Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS (STAR)

This study has been completed.
Sponsor:
Collaborator:
INC Research
Information provided by (Responsible Party):
Avanir Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00573443
First received: December 13, 2007
Last updated: June 5, 2013
Last verified: June 2013
Results First Received: July 18, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Pseudobulbar Affect (PBA)
Interventions: Drug: dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg
Drug: dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects diagnosed with pseudobulbar affect (PBA) secondary to amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.
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.
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.

Participant Flow for 2 periods

Period 1:   Double-Blind Phase
    AVP-923-30     AVP-923-20     Placebo  
STARTED     110     107     109  
Subjects With PBA Secondary to ALS     65     68     64  
Subjects With PBA Secondary to MS     45     39     45  
COMPLETED     101     88     94  
NOT COMPLETED     9     19     15  
Lost to Follow-up                 1                 3                 2  
Exacerbation of MS symptoms                 1                 0                 1  
Adverse Event                 1                 5                 0  
Serious Adverse Event (AE)                 2                 3                 1  
Medication refusal due to AE                 2                 2                 0  
Withdrawal by Subject                 2                 2                 7  
Protocol Violation                 0                 2                 1  
Not specified                 0                 2                 3  

Period 2:   Open-Label Extension Phase
    AVP-923-30     AVP-923-20     Placebo  
STARTED     253 [1]   0 [2]   0 [2]
Subjects With PBA Secondary to ALS     146     0 [2]   0 [2]
Subjects With PBA Secondary to MS     107     0 [2]   0 [2]
COMPLETED     235     0 [2]   0 [2]
NOT COMPLETED     18     0     0  
Lost to Follow-up                 1                 0                 0  
Exacerbation of MS symptoms                 2                 0                 0  
Adverse Event                 3                 0                 0  
Serious Adverse Event                 5                 0                 0  
Withdrawal by Subject                 3                 0                 0  
Protocol Violation                 2                 0                 0  
Not Specified                 2                 0                 0  
[1] Subjects who completed any of the arms in the DB phase had the option to enroll in this OLE phase
[2] DB period of this arm could begin an optional 12 week OLE period taking AVP-923-30.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.
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.
Total Total of all reporting groups

Baseline Measures
    AVP-923-30     AVP-923-20     Placebo     Total  
Number of Participants  
[units: participants]
  110     107     109     326  
Age  
[units: Years]
Mean ± Standard Deviation
  53.08  ± 11.016     50.81  ± 11.114     50.27  ± 11.939     51.39  ± 11.356  
Gender  
[units: Participants]
       
Female     64     54     59     177  
Male     46     53     50     149  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   PBA Episode Rate Ratio (Post/Pre), Regression Adjusted   [ Time Frame: Baseline to Day 84 ]

Measure Type Primary
Measure Title PBA Episode Rate Ratio (Post/Pre), Regression Adjusted
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population - included all randomized subjects for the double-blind phase and all enrolled subjects for the open-label extension phase.

Reporting Groups
  Description
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.
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.
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.

Measured Values
    AVP-923-30     AVP-923-20     Placebo  
Number of Participants Analyzed  
[units: participants]
  110     107     109  
PBA Episode Rate Ratio (Post/Pre), Regression Adjusted  
[units: Unit-free (ratio of episodes/week)]
Least Squares Mean ( 95% Confidence Interval )
  0.247  
  ( 0.233 to 0.262 )  
  0.237  
  ( 0.224 to 0.251 )  
  0.465  
  ( 0.441 to 0.489 )  


Statistical Analysis 1 for PBA Episode Rate Ratio (Post/Pre), Regression Adjusted
Groups [1] AVP-923-30 vs. Placebo
Method [2] Regression, Longitudinal neg. binomial
P Value [3] <0.0001
Ratio of episode-rate reduction ratios [4] 0.5312
95% Confidence Interval ( 0.4939 to 0.5714 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for PBA Episode Rate Ratio (Post/Pre), Regression Adjusted
Groups [1] AVP-923-20 vs. Placebo
Method [2] Regression, Longitudinal neg. binomial
P Value [3] <0.0001
Ratio of episode-rate reduction ratios [4] 0.5103
95% Confidence Interval ( 0.4755 to 0.5477 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Mean Change From Baseline in CNS-LS Total Score by Visit   [ Time Frame: Baseline, Day 15, Day 29, Day 57, Day 84 ]

Measure Type Secondary
Measure Title Mean Change From Baseline in CNS-LS Total Score by Visit
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
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.
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.
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.

Measured Values
    AVP-923-30     AVP-923-20     Placebo  
Number of Participants Analyzed  
[units: participants]
  110     107     109  
Mean Change From Baseline in CNS-LS Total Score by Visit  
[units: Scores on a Scale]
Mean ± Standard Deviation
     
Day 15 (Visit2)     -6.77  ± 5.239     -6.27  ± 5.552     -4.58  ± 4.982  
Day 29 (Visit 3)     -8.03  ± 5.591     -7.62  ± 5.421     -5.70  ± 5.034  
Day 57 (Visit 4)     -8.59  ± 5.745     -8.89  ± 5.501     -5.66  ± 5.038  
Day 84 (Visit 5)     -8.17  ± 6.104     -8.24  ± 6.126     -5.72  ± 5.280  

No statistical analysis provided for Mean Change From Baseline in CNS-LS Total Score by Visit



3.  Secondary:   Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)   [ Time Frame: Baseline to Day 84 ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.
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.
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.

Measured Values
    AVP-923-30     AVP-923-20     Placebo  
Number of Participants Analyzed  
[units: participants]
  105     90     98  
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)  
[units: Scores on a Scale]
Mean ± Standard Deviation
     
Frequency Score     -1.68  ± 4.102     -3.09  ± 6.241     -1.25  ± 4.860  
Severity Score     -0.80  ± 3.109     -1.81  ± 4.206     -0.91  ± 4.026  

No statistical analysis provided for Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)



4.  Secondary:   Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)   [ Time Frame: Baseline to Day 84 ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
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.
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.
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.

Measured Values
    AVP-923-30     AVP-923-20     Placebo  
Number of Participants Analyzed  
[units: participants]
  110     107     109  
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)  
[units: Scores on a Scale]
Mean ± Standard Deviation
     
Frequency Score     -1.62  ± 4.110     -2.56  ± 6.205     -1.33  ± 4.837  
Severity Score     -0.74  ± 3.102     -1.59  ± 4.128     -0.98  ± 4.008  

No statistical analysis provided for Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)



5.  Secondary:   Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category   [ Time Frame: Baseline and Day 84 ]

Measure Type Secondary
Measure Title Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
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.
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.
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.

Measured Values
    AVP-923-30     AVP-923-20     Placebo  
Number of Participants Analyzed  
[units: participants]
  110     107     109  
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category  
[units: Scores on a Scale]
Mean ± Standard Deviation
     
Physical Functioning Scale     -0.90  ± 17.336     -5.30  ± 15.652     -4.05  ± 16.381  
Role Physical Scale     3.47  ± 36.747     -4.26  ± 39.764     -1.75  ± 40.084  
Bodily Pain Scale     4.09  ± 20.861     5.84  ± 20.437     -1.13  ± 21.782  
General Health Scale     -1.47  ± 17.273     -2.95  ± 16.266     -1.28  ± 15.824  
Vitality Scale     -0.90  ± 17.336     -5.30  ± 15.652     -4.05  ± 16.381  
Social Functioning Scale     9.34  ± 25.105     1.42  ± 28.577     -3.09  ± 28.908  
Role Emotional Scale     11.55  ± 47.711     -1.81  ± 45.924     2.36  ± 45.984  
Mental Health Scale     5.53  ± 17.067     3.09  ± 16.877     -0.28  ± 13.720  

No statistical analysis provided for Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category



6.  Secondary:   Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score   [ Time Frame: Baseline and Day 84 ]

Measure Type Secondary
Measure Title Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
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.
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.
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.

Measured Values
    AVP-923-30     AVP-923-20     Placebo  
Number of Participants Analyzed  
[units: participants]
  110     107     109  
Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score  
[units: Scores on a Scale]
Mean ± Standard Deviation
  -1.59  ± 5.294     -1.03  ± 5.183     -0.02  ± 6.320  

No statistical analysis provided for Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score



7.  Secondary:   Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects   [ Time Frame: Baseline, Day 15, Day 29, Day 57, Day 84 ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population - MS Subjects only

Reporting Groups
  Description
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.
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.
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.

Measured Values
    AVP-923-30     AVP-923-20     Placebo  
Number of Participants Analyzed  
[units: participants]
  45     39     45  
Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects  
[units: Scores on a Scale]
Mean ± Standard Deviation
  -1.0  ± 2.39     -0.7  ± 1.84     -0.4  ± 2.61  

No statistical analysis provided for Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information