Pseudobulbar Affect (PBA)
Conditions
Keywords
Amyotrophic Lateral Sclerosis (Lou Gehrig's disease, ALS), Multiple Sclerosis (MS)
Brief summary
Objectives of the study are to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 (capsules containing either 30 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate \[AVP-923-30\] or 20 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate \[AVP-923-20\]) when compared to placebo, for the treatment of PBA in a population of patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) over a 12-week period. An additional objective is to determine the pharmacokinetic parameters of the two different doses of AVP-923 in a subset of the study population. Pseudobulbar Affect (PBA) is a condition characterized by involuntary, sudden and frequent episodes of laughing and/or crying out of proportion or incongruous to the underlying emotion of happiness or sadness Other terms used to describe this condition include emotional lability, emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism, and pathological laughing and crying. The outbursts can occur spontaneously or in response to provocative stimuli such as questions or events. A body of evidence suggests that PBA can be modulated through pharmacologic intervention. Dextromethorphan (DM) is a low-affinity uncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, reducing the level of excitatory activity. DM also acts at the phencyclidine-binding site, which is part of the NMDA receptor complex. DM is a sigma receptor agonist, suppressing the release of excitatory neurotransmitters. Quinidine (Q) is a known potent inhibitor of cytochrome P450 2D6 (CYP2D6), that decreases the metabolism of dextromethorphan and helps to achieve sustained and therapeutic levels of this drug.
Interventions
DRUGdextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg
Dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) capsules (AVP-923 capsules), containing DM 20 mg/ Q 10 mg, taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period
DRUGdextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg
Dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) capsules (AVP-923 capsules), containing DM 30 mg/ Q 10 mg taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period
DRUGPlacebo
Placebo capsules (identical in appearance to AVP-923 capsules being studied in this trial), taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period
Sponsors
Syneos Health
Avanir Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * The patient has a diagnosis of Amyotrophic Lateral Sclerosis (according to El Escorial Criteria, WFN, 1998) and the time from diagnosis of ALS is not be longer than 30 months, or the patient has a diagnosis of multiple sclerosis or probable multiple sclerosis (according to McDonald criteria, 2001) * The patient has a clinical history and clinical relevant symptoms of Pseudobulbar Affect (PBA) * CNS-LS score at baseline is 13 or greater Main
Exclusion criteria
* Patients with myasthenia gravis * Any personal history of complete heart block, QTc prolongation, or torsades de pointes * Any family history of congenital QT interval prolongation syndrome * Patients with known sensitivity to quinidine, dextromethorphan or opiate drugs (codeine, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PBA Episode Rate Ratio (Post/Pre), Regression Adjusted | Baseline to Day 84 | Episodes were counted each day and recorded in a daily diary. The outcome measure is the ratio of the episode rate over the 84-day treatment period to the rate during the baseline period, adjusted for study site, and underlying disease using longitudinal negative binomial regression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | Baseline to Day 84 | The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe). |
| Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | Baseline to Day 84 | The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe). |
| Mean Change From Baseline in CNS-LS Total Score by Visit | Baseline, Day 15, Day 29, Day 57, Day 84 | Center for Neurologic Studies-Lability Scale (CNS-LS) is an instrument for the measurement of PBA that has been validated for the use in patients with ALS and MS. It is a 7-item self-report questionnaire that measures the frequency and severity of PBA episodes, including assessments of labile laughter and labile tearfulness,and provides a score for total PBA (total score can range from 7-35). The following 5-point scoring was used: 1=Applies never, 2=Applies rarely, 3=Applies occasionally, 4=Applies frequently, 5=Applies most of the time. A score of 13 or higher may suggest PBA, and the higher the score the more severe the episodes. |
| Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score | Baseline and Day 84 | The BDI-II is a 21-item self report instrument intended to assess the existence and severity of symptoms of depression, summed to give a single score. The BDI-II uses a 4-point for each item ranging from 0 to 3. A total score of 0-13 is considered minimal range, 14 to 19 is mild, 20 to 28 is moderate, and 29 to 63 is severe. |
| Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects | Baseline, Day 15, Day 29, Day 57, Day 84 | Subjects with MS were instructed to also record daily the pain they experienced using the PRS. After evaluating the subject's ability to comply with these requirements, the investigator determined if a caregiver should complete the study diary and assessments. Subjects rated their pain over the past 12 hours on a scale of 0 to 10 (0=none, 10=worst pain ever experienced). |
| Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Baseline and Day 84 | The SF-36 is designed to examine a person's perceived health status. The SF-36 includes one multi-item scale measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health. Answers to each question are scored and summed to produce raw scale scores for each health concept which are then transformed to a 0 - 100 scale, a high score defining a more favorable health state. An aggregate summary measure is calculated by averaging the scores from the eight health concepts. |
Countries
Argentina, Brazil, United States
Participant flow
Recruitment details
Subjects diagnosed with pseudobulbar affect (PBA) secondary to amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).
Participants by arm
| Arm | Count |
|---|---|
| AVP-923-30 AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily. | 110 |
| AVP-923-20 AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily. | 107 |
| Placebo Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily. | 109 |
| Total | 326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Phase | Adverse Event | 1 | 5 | 0 |
| Double-Blind Phase | Exacerbation of MS symptoms | 1 | 0 | 1 |
| Double-Blind Phase | Lost to Follow-up | 1 | 3 | 2 |
| Double-Blind Phase | Medication refusal due to AE | 2 | 2 | 0 |
| Double-Blind Phase | Other | 0 | 2 | 3 |
| Double-Blind Phase | Protocol Violation | 0 | 2 | 1 |
| Double-Blind Phase | Serious Adverse Event (AE) | 2 | 3 | 1 |
| Double-Blind Phase | Withdrawal by Subject | 2 | 2 | 7 |
| Open-Label Extension Phase | Adverse Event | 3 | 0 | 0 |
| Open-Label Extension Phase | Exacerbation of MS symptoms | 2 | 0 | 0 |
| Open-Label Extension Phase | Lost to Follow-up | 1 | 0 | 0 |
| Open-Label Extension Phase | Other | 2 | 0 | 0 |
| Open-Label Extension Phase | Protocol Violation | 2 | 0 | 0 |
| Open-Label Extension Phase | Serious Adverse Event | 5 | 0 | 0 |
| Open-Label Extension Phase | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | AVP-923-30 | AVP-923-20 | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 53.08 Years STANDARD_DEVIATION 11.016 | 50.81 Years STANDARD_DEVIATION 11.114 | 50.27 Years STANDARD_DEVIATION 11.939 | 51.39 Years STANDARD_DEVIATION 11.356 |
| Sex: Female, Male Female | 64 Participants | 54 Participants | 59 Participants | 177 Participants |
| Sex: Female, Male Male | 46 Participants | 53 Participants | 50 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 66 / 110 | 65 / 107 | 63 / 109 | 123 / 253 |
| serious Total, serious adverse events | 8 / 110 | 9 / 107 | 10 / 109 | 14 / 253 |
Outcome results
Primary
PBA Episode Rate Ratio (Post/Pre), Regression Adjusted
Episodes were counted each day and recorded in a daily diary. The outcome measure is the ratio of the episode rate over the 84-day treatment period to the rate during the baseline period, adjusted for study site, and underlying disease using longitudinal negative binomial regression.
Time frame: Baseline to Day 84
Population: Intent-to-Treat (ITT) population - included all randomized subjects for the double-blind phase and all enrolled subjects for the open-label extension phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AVP-923-30 | PBA Episode Rate Ratio (Post/Pre), Regression Adjusted | 0.247 Unit-free (ratio of episodes/week) | 95% Confidence Interval 3.447 |
| AVP-923-20 | PBA Episode Rate Ratio (Post/Pre), Regression Adjusted | 0.237 Unit-free (ratio of episodes/week) | 95% Confidence Interval 6.048 |
| Placebo | PBA Episode Rate Ratio (Post/Pre), Regression Adjusted | 0.465 Unit-free (ratio of episodes/week) | 95% Confidence Interval 6.642 |
Comparison: Analysis of PBA episode rates used longitudinal negative binomial regression with treatment, period, diagnosis and study site to estimate pre-post changes in log mean episode rate for each treatment group. Null hypothesis of equal pre-post episode rate reductions were tested: AVP-923-30/placebo = 1.p-value: <0.000195% CI: [0.4939, 0.5714]Regression, Longitudinal neg. binomial
Comparison: Analysis of PBA episode rates used longitudinal negative binomial regression with treatment, period, diagnosis and study site to estimate pre-post changes in log mean episode rate for each treatment group. Null hypothesis of equal pre-post episode rate reductions were tested: AVP-923-20/placebo = 1.p-value: <0.000195% CI: [0.4755, 0.5477]Regression, Longitudinal neg. binomial
Secondary
Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score
The BDI-II is a 21-item self report instrument intended to assess the existence and severity of symptoms of depression, summed to give a single score. The BDI-II uses a 4-point for each item ranging from 0 to 3. A total score of 0-13 is considered minimal range, 14 to 19 is mild, 20 to 28 is moderate, and 29 to 63 is severe.
Time frame: Baseline and Day 84
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVP-923-30 | Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score | -1.59 Scores on a Scale | Standard Deviation 5.294 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score | -1.03 Scores on a Scale | Standard Deviation 5.183 |
| Placebo | Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score | -0.02 Scores on a Scale | Standard Deviation 6.32 |
Secondary
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
The SF-36 is designed to examine a person's perceived health status. The SF-36 includes one multi-item scale measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health. Answers to each question are scored and summed to produce raw scale scores for each health concept which are then transformed to a 0 - 100 scale, a high score defining a more favorable health state. An aggregate summary measure is calculated by averaging the scores from the eight health concepts.
Time frame: Baseline and Day 84
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Mental Health Scale | 5.53 Scores on a Scale | Standard Deviation 17.067 |
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Physical Functioning Scale | -0.90 Scores on a Scale | Standard Deviation 17.336 |
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | General Health Scale | -1.47 Scores on a Scale | Standard Deviation 17.273 |
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Role Emotional Scale | 11.55 Scores on a Scale | Standard Deviation 47.711 |
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Role Physical Scale | 3.47 Scores on a Scale | Standard Deviation 36.747 |
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Vitality Scale | -0.90 Scores on a Scale | Standard Deviation 17.336 |
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Bodily Pain Scale | 4.09 Scores on a Scale | Standard Deviation 20.861 |
| AVP-923-30 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Social Functioning Scale | 9.34 Scores on a Scale | Standard Deviation 25.105 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Role Physical Scale | -4.26 Scores on a Scale | Standard Deviation 39.764 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Social Functioning Scale | 1.42 Scores on a Scale | Standard Deviation 28.577 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Physical Functioning Scale | -5.30 Scores on a Scale | Standard Deviation 15.652 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Role Emotional Scale | -1.81 Scores on a Scale | Standard Deviation 45.924 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Mental Health Scale | 3.09 Scores on a Scale | Standard Deviation 16.877 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Bodily Pain Scale | 5.84 Scores on a Scale | Standard Deviation 20.437 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | General Health Scale | -2.95 Scores on a Scale | Standard Deviation 16.266 |
| AVP-923-20 | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Vitality Scale | -5.30 Scores on a Scale | Standard Deviation 15.652 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Mental Health Scale | -0.28 Scores on a Scale | Standard Deviation 13.72 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Physical Functioning Scale | -4.05 Scores on a Scale | Standard Deviation 16.381 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Role Physical Scale | -1.75 Scores on a Scale | Standard Deviation 40.084 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Bodily Pain Scale | -1.13 Scores on a Scale | Standard Deviation 21.782 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | General Health Scale | -1.28 Scores on a Scale | Standard Deviation 15.824 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Vitality Scale | -4.05 Scores on a Scale | Standard Deviation 16.381 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Social Functioning Scale | -3.09 Scores on a Scale | Standard Deviation 28.908 |
| Placebo | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | Role Emotional Scale | 2.36 Scores on a Scale | Standard Deviation 45.984 |
Secondary
Mean Change From Baseline in CNS-LS Total Score by Visit
Center for Neurologic Studies-Lability Scale (CNS-LS) is an instrument for the measurement of PBA that has been validated for the use in patients with ALS and MS. It is a 7-item self-report questionnaire that measures the frequency and severity of PBA episodes, including assessments of labile laughter and labile tearfulness,and provides a score for total PBA (total score can range from 7-35). The following 5-point scoring was used: 1=Applies never, 2=Applies rarely, 3=Applies occasionally, 4=Applies frequently, 5=Applies most of the time. A score of 13 or higher may suggest PBA, and the higher the score the more severe the episodes.
Time frame: Baseline, Day 15, Day 29, Day 57, Day 84
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVP-923-30 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 15 (Visit2) | -6.77 Scores on a Scale | Standard Deviation 5.239 |
| AVP-923-30 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 29 (Visit 3) | -8.03 Scores on a Scale | Standard Deviation 5.591 |
| AVP-923-30 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 57 (Visit 4) | -8.59 Scores on a Scale | Standard Deviation 5.745 |
| AVP-923-30 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 84 (Visit 5) | -8.17 Scores on a Scale | Standard Deviation 6.104 |
| AVP-923-20 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 84 (Visit 5) | -8.24 Scores on a Scale | Standard Deviation 6.126 |
| AVP-923-20 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 15 (Visit2) | -6.27 Scores on a Scale | Standard Deviation 5.552 |
| AVP-923-20 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 57 (Visit 4) | -8.89 Scores on a Scale | Standard Deviation 5.501 |
| AVP-923-20 | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 29 (Visit 3) | -7.62 Scores on a Scale | Standard Deviation 5.421 |
| Placebo | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 84 (Visit 5) | -5.72 Scores on a Scale | Standard Deviation 5.28 |
| Placebo | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 29 (Visit 3) | -5.70 Scores on a Scale | Standard Deviation 5.034 |
| Placebo | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 57 (Visit 4) | -5.66 Scores on a Scale | Standard Deviation 5.038 |
| Placebo | Mean Change From Baseline in CNS-LS Total Score by Visit | Day 15 (Visit2) | -4.58 Scores on a Scale | Standard Deviation 4.982 |
Secondary
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)
The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Time frame: Baseline to Day 84
Population: Efficacy Evaluable (EE) Population - included all subjects who were protocol adherent, defined as those who completed the Day 84 visit or the end-of-study visit within 48 hours of a discontinuation, and who took as least 80% of their scheduled doses prior to discontinuation of the study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVP-923-30 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | Frequency Score | -1.68 Scores on a Scale | Standard Deviation 4.102 |
| AVP-923-30 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | Severity Score | -0.80 Scores on a Scale | Standard Deviation 3.109 |
| AVP-923-20 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | Frequency Score | -3.09 Scores on a Scale | Standard Deviation 6.241 |
| AVP-923-20 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | Severity Score | -1.81 Scores on a Scale | Standard Deviation 4.206 |
| Placebo | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | Frequency Score | -1.25 Scores on a Scale | Standard Deviation 4.86 |
| Placebo | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | Severity Score | -0.91 Scores on a Scale | Standard Deviation 4.026 |
Secondary
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)
The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Time frame: Baseline to Day 84
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVP-923-30 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | Frequency Score | -1.62 Scores on a Scale | Standard Deviation 4.11 |
| AVP-923-30 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | Severity Score | -0.74 Scores on a Scale | Standard Deviation 3.102 |
| AVP-923-20 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | Frequency Score | -2.56 Scores on a Scale | Standard Deviation 6.205 |
| AVP-923-20 | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | Severity Score | -1.59 Scores on a Scale | Standard Deviation 4.128 |
| Placebo | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | Frequency Score | -1.33 Scores on a Scale | Standard Deviation 4.837 |
| Placebo | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | Severity Score | -0.98 Scores on a Scale | Standard Deviation 4.008 |
Secondary
Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects
Subjects with MS were instructed to also record daily the pain they experienced using the PRS. After evaluating the subject's ability to comply with these requirements, the investigator determined if a caregiver should complete the study diary and assessments. Subjects rated their pain over the past 12 hours on a scale of 0 to 10 (0=none, 10=worst pain ever experienced).
Time frame: Baseline, Day 15, Day 29, Day 57, Day 84
Population: ITT Population - MS Subjects only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVP-923-30 | Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects | -1.0 Scores on a Scale | Standard Deviation 2.39 |
| AVP-923-20 | Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects | -0.7 Scores on a Scale | Standard Deviation 1.84 |
| Placebo | Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects | -0.4 Scores on a Scale | Standard Deviation 2.61 |