Safety, Tolerability and Effectiveness of Nuedexta in the Treatment of Pseudobulbar Affect (PBA)

Study Overview
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Brief Summary
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The objectives of the study are to evaluate the safety, tolerability, and effectiveness of NUEDEXTA capsules containing 20 mg DM (Dextromethorphan)/10 mg Q (Quinidine) for treatment of Pseudobulbar Affect (PBA) in patients with prevalent conditions such as dementia, stroke, and traumatic brain injury (TBI)over a 12 week period.

Detailed Description
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This will be an Open-label, Multicenter, study in patients with PBA and dementia, stroke or TBI. Patients with a clinical diagnosis of PBA and who meet all other inclusion and exclusion criteria will be eligible to participate and receive NUEDEXTA for 12 weeks. Males and females patients with a minimum age of 18 years, a clinical diagnosis of Pseudobulbar Affect and a documented diagnosis of neurologic disease or brain injury, will be enrolled in this study. The primary effectiveness endpoint is the mean change in the Center for Neurologic Study-Lability scale (CNS-LS). Secondary objectives include measures to evaluate treatment outcomes.

Official Title
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A Study to Assess the Safety, Tolerability and Effectiveness of Nuedexta (Dextromethorphan 20 mg/Quinidine 10 mg) in the Treatment of Pseudobulbar Affect (PBA)

Conditions
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Stroke, Pseudobulbar Affect (PBA), Dementia, Traumatic Brain Injury (TBI)

Intervention / Treatment
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* Drug: Nuedexta (DM 20 mg/Q 10 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Center for Neurologic Study-Lability Scale (CNS-LS)score of 13 or greater Clinical diagnosis of Pseudobulbar Affect (PBA) Documentation of Neurologic disease or brain injury Exclusion Criteria: Unstable neurologic disease Severe dementia Stroke within 3 months Penetrating TBI Contraindications to Nuedexta Severe Depressive Disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Nuedexta (DM 20 mg/Q 10 mg)<br>Single Arm, Open Label Dosing with Nuedexta (DM 20 mg/Q 10 mg) | Drug: Nuedexta (DM 20 mg/Q 10 mg)<br>* Single Arm, Open-Label Dosing with Nuedexta (DM 20 mg/Q 10 mg)<br>* Other names: Nuedexta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Center for Neurologic Study-Lability Scale (CNS-LS) Score at Day 90 | The CNS-LS was a seven-item, self-administered questionnaire, completed by the participant or participant's caregiver that provided a quantitative measure of the perceived frequency and severity of Pseudobulbar Affect (PBA) episodes. It consisted of two subscales measuring labile laughter (four items) and labile crying (three items). Each item was rated on a scale from 1 (applies never) to 5 (applies most of the time). The total score was calculated as the sum of the item values that resulted in a score ranging from 7 (no symptoms) to 35 (maximum symptom severity and frequency). A single continuous variable was created for the reported time point. The change in CNS-LS was calculated as the score from the Day 90 assessment minus the Baseline CNS-LS measure. A negative change represented a decrease in CNS-LS score over time following the baseline assessment indicating a perceived decrease in frequency and severity of PBA episodes. | Day 90 (Final visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Center for Neurologic Study-Lability Scale (CNS-LS) Score at Day 30 | The CNS-LS was a seven-item, self-administered questionnaire, completed by the participant or participant's caregiver that provided a quantitative measure of the perceived frequency and severity of Pseudobulbar Affect (PBA) episodes. It consisted of two subscales measuring labile laughter (four items) and labile crying (three items). Each item was rated on a scale from 1 (applies never) to 5 (applies most of the time). The total score was calculated as the sum of the item values that resulted in a score ranging from 7 (no symptoms) to 35 (maximum symptom severity and frequency). A single continuous variable was created for the reported time point. The change in CNS-LS was calculated as the score from the Day 30 assessment minus the Baseline CNS-LS measure. A negative change represented a decrease in CNS-LS score over time following the baseline assessment indicating a perceived decrease in frequency and severity of PBA episodes. | Day 30 | 
| Mean Pseudobulbar Affect (PBA) Episode Count Per Week by Visit | PBA episode count was an investigator assessed measure in which the participant/participant's daytime caregiver was asked to identify, count and recall the total episodes of exaggerated/uncontrollable laughing or crying over the previous 7 days (prior to visit) at Baseline (Day 1), Day 30 (Visit 1), and Day 90 (Final visit). The response categories for this question were: 0, 1- 2, 3-5, 6-10, >10. The original responses from participants were converted to estimate the continuous number of PBA episodes by taking the mid-point of the original response ranges and multiplying that value by 7. Data is presented as mean PBA count per week. | Baseline (Day 1), Day 30 (Visit 1), and Day 90 (Final visit) | 
| Percentage of Participants With PBA Remission | PBA remission was defined as participants with one or more episodes reported at the baseline (Day 1) visit and zero episodes reported at the Day 30 (Visit 1) or Day 90 (Final visit). Data is reported as percentage of participants with no reported episodes over the previous 7 days (prior to visit) at Day 30 (Visit 1) and Day 90 (Final visit). | Day 30 (Visit 1) and Day 90 (Final visit) | 
| Percentage Change From Baseline in PBA Episode Count Per Week | The change from the baseline PBA rate was measured using Mixed Effects Poisson Regression Model (adjusted for gender and age [≤ 65 years]). | Day 30 (Visit 1) and Day 90 (Final visit) | 
| Percentage of Participants With ≥ 50% Reduction in PBA Episode Count Per Week | Data is reported as the percentage of participants with ≥ 50% reduction in PBA episode count/week. | Day 30 (Visit 1) and Day 90 (Final visit) | 
| Percentage of Participants With ≥ 75% Reduction in PBA Episode Count Per Week | Data is reported as the percentage of participants with ≥ 75% reduction in PBA episode count/week. | Day 30 (Visit 1) and Day 90 (Final visit) | 
| Mean Change From Baseline in Quality of Life Visual Analog Scale (QOL-VAS) Score at Day 90 | The QOL-VAS, a participant reported scale of quality of life (QOL) was used to measure the impact of PBA episodes on the participant's QOL over the previous 7 days (prior to visit) at Baseline (Day 1) and Day 90 (Final visit). The assessment was completed by a participant placing a mark on a horizontal line that extends from 0 not (affected) at all to 10 significantly (affected). The participant's mark was measured and recorded at each time point. The change in QOL-VAS score from baseline to day 90 visit, defined as the day 90 score minus the baseline score, was analyzed. Data is reported as mean QOL-VAS score; a positive change in score represented an increase in participant's quality of life. | Day 90 (Final visit) | 
| Percentage of Participants With Clinical Global Impression-Change (CGI-C) Score at Day 90 | CGI-C, an investigator-assessed scale was used to measure the overall treatment response. CGI-C, a 7-point (1-7) scale was rated as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. Data is presented as percentage of participants with CGI-C score at Day 90. Percentages within a measure may not sum to 100.0 due to rounding. Percentages use the count of participants with non-missing data as the denominator. | Day 90 (Final visit) | 
| Percentage of Participants With Patient Global Impression-Change (PGI-C) Score at Day 90 | PGI-C, a participant/participant's caregiver-assessed scale was used to measure participant overall treatment response. PGI-C, a 7-point (1-7) scale was rated as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. Data is presented as percentage of participants with PGI-C score at Day 90. Percentages within a measure may not sum to 100.0 due to rounding. Percentages use the count of participants with non-missing data as the denominator. | Day 90 (Final visit) | 
| Percentage of Participants With Treatment Satisfaction Survey | The treatment satisfaction survey was a 5 point single question survey that was administered by the site staff to the participant/participant's caregiver. Participants were asked to rate their response to treatment satisfaction as: very dissatisfied, somewhat dissatisfied, neither satisfied nor dissatisfied, somewhat satisfied, and very satisfied. Data is presented as percentage of participants with treatment satisfaction at Day 90. Percentages within a measure may not sum to 100.0 due to rounding. Percentages use the count of participants with non-missing data as the denominator. | Day 90 (Final visit) | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs (defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) and SAEs (defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening [ie, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death], required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was as a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug) were assessed during the study. | From signing of informed consent up to 30 days after receiving the last dose of study drug or up to approximately 120 days |