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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
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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
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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 
Overall Participants Analyzed 
[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
  Show All Outcome Measures

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

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

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 ]

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 ]

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 ]

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

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 ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
AVP-923-30 (Double-blind) 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-923-20 (Double-blind) 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.
Placebo (Double-blind) Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period.
AVP-923-30 (Open Label) Optional 12-week Open Label phase for subjects who completed 12-week DB phase.

Serious Adverse Events
    AVP-923-30 (Double-blind)   AVP-923-20 (Double-blind)   Placebo (Double-blind)   AVP-923-30 (Open Label)
Total, serious adverse events         
# participants affected / at risk   8/110 (7.27%)   9/107 (8.41%)   10/109 (9.17%)   14/253 (5.53%) 
Gastrointestinal disorders         
DYSPHAGIA † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   2/109 (1.83%)   1/253 (0.40%) 
STRIDOR † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
RESPIRATORY DISORDER † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
INGUINAL HERNIA † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
CONSTIPATION † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
ABDOMINAL PAIN † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
General disorders         
DISEASE PROGRESSION † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   1/109 (0.92%)   1/253 (0.40%) 
Hepatobiliary disorders         
CHOLELITHIASIS † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
CHOLECYSTITIS ACUTE † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
Infections and infestations         
UROSEPSIS † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
PNEUMONIA † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   0/253 (0.00%) 
INFECTION † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
CELLULITIS † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
CATHETER RELATED INFECTION † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
TOOTH INFECTION † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
SKIN INFECTION † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
POSTOPERATIVE WOUND INFECTION † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
APPENDICITIS † 1         
# participants affected / at risk   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         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   0/253 (0.00%) 
OVERDOSE † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
FEEDING TUBE COMPLICATION † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   1/253 (0.40%) 
COMPLICATION OF DEVICE INSERTION † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
RADIUS FRACTURE † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
HAND FRACTURE † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
FACIAL BONES FRACTURE † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
Investigations         
OXYGEN SATURATION DECREASED † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
CARDIAC ENZYMES INCREASED † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
Metabolism and nutrition disorders         
DEHYDRATION † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
HYPONATRAEMIA † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
Musculoskeletal and connective tissue disorders         
MUSCLE SPASMS † 1         
# participants affected / at risk   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         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
Nervous system disorders         
TRANSIENT ISCHAEMIC ATTACK † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
SYNCOPE † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   0/253 (0.00%) 
MUSCLE SPASTICITY † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
MULTIPLE SCLEROSIS † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   0/253 (0.00%) 
MULTIPLE SCLEROSIS RELAPSE † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   2/253 (0.79%) 
Psychiatric disorders         
SUICIDE ATTEMPT † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
ANXIETY † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   0/253 (0.00%) 
PSYCHOTIC DISORDER † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   0/109 (0.00%)   1/253 (0.40%) 
Respiratory, thoracic and mediastinal disorders         
RESPIRATORY FAILURE † 1         
# participants affected / at risk   3/110 (2.73%)   1/107 (0.93%)   1/109 (0.92%)   2/253 (0.79%) 
PULMONARY EMBOLISM † 1         
# participants affected / at risk   1/110 (0.91%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
DYSPNOEA † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   1/109 (0.92%)   1/253 (0.40%) 
RESPIRATORY DEPRESSION † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
PNEUMONIA ASPIRATION † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   1/109 (0.92%)   0/253 (0.00%) 
INCREASED BRONCHIAL SECRETION † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   0/253 (0.00%) 
BRONCHOSPASM † 1         
# participants affected / at risk   0/110 (0.00%)   1/107 (0.93%)   0/109 (0.00%)   0/253 (0.00%) 
ACUTE RESPIRATORY DISTRESS SYNDROME † 1         
# participants affected / at risk   1/110 (0.91%)   0/107 (0.00%)   0/109 (0.00%)   0/253 (0.00%) 
Vascular disorders         
DEEP VEIN THROMBOSIS † 1         
# participants affected / at risk   0/110 (0.00%)   0/107 (0.00%)   2/109 (1.83%)   0/253 (0.00%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 10.1




  Other Adverse Events


  Limitations and Caveats
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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
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