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| Name | Class |
|---|---|
| Syneos Health | OTHER |
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Objectives of the study are to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 (capsules containing either 30 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-30] or 20 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-20]) when compared to placebo, for the treatment of PBA in a population of patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) over a 12-week period. An additional objective is to determine the pharmacokinetic parameters of the two different doses of AVP-923 in a subset of the study population.
Pseudobulbar Affect (PBA) is a condition characterized by involuntary, sudden and frequent episodes of laughing and/or crying out of proportion or incongruous to the underlying emotion of happiness or sadness Other terms used to describe this condition include emotional lability, emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism, and pathological laughing and crying. The outbursts can occur spontaneously or in response to provocative stimuli such as questions or events.
A body of evidence suggests that PBA can be modulated through pharmacologic intervention.
Dextromethorphan (DM) is a low-affinity uncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, reducing the level of excitatory activity. DM also acts at the phencyclidine-binding site, which is part of the NMDA receptor complex. DM is a sigma receptor agonist, suppressing the release of excitatory neurotransmitters.
Quinidine (Q) is a known potent inhibitor of cytochrome P450 2D6 (CYP2D6), that decreases the metabolism of dextromethorphan and helps to achieve sustained and therapeutic levels of this drug.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DM 30 mg/Q 10 mg | Experimental | AVP-923-30/10 Capsules (30 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks |
|
| DM 20 mg/ Q 10 mg | Experimental | AVP-923-20/10 Capsules (20 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks |
|
| Placebo | Placebo Comparator | Placebo Capsules once daily for 1 week and then twice daily for an additional 11 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg | Drug | Dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) capsules (AVP-923 capsules), containing DM 20 mg/ Q 10 mg, taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period |
| Measure | Description | Time Frame |
|---|---|---|
| PBA Episode Rate Ratio (Post/Pre), Regression Adjusted | 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. | Baseline to Day 84 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in CNS-LS Total Score by Visit | 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. |
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Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Adrian Hepner, M.D. | Avanir Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Joseph's Hospital and Medical Center | Phoenix | Arizona | 85013 | United States | ||
| Neuromuscular Research Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20839238 | Result | Pioro EP, Brooks BR, Cummings J, Schiffer R, Thisted RA, Wynn D, Hepner A, Kaye R; Safety, Tolerability, and Efficacy Results Trial of AVP-923 in PBA Investigators. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol. 2010 Nov;68(5):693-702. doi: 10.1002/ana.22093. |
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Subjects diagnosed with pseudobulbar affect (PBA) secondary to amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-Blind Phase |
|
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|
|
| dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg | Drug | Dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) capsules (AVP-923 capsules), containing DM 30 mg/ Q 10 mg taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period |
|
|
| Placebo | Drug | Placebo capsules (identical in appearance to AVP-923 capsules being studied in this trial), taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period |
|
| Baseline, Day 15, Day 29, Day 57, Day 84 |
| Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | 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). | Baseline to Day 84 |
| Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | 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). | Baseline to Day 84 |
| Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | 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. | Baseline and Day 84 |
| Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score | 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. | Baseline and Day 84 |
| Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects | 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). | Baseline, Day 15, Day 29, Day 57, Day 84 |
| Scottsdale |
| Arizona |
| 85258 |
| United States |
| South Coast Clinical Trials | Anaheim | California | 92804 | United States |
| UCI Medical Center | Irvine | California | 92868 | United States |
| Center for Neurologic Study | La Jolla | California | 92103 | United States |
| UCLA School of Medicine | Los Angeles | California | 90095 | United States |
| The Forbes Norris MDA/ALS Research Center - California Pacific Medical Center | San Francisco | California | 94115 | United States |
| The ALS Center at UCSF | San Francisco | California | 94117 | United States |
| University of Colorado at Denver & Health Science Center | Aurora | Colorado | 80045 | United States |
| Neuroscience Center | Fort Lauderdale | Florida | 33334 | United States |
| Mayo Clinic | Jacksonville | Florida | 32224 | United States |
| University of Miami | Miami | Florida | 33136 | United States |
| Suncoast Neuroscience Associates | St. Petersburg | Florida | 33701 | United States |
| The ALS Center at Emory University | Atlanta | Georgia | 30322 | United States |
| Neurology Specialists of Decatur of Decatur | Decatur | Georgia | 30033 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Consultants in Neurology | Northbrook | Illinois | 60062 | United States |
| University of Kentucky Health Care - Dept. of Neurology | Lexington | Kentucky | 40536 | United States |
| The John Hopkins Universitiy | Baltimore | Maryland | 21287 | United States |
| Massachusets General Hospital | Boston | Massachusetts | 02129 | United States |
| Baystate Medical Center | Springfield | Massachusetts | 01199 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| St.Louis University - Neuromuscular Clinic | St Louis | Missouri | 63110 | United States |
| Advanced Neurology Specialists | Great Falls | Montana | 59405 | United States |
| Neurology Associates | Lincoln | Nebraska | 68506 | United States |
| Universitiy of Nevada | Las Vegas | Nevada | 89102 | United States |
| Upstate Clinical Research | Albany | New York | 12205 | United States |
| Jacobs Neurological Institute | Buffalo | New York | 14203 | United States |
| Mount Sinai Medical Center | New York | New York | 10029 | United States |
| Neurological Institute - Columbia Presbyterian Center | New York | New York | 10032 | United States |
| Carolinas Medical Center | Charlotte | North Carolina | 28207 | United States |
| Duke Universitiy Medical Center | Durham | North Carolina | 27710 | United States |
| Department of Neurology - The Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Ohio State Universitiy | Columbus | Ohio | 43210 | United States |
| Oregon Health Science University | Portland | Oregon | 97239 | United States |
| Drexel University - Department of Neurology | Philadelphia | Pennsylvania | 19107 | United States |
| The ALS Center - Penn Neurological Institute - The University of Pennsylvania | Philadelphia | Pennsylvania | 19107 | United States |
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| The Methodist Hospital - Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Department of Neuropsychiatry - Texas Tech University | Lubbock | Texas | 79430 | United States |
| University of Texas Health Science Center | San Antonio | Texas | 78229 | United States |
| Universitiy of Vermont | Burlington | Vermont | 05405 | United States |
| West Virginia University | Morgantown | West Virginia | 26506 | United States |
| Dean Foundation | Madison | Wisconsin | 53715 | United States |
| FACENE | Buenos Aires | Buenos Aires F.D. | 1117ABD | Argentina |
| IADIN | Buenos Aires | Buenos Aires F.D. | C1055AAD | Argentina |
| Hospital Italiano | Buenos Aires | Buenos Aires F.D. | C1181ACH | Argentina |
| INEBA | Buenos Aires | Buenos Aires F.D. | C1192AAW | Argentina |
| Hospital Ramos Mejia | Buenos Aires | Buenos Aires F.D. | C1221ADC | Argentina |
| Hospital Britanico | Buenos Aires | Buenos Aires F.D. | C1280AEB | Argentina |
| Policlinico Bancario | Buenos Aires | Buenos Aires F.D. | C1416DRJ | Argentina |
| FLENI | Buenos Aires | Buenos Aires F.D. | C1428AQK | Argentina |
| Hospital Militar Regional de Cordoba | Córdoba | Córdoba Province | X5000HGX | Argentina |
| Instituto Medico Rodriguez Alfici | Godoy Cruz | Mendoza Province | M5501AAP | Argentina |
| Instituto de Neurociencias Rosario | Rosario | Santa Fe Province | 2002KQJ | Argentina |
| Santa Casa de Misericordia de Belo Horizonte | Belo Horizonte | M G | 30.150-221 | Brazil |
| Hospital de Clínicas-UFPR | Curitiba | Paraná | 80.060.900 | Brazil |
| Hospital da Restauração | Recife | Pernambuco | 52.010-040 | Brazil |
| Hospital Universitário Clementino Fraga Filho | Rio de Janeiro | Rio de Janeiro | 21941-913 | Brazil |
| Hospital Moinhos de Vento | Porto Alegre | Rio Grande do Sul | 90.560.030 | Brazil |
| Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo | São Paulo | São Paulo | 05.403-000 | Brazil |
| FG001 | 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. |
| FG002 | 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. |
| Subjects With PBA Secondary to ALS |
|
| Subjects With PBA Secondary to MS |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Open-Label Extension Phase |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | PBA Episode Rate Ratio (Post/Pre), Regression Adjusted | 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. | Intent-to-Treat (ITT) population - included all randomized subjects for the double-blind phase and all enrolled subjects for the open-label extension phase. | Posted | Jul 2011 | Least Squares Mean | 95% Confidence Interval | Unit-free (ratio of episodes/week) | Baseline to Day 84 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in CNS-LS Total Score by Visit | 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. | ITT Population | Posted | Jul 2011 | Mean | Standard Deviation | Scores on a Scale | Baseline, Day 15, Day 29, Day 57, Day 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population) | 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). | 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. | Posted | Mean | Standard Deviation | Scores on a Scale | Baseline to Day 84 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population) | 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). | ITT Population | Posted | Mean | Standard Deviation | Scores on a Scale | Baseline to Day 84 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category | 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. | ITT Population | Posted | Mean | Standard Deviation | Scores on a Scale | Baseline and Day 84 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score | 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. | ITT Population | Posted | Mean | Standard Deviation | Scores on a Scale | Baseline and Day 84 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects | 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). | ITT Population - MS Subjects only | Posted | Mean | Standard Deviation | Scores on a Scale | Baseline, Day 15, Day 29, Day 57, Day 84 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 8 | 110 | 66 | 110 | ||
| EG001 | 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. | 9 | 107 | 65 | 107 | ||
| EG002 | 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. | 10 | 109 | 63 | 109 | ||
| EG003 | AVP-923-30 (Open Label) | Optional 12-week Open Label phase for subjects who completed 12-week DB phase. | 14 | 253 | 123 | 253 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| PULMONARY EMBOLISM | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| RESPIRATORY DEPRESSION | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| PNEUMONIA ASPIRATION | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| INCREASED BRONCHIAL SECRETION | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| BRONCHOSPASM | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| ACUTE RESPIRATORY DISTRESS SYNDROME | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| DYSPHAGIA | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| STRIDOR | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| RESPIRATORY DISORDER | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| INGUINAL HERNIA | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| CONSTIPATION | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| TRANSIENT ISCHAEMIC ATTACK | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| SYNCOPE | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| MUSCLE SPASTICITY | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| MULTIPLE SCLEROSIS | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| MULTIPLE SCLEROSIS RELAPSE | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| UROSEPSIS | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| PNEUMONIA | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| INFECTION | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| CELLULITIS | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| CATHETER RELATED INFECTION | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| TOOTH INFECTION | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| SKIN INFECTION | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| POSTOPERATIVE WOUND INFECTION | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| APPENDICITIS | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| POSTOPERATIVE RESPIRATORY DISTRESS | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| OVERDOSE | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| FEEDING TUBE COMPLICATION | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| COMPLICATION OF DEVICE INSERTION | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| RADIUS FRACTURE | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| HAND FRACTURE | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| FACIAL BONES FRACTURE | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| DEEP VEIN THROMBOSIS | Vascular disorders | MedDRA 10.1 | Systematic Assessment |
| |
| SUICIDE ATTEMPT | Psychiatric disorders | MedDRA 10.1 | Systematic Assessment |
| |
| ANXIETY | Psychiatric disorders | MedDRA 10.1 | Systematic Assessment |
| |
| PSYCHOTIC DISORDER | Psychiatric disorders | MedDRA 10.1 | Systematic Assessment |
| |
| OXYGEN SATURATION DECREASED | Investigations | MedDRA 10.1 | Systematic Assessment |
| |
| CARDIAC ENZYMES INCREASED | Investigations | MedDRA 10.1 | Systematic Assessment |
| |
| CHOLELITHIASIS | Hepatobiliary disorders | MedDRA 10.1 | Systematic Assessment |
| |
| CHOLECYSTITIS ACUTE | Hepatobiliary disorders | MedDRA 10.1 | Systematic Assessment |
| |
| DISEASE PROGRESSION | General disorders | MedDRA 10.1 | Systematic Assessment |
| |
| BREAST CANCER | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.1 | Systematic Assessment |
| |
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
| |
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
| |
| HYPONATRAEMIA | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NAUSEA | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| DIARRHOEA | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
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| DYSPHAGIA | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
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| DRY MOUTH | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
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| FATIGUE | General disorders | MedDRA 10.1 | Systematic Assessment |
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| NASOPHARYNGITIS | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
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| URINARY TRACT INFECTION | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
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| FALL | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
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| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
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| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
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| MUSCULAR WEAKNESS | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
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| SOMNOLENCE | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
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| DEPRESSION | Psychiatric disorders | MedDRA 10.1 | Systematic Assessment |
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Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nadine Knowles; Executive Director, Research & Development Operations | Avanir Pharmaceuticals | 1-949-268-8972 | nknowles@avanir.com |
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D003915 | Dextromethorphan |
| D011802 | Quinidine |
| C507057 | dextromethorphan - quinidine combination |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D002930 | Cinchona Alkaloids |
| D011812 | Quinuclidines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
Not provided
Not provided
| Adverse Event |
|
| Serious Adverse Event |
|
| Withdrawal by Subject |
|
| Protocol Violation |
|
| Other |
|
| Male |
|
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. |
| Regression, Longitudinal neg. binomial |
| <0.0001 |
| Ratio of episode-rate reduction ratios |
| 0.5103 |
| 2-Sided |
| 95 |
| 0.4755 |
| 0.5477 |
| Superiority or Other |
| OG002 | 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. |
|
|
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. |
| OG002 | 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. |
|
|
| OG002 | 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. |
|
|
| OG002 | 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. |
|
|
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. |
|
|
| OG002 |
| 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. |
|
|