 8.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.	10.4 score on a scale Standard Deviation 4.2	—

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.	8.2 score on a scale Standard Deviation 4.5	8.6 score on a scale Standard Deviation 6.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.	13.1 score on a scale Standard Deviation 6.5	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=17 Participants All Study Participants Pre-Randomization	Placebo n=17 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.	7.8 score on a scale Standard Deviation 5.2	11.3 score on a scale Standard Deviation 7.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
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 outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
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	8.7 score on a scale Standard Deviation 5.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.	18.7 score on a scale Standard Deviation 11.8	—

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.	19.3 score on a scale Standard Deviation 11.8	18.7 score on a scale Standard Deviation 11.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).	6.0 score on a scale Standard Deviation 3.8	—

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).	5.9 score on a scale Standard Deviation 4.3	5.2 score on a scale Standard Deviation 4.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).	11.3 score on a scale Standard Deviation 1.2	—

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).	11.4 score on a scale Standard Deviation 1.7	11.3 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation.	0 Participants	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.	0 Participants	—

SECONDARY outcome

Timeframe: 4 Weeks

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).	25.3 score on a scale Standard Deviation 3.0	—

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).	26.2 score on a scale Standard Deviation 2.7	26.6 score on a scale Standard Deviation 2.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Moderately ill	11 Participants	—
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Normal	0 Participants	—
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Borderline ill	0 Participants	—
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Mildly ill	3 Participants	—
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Markedly ill	3 Participants	—
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Severely ill	0 Participants	—
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Extremely ill	0 Participants	—
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Not analyzed	1 Participants	—

SECONDARY outcome

Timeframe: 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. 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Normal	0 Participants	0 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Borderline ill	1 Participants	4 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Mildly ill	2 Participants	2 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Moderately ill	14 Participants	9 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Markedly ill	0 Participants	1 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Severely ill	0 Participants	0 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Extremely ill	0 Participants	0 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). Not analyzed	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Study Participants Pre-Randomization n=18 Participants All Study Participants Pre-Randomization	Placebo n=18 Participants Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). Very much improved	1 Participants	1 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). Much improved	4 Participants	5 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). Minimally improved	3 Participants	0 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). No change	8 Participants	9 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). Minimally worse	1 Participants	0 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). Much worse	0 Participants	2 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). Very much worse	0 Participants	0 Participants
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). Not analyzed	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline

Population: Data were not collected for this outcome measure

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 weeks

Population: Data were not collected for this outcome measure

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.

Outcome measures

Outcome data not reported

Adverse Events

Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg) n=20 participants at risk 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.	Placebo n=20 participants at risk Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
General disorders Hospitalization for motorcycle accident	0.00% 0/20 • 13 weeks	5.0% 1/20 • 13 weeks

Other adverse events

Measure	Dextromethorphan/Quinidine 20mg/10mg (DM/Q 20mg/10mg) n=20 participants at risk 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.	Placebo n=20 participants at risk Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
General disorders Insomnia	5.0% 1/20 • 13 weeks	5.0% 1/20 • 13 weeks
General disorders Headaches	10.0% 2/20 • 13 weeks	0.00% 0/20 • 13 weeks
Gastrointestinal disorders Diarrhea	0.00% 0/20 • 13 weeks	5.0% 1/20 • 13 weeks
Infections and infestations Fingernail infection	0.00% 0/20 • 13 weeks	5.0% 1/20 • 13 weeks
General disorders Nausea	5.0% 1/20 • 13 weeks	0.00% 0/20 • 13 weeks
General disorders Dizziness	5.0% 1/20 • 13 weeks	0.00% 0/20 • 13 weeks
General disorders Loss weight/decreased appetite	5.0% 1/20 • 13 weeks	0.00% 0/20 • 13 weeks
General disorders Increased libido	5.0% 1/20 • 13 weeks	0.00% 0/20 • 13 weeks
General disorders Decreased libido	0.00% 0/20 • 13 weeks	5.0% 1/20 • 13 weeks
General disorders decline in mood	0.00% 0/20 • 13 weeks	5.0% 1/20 • 13 weeks
General disorders Primary care physician (PCP) prescribed medication for high blood pressure	5.0% 1/20 • 13 weeks	0.00% 0/20 • 13 weeks
General disorders Increased apathy	5.0% 1/20 • 13 weeks	0.00% 0/20 • 13 weeks
Infections and infestations COVID-19	5.0% 1/20 • 13 weeks	0.00% 0/20 • 13 weeks

Additional Information

Erin Furr Stimming, MD

The University of Texas Health Science Center at Houston

Phone: 713-500-7033

Email: Erin.E.Furr@uth.tmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place