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
  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
  Hide Serious Adverse Events

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
  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
  Hide More Information

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