Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nuedexta (DM 20 mg/Q 10 mg) | Other | Single Arm, Open Label Dosing with Nuedexta (DM 20 mg/Q 10 mg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nuedexta (DM 20 mg/Q 10 mg) | Drug | Single Arm, Open-Label Dosing with Nuedexta (DM 20 mg/Q 10 mg) |
|
| 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) |
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pensacola | Florida | 32503 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29477412 | Derived | Hammond FM, Sauve W, Ledon F, Davis C, Formella AE. Safety, Tolerability, and Effectiveness of Dextromethorphan/Quinidine for Pseudobulbar Affect Among Study Participants With Traumatic Brain Injury: Results From the PRISM-II Open Label Study. PM R. 2018 Oct;10(10):993-1003. doi: 10.1016/j.pmrj.2018.02.010. Epub 2018 Feb 23. | |
| 27276999 |
Not provided
Not provided
A total of 394 participants were screened of which 367 participants were enrolled in the study; 134 in the dementia cohort, 113 in the stroke cohort, and 120 in the traumatic brain injury (TBI) cohort.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Dextromethorphan Hydrobromide 20 mg + Quinidine Sulfate 10 mg | Participants who received fixed-dose combination of 20 milligram (mg) dextromethorphan hydrobromide and 10 mg quinidine sulfate, orally once daily in the morning for the first week of the study, and twice daily (every 12 hours) for the remaining 11 weeks of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Dextromethorphan Hydrobromide 20 mg + Quinidine Sulfate 10 mg | Participants who received fixed-dose combination of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate, orally once daily in the morning for the first week of the study, and twice daily (every 12 hours) for the remaining 11 weeks of the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The analysis was performed using the Modified Intent-to-treat (mITT) Population, defined as all participants who met all inclusion criteria, with a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with CNS-LS. | Posted | Mean | Standard Deviation | Units on a scale | Day 90 (Final visit) |
From signing of informed consent up to 30 days after receiving the last dose of study drug or up to approximately 120 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Overall | Participants with dementia, stroke, and traumatic brain injury who received fixed-dose combination of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate, orally once daily in the morning for the first week of the study, and twice daily (every 12 hours) for the remaining 11 weeks of the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nadine Knowles; Executive Director, Research & Development Operations | Avanir Pharmaceuticals | 1-949-268-8972 | nknowles@avanir.com |
Not provided
| ID | Term |
|---|---|
| D020521 | Stroke |
| D003704 | Dementia |
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C507057 | dextromethorphan - quinidine combination |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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 |
| Hammond FM, Alexander DN, Cutler AJ, D'Amico S, Doody RS, Sauve W, Zorowitz RD, Davis CS, Shin P, Ledon F, Yonan C, Formella AE, Siffert J. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurol. 2016 Jun 9;16:89. doi: 10.1186/s12883-016-0609-0. |
| 26471212 | Derived | Doody RS, D'Amico S, Cutler AJ, Davis CS, Shin P, Ledon F, Yonan C, Siffert J. An open-label study to assess safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in dementia: PRISM II results. CNS Spectr. 2016 Dec;21(6):450-459. doi: 10.1017/S1092852915000620. Epub 2015 Oct 16. |
| Investigator Decision |
|
| Lack of Efficacy |
|
| Lost to Follow-up |
|
| Other |
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
|
|
| Secondary | 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. | The analysis was performed using the mITT population, defined as all participants who met all inclusion criteria, with a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with CNS-LS. | Posted | Mean | Standard Deviation | Units on a scale | Day 30 |
|
|
|
|
| Secondary | 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. | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with PBA episode. | Posted | Mean | Standard Deviation | Count/week | Baseline (Day 1), Day 30 (Visit 1), and Day 90 (Final visit) |
|
|
|
|
| Secondary | 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). | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with PBA episode. | Posted | Number | Percentage of participants | Day 30 (Visit 1) and Day 90 (Final visit) |
|
|
|
| Secondary | 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]). | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with PBA episode. | Posted | Mean | 95% Confidence Interval | percent change | Day 30 (Visit 1) and Day 90 (Final visit) |
|
|
|
|
| Secondary | 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. | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with PBA episode. | Posted | Number | Percentage of participants | Day 30 (Visit 1) and Day 90 (Final visit) |
|
|
|
| Secondary | 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. | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with PBA episode. | Posted | Number | Percentage of participants | Day 30 (Visit 1) and Day 90 (Final visit) |
|
|
|
| Secondary | 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. | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with QOL-VAS. | Posted | Mean | Standard Deviation | Units on a scale | Day 90 (Final visit) |
|
|
|
|
| Secondary | 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. | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with CGI-C. | Posted | Number | Percentage of participants | Day 90 (Final visit) |
|
|
|
| Secondary | 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. | The analysis population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with PGI-C. | Posted | Number | Percentage of participants | Day 90 (Final visit) |
|
|
|
| Secondary | 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. | The mITT Population consisted of all participants who met all inclusion criteria, including a score of at least 13 on the CNS-LS, who received at least 1 dose of study drug, and who had at least 1 post-baseline efficacy measurement with CNS-LS. | Posted | Number | Percentage of participants | Day 90 (Final visit) |
|
|
|
| Secondary | 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. | The analysis was performed using the safety population that consisted of all enrolled patients who received at least 1 dose of study drug. | Posted | Number | Participants | From signing of informed consent up to 30 days after receiving the last dose of study drug or up to approximately 120 days |
|
|
|
| 23 |
| 367 |
| 35 |
| 367 |
| EG001 | Dementia | Participants with dementia who received fixed-dose combination of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate, orally once daily in the morning for the first week of the study, and twice daily (every 12 hours) for the remaining 11 weeks of the study. | 14 | 134 | 15 | 134 |
| EG002 | Stroke | Participants with stroke who received fixed-dose combination of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate, orally once daily in the morning for the first week of the study, and twice daily (every 12 hours) for the remaining 11 weeks of the study. | 5 | 113 | 9 | 113 |
| EG003 | Traumatic Brain Injury | Participants with traumatic brain injury who received fixed-dose combination of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate, orally once daily in the morning for the first week of the study, and twice daily (every 12 hours) for the remaining 11 weeks of the study. | 4 | 120 | 11 | 120 |
| Cardiac arrest | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
|
| Myocardial ischaemia | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Osteomyelitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Prostate infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Intentional overdose | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Carotid artery stenosis | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Toxic encephalopathy | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Transient ischaemic attack | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Paranoia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
Not provided
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001930 | Brain Injuries |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| Superiority or Other |
| One-sample t-test | <0.0001 | Superiority or Other |
| One-sample t-test | <0.0001 | Superiority or Other |
| Day 30 (n= 296, 108, 102, 86) |
|
| Day 90 (n= 260, 102, 92, 66) |
|
| <0.0001 |
| Superiority or Other |
| Day 30 versus Baseline | One-sample t-test | <0.0001 | Superiority or Other |
| Day 90 assessment | One-sample t-test | <0.0001 | Superiority or Other |
| Day 30 versus Baseline | One-sample t-test | <0.0001 | Superiority or Other |
| Day 90 versus Baseline | One-sample t-test | <0.0001 | Superiority or Other |
| Day 30 versus Baseline | One-sample t-test | <0.0001 | Superiority or Other |
| Day 90 versus Baseline | One-sample t-test | <0.0001 | Superiority or Other |
| Day 90 (n= 260, 102, 92, 66) |
|
| Day 90 (n=260, 102, 92, 66) |
|
Day 90 assessment
| Mixed Effects Poisson Regression Model |
| <0.0001 |
| Incidence Rate Ratio |
| 0.277 |
| Standard Error of the Mean |
| 0.028 |
| 2-Sided |
| 95 |
| 0.262 |
| 0.293 |
Number of observations = 854, Number of participants = 298 |
| Superiority or Other |
| Day 30 assessment | Mixed Effects Poisson Regression Model | <0.0001 | Incidence Rate Ratio | 0.500 | Standard Error of the Mean | 0.033 | 2-Sided | 95 | 0.469 | 0.534 | Number of observations = 318, Number of participants = 108 | Superiority or Other |
| Day 90 assessment | Mixed Effects Poisson Regression Model | <0.0001 | Incidence Rate Ratio | 0.323 | Standard Error of the Mean | 0.039 | 2-Sided | 95 | 0.299 | 0.349 | Number of observations = 318, Number of participants = 108 | Superiority or Other |
| Day 30 assessment | Mixed Effects Poisson Regression Model | <0.0001 | Incidence Rate Ratio | 0.351 | Standard Error of the Mean | 0.044 | 2-Sided | 95 | 0.323 | 0.383 | Number of observations = 297, Number of participants = 103 | Superiority or Other |
| Day 90 assessment | Mixed Effects Poisson Regression Model | <0.0001 | Incidence Rate Ratio | 0.255 | Standard Error of the Mean | 0.051 | 2-Sided | 95 | 0.231 | 0.282 | Number of observations = 297, Number of participants = 103 | Superiority or Other |
| Day 30 assessment | Mixed Effects Poisson Regression Model | <0.0001 | Incidence Rate Ratio | 0.387 | Standard Error of the Mean | 0.048 | 2-Sided | 95 | 0.352 | 0.425 | Number of observations = 239, Number of participants = 87 | Superiority or Other |
| Day 90 assessment | Mixed Effects Poisson Regression Model | <0.0001 | Incidence Rate Ratio | 0.215 | Standard Error of the Mean | 0.066 | 2-Sided | 95 | 0.189 | 0.245 | Number of observations = 239, Number of participants = 87 | Superiority or Other |
| Day 90 (n= 254, 101, 90, 63) |
|
| Day 90 (n= 254, 101, 90, 63) |
|
| Superiority or Other |
| One-sample t-test | <0.0001 | Superiority or Other |
| One-sample t-test | <0.0001 | Superiority or Other |
| Much improved |
|
| Minimally improved |
|
| No change |
|
| Minimally worse |
|
| Much worse |
|
| Veru much worse |
|
| Much improved |
|
| Minimally improved |
|
| No change |
|
| Minimally worse |
|
| Much worse |
|
| Veru much worse |
|
| Somewhat dissatisfied |
|
| Neither satisfied nor dissatisfied |
|
| Somewhat satisfied |
|
| Very satisfied |
|
| SAEs |
|