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

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ClinicalTrials.gov Identifier: NCT00573443
Recruitment Status : Completed
First Posted : December 14, 2007
Results First Posted : July 10, 2013
Last Update Posted : April 12, 2017
Sponsor:
Collaborator:
INC Research
Information provided by (Responsible Party):
Avanir Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, 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
Enrollment 326

Recruitment Details Subjects diagnosed with pseudobulbar affect (PBA) secondary to amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).
Pre-assignment Details  
Arm/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description 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 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. 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.
Period Title: Double-Blind Phase
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
Reason Not Completed
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 Title: Open-Label Extension Phase
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
Reason Not Completed
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.
Arm/Group Title AVP-923-30 AVP-923-20 Placebo Total
Hide Arm/Group Description 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 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. 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 of all reporting groups
Overall Number of Baseline Participants 110 107 109 326
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 110 participants 107 participants 109 participants 326 participants
53.08  (11.016) 50.81  (11.114) 50.27  (11.939) 51.39  (11.356)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 110 participants 107 participants 109 participants 326 participants
Female
64
  58.2%
54
  50.5%
59
  54.1%
177
  54.3%
Male
46
  41.8%
53
  49.5%
50
  45.9%
149
  45.7%
1.Primary Outcome
Title PBA Episode Rate Ratio (Post/Pre), Regression Adjusted
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 110 107 109
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit-free (ratio of episodes/week)
0.247
(0.233 to 0.262)
0.237
(0.224 to 0.251)
0.465
(0.441 to 0.489)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AVP-923-30, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Longitudinal neg. binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of episode-rate reduction ratios
Estimated Value 0.5312
Confidence Interval (2-Sided) 95%
0.4939 to 0.5714
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AVP-923-20, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Longitudinal neg. binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of episode-rate reduction ratios
Estimated Value 0.5103
Confidence Interval (2-Sided) 95%
0.4755 to 0.5477
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline in CNS-LS Total Score by Visit
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 110 107 109
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
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)
3.Secondary Outcome
Title Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 105 90 98
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
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)
4.Secondary Outcome
Title Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 110 107 109
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
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)
5.Secondary Outcome
Title Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 110 107 109
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
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)
6.Secondary Outcome
Title Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 110 107 109
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
-1.59  (5.294) -1.03  (5.183) -0.02  (6.320)
7.Secondary Outcome
Title Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population - MS Subjects only
Arm/Group Title AVP-923-30 AVP-923-20 Placebo
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 45 39 45
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
-1.0  (2.39) -0.7  (1.84) -0.4  (2.61)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AVP-923-30 (Double-blind) AVP-923-20 (Double-blind) Placebo (Double-blind) AVP-923-30 (Open Label)
Hide Arm/Group Description 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. 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. Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Optional 12-week Open Label phase for subjects who completed 12-week DB phase.
All-Cause Mortality
AVP-923-30 (Double-blind) AVP-923-20 (Double-blind) Placebo (Double-blind) AVP-923-30 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AVP-923-30 (Double-blind) AVP-923-20 (Double-blind) Placebo (Double-blind) AVP-923-30 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/110 (7.27%)   9/107 (8.41%)   10/109 (9.17%)   14/253 (5.53%) 
Gastrointestinal disorders         
DYSPHAGIA  1  1/110 (0.91%)  0/107 (0.00%)  2/109 (1.83%)  1/253 (0.40%) 
STRIDOR  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
RESPIRATORY DISORDER  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
INGUINAL HERNIA  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
CONSTIPATION  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
ABDOMINAL PAIN  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
General disorders         
DISEASE PROGRESSION  1  0/110 (0.00%)  1/107 (0.93%)  1/109 (0.92%)  1/253 (0.40%) 
Hepatobiliary disorders         
CHOLELITHIASIS  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
CHOLECYSTITIS ACUTE  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
Infections and infestations         
UROSEPSIS  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
PNEUMONIA  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  0/253 (0.00%) 
INFECTION  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
CELLULITIS  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
CATHETER RELATED INFECTION  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
TOOTH INFECTION  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
SKIN INFECTION  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
POSTOPERATIVE WOUND INFECTION  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
APPENDICITIS  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
Injury, poisoning and procedural complications         
POSTOPERATIVE RESPIRATORY DISTRESS  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  0/253 (0.00%) 
OVERDOSE  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
FEEDING TUBE COMPLICATION  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  1/253 (0.40%) 
COMPLICATION OF DEVICE INSERTION  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
RADIUS FRACTURE  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
HAND FRACTURE  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
FACIAL BONES FRACTURE  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
Investigations         
OXYGEN SATURATION DECREASED  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
CARDIAC ENZYMES INCREASED  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
Metabolism and nutrition disorders         
DEHYDRATION  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
HYPONATRAEMIA  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
Musculoskeletal and connective tissue disorders         
MUSCLE SPASMS  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
BREAST CANCER  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
Nervous system disorders         
TRANSIENT ISCHAEMIC ATTACK  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
SYNCOPE  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  0/253 (0.00%) 
MUSCLE SPASTICITY  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
MULTIPLE SCLEROSIS  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  0/253 (0.00%) 
MULTIPLE SCLEROSIS RELAPSE  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  2/253 (0.79%) 
Psychiatric disorders         
SUICIDE ATTEMPT  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
ANXIETY  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  0/253 (0.00%) 
PSYCHOTIC DISORDER  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  1/253 (0.40%) 
Respiratory, thoracic and mediastinal disorders         
RESPIRATORY FAILURE  1  3/110 (2.73%)  1/107 (0.93%)  1/109 (0.92%)  2/253 (0.79%) 
PULMONARY EMBOLISM  1  1/110 (0.91%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
DYSPNOEA  1  1/110 (0.91%)  0/107 (0.00%)  1/109 (0.92%)  1/253 (0.40%) 
RESPIRATORY DEPRESSION  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
PNEUMONIA ASPIRATION  1  0/110 (0.00%)  0/107 (0.00%)  1/109 (0.92%)  0/253 (0.00%) 
INCREASED BRONCHIAL SECRETION  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  0/253 (0.00%) 
BRONCHOSPASM  1  0/110 (0.00%)  1/107 (0.93%)  0/109 (0.00%)  0/253 (0.00%) 
ACUTE RESPIRATORY DISTRESS SYNDROME  1  1/110 (0.91%)  0/107 (0.00%)  0/109 (0.00%)  0/253 (0.00%) 
Vascular disorders         
DEEP VEIN THROMBOSIS  1  0/110 (0.00%)  0/107 (0.00%)  2/109 (1.83%)  0/253 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AVP-923-30 (Double-blind) AVP-923-20 (Double-blind) Placebo (Double-blind) AVP-923-30 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/110 (60.00%)   65/107 (60.75%)   63/109 (57.80%)   123/253 (48.62%) 
Gastrointestinal disorders         
NAUSEA  1  14/110 (12.73%)  8/107 (7.48%)  10/109 (9.17%)  15/253 (5.93%) 
DIARRHOEA  1  11/110 (10.00%)  14/107 (13.08%)  7/109 (6.42%)  0/253 (0.00%) 
CONSTIPATION  1  7/110 (6.36%)  6/107 (5.61%)  9/109 (8.26%)  17/253 (6.72%) 
DYSPHAGIA  1  4/110 (3.64%)  6/107 (5.61%)  2/109 (1.83%)  0/253 (0.00%) 
DRY MOUTH  1  7/110 (6.36%)  2/107 (1.87%)  0/109 (0.00%)  0/253 (0.00%) 
General disorders         
FATIGUE  1  9/110 (8.18%)  11/107 (10.28%)  10/109 (9.17%)  30/253 (11.86%) 
Infections and infestations         
NASOPHARYNGITIS  1  9/110 (8.18%)  6/107 (5.61%)  8/109 (7.34%)  14/253 (5.53%) 
URINARY TRACT INFECTION  1  8/110 (7.27%)  4/107 (3.74%)  3/109 (2.75%)  19/253 (7.51%) 
Injury, poisoning and procedural complications         
FALL  1  22/110 (20.00%)  14/107 (13.08%)  22/109 (20.18%)  40/253 (15.81%) 
Musculoskeletal and connective tissue disorders         
MUSCLE SPASMS  1  7/110 (6.36%)  3/107 (2.80%)  10/109 (9.17%)  0/253 (0.00%) 
PAIN IN EXTREMITY  1  5/110 (4.55%)  2/107 (1.87%)  8/109 (7.34%)  14/253 (5.53%) 
MUSCULAR WEAKNESS  1  6/110 (5.45%)  5/107 (4.67%)  4/109 (3.67%)  17/253 (6.72%) 
BACK PAIN  1  0/110 (0.00%)  0/107 (0.00%)  0/109 (0.00%)  16/253 (6.32%) 
Nervous system disorders         
HEADACHE  1  15/110 (13.64%)  15/107 (14.02%)  17/109 (15.60%)  27/253 (10.67%) 
DIZZINESS  1  20/110 (18.18%)  11/107 (10.28%)  6/109 (5.50%)  17/253 (6.72%) 
SOMNOLENCE  1  11/110 (10.00%)  9/107 (8.41%)  10/109 (9.17%)  16/253 (6.32%) 
Psychiatric disorders         
DEPRESSION  1  0/110 (0.00%)  1/107 (0.93%)  6/109 (5.50%)  0/253 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Nadine Knowles; Executive Director, Research & Development Operations
Organization: Avanir Pharmaceuticals
Phone: 1-949-268-8972
Responsible Party: Avanir Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00573443     History of Changes
Other Study ID Numbers: 07-AVR-123
First Submitted: December 13, 2007
First Posted: December 14, 2007
Results First Submitted: July 18, 2011
Results First Posted: July 10, 2013
Last Update Posted: April 12, 2017