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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 ]
  Hide Outcome Measure 4

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 
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 ]

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


  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
No text entered.


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Joao Siffert, MD, SVP R&D
Organization: Avanir Pharmaceuticals
phone: 949-268-1174
e-mail: jsiffert@avanir.com


Publications of Results:

Responsible Party: Avanir Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00573443     History of Changes
Other Study ID Numbers: 07-AVR-123
Study First Received: December 13, 2007
Results First Received: July 18, 2011
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Argentina: Human Research Bioethics Committee
Brazil: Ministry of Health
Brazil: National Committee of Ethics in Research