Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The objectives of the study are to evaluate the safety, tolerability, and efficacy of 3 doses of AVP-923 capsules in the treatment of central neuropathic pain in participants with multiple sclerosis.
The objectives of the study are to evaluate the safety, tolerability, and efficacy of 3 doses of AVP-923 (dextromethorphan [DM]/quinidine [Q]) capsules containing either 45 mg DM and 10 mg Q (AVP-923-45) or 30 mg DM and 10 mg Q (AVP-923-30) or 20 mg DM and 10 mg Q (AVP-923-20) compared to placebo, for the treatment of central neuropathic pain in a population of participants with multiple sclerosis (MS) over a 12-week period. The MS participant population enrolled includes participants with relapsing-remitting multiple sclerosis (RRMS) and participants with secondary progressive multiple sclerosis (SPMS).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| AVP-923-45 | Experimental |
| |
| AVP-923-30 | Experimental |
| |
| AVP-923-20 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AVP-923-45 | Drug | AVP-923-45 (dextromethorphan 45 mg/quinidine 10 mg) capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Association Between the Dextromethorphan Plasma Concentration and the Change From Baseline Pain Rating Scale (PRS) Score to the Average Pain Rating Scale Score During Days 57 Through 84 | PRS required participants to rate their pain over the past 12 hours (hrs) on a scale of 0 to 10 (0=no pain; 10=worst possible pain). Baseline (B) PRS was defined as the average of the PRS scores in the last 7 days collected prior to the B visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the B visit, then the average of up to 7 of the most recent PRS scores available prior to the B visit was used. Post-B PRS was the average of Days 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-B PRS scores was used. Change from B was calculated as the post-B score minus B score. The average logarithms of dextromethorphan plasma concentrations (Cmax) on Days 22 and 50 are reported in primary outcome measure #2 below. Pearson correlation was calculated between Cmax as one group of data across the reporting groups and Change from Baseline in PRS score. | Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations) |
| Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50 | The average of the logarithms of the DM plasma concentrations on Days 22 and 50 were presented. | 0 to 3 hours post-dose on Day 22 and 50 |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of the Adjusted Mean Change From Baseline PRS Score to the Average PRS Score During Days 57 Through 84 | The PRS required participants to rate their pain over the past 12 hours on a scale of 0 to 10 (0=no pain; 10=worst possible pain) by circling the number that best described their pain on average over the past 12 hours. Baseline PRS was defined as the average of the PRS scores in the last 7 days collected prior to the Baseline visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the Baseline visit, then the average of up to 7 of the most recent PRS scores available prior to the Baseline visit was used. Post-Baseline PRS was the average of the Day 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-Baseline PRS scores was used. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Modified Ashworth Scale (MAS) Scores | MAS is not considered as a true endpoint. MAS scores were assessed at Baseline only. Change from Baseline could not be calculated because data for the later timepoints was not collected. | Baseline; Day 85 |
Main Inclusion Criteria:
Multiple Sclerosis (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS]), Clinical history and symptoms of central neuropathic pain (dysesthetic pain) for at least 3 months prior to screening, pain rating scale (PRS) baseline score = or > 4, No MS relapse within previous 30 days.
Main Exclusion Criteria:
Personal history of complete heart block, QT interval corrected for heart rate (QTc) prolongation, or torsades de pointes, family history of congenital QT interval prolongation syndrome, Myasthenia Gravis, Beck Depression Inventory Second Edition (BDI-II) score > 19
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| North Central Neurology Associates PC | Cullman | Alabama | 35058 | United States | ||
| St. Joseph's Hospital Medical Center |
After screening procedures, participants underwent a 1-week washout period for all analgesic medications, with the exception of ibuprofen in doses that did not exceed 800 milligrams per day (mg/day).
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received one matching placebo capsule in the morning during the first 7 days of the study. Participants then received one matching placebo capsule twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| AVP-923-30 | Drug | AVP-923-30 (dextromethorphan 30 mg/quinidine 10 mg) capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment. |
|
| AVP-923-20 | Drug | AVP-923-20 (dextromethorphan 20 mg/quinidine 10 mg) capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment. |
|
|
| Placebo | Drug | Matching placebo capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment. |
|
| Baseline; Days 57 through 84 |
| Mean Change From Baseline in Fatigue Severity Scale (FSS) Scores at Days 57 Through 84 | The FSS questionnaire consisted of 9 statements that attempted to explore the severity of fatigue symptoms in participants with MS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus, and was designed to differentiate fatigue from clinical depression because both share some of the same symptoms. Participants were asked to respond to each statement on a scale of 1 to 7, with 1 indicating "Strongly Disagree" and 7 indicating "Strongly Agree." Total score ranging from 9 to 63, was computed as the sum of the sub-scores for all 9 statements; a higher score indicated increasing fatigue. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Post-Baseline FSS score was the average of Day 57 through 84 values. The analysis was carried out using an ANCOVA model, with the FSS change from Baseline to Days 85 as the dependent variable, | Baseline; Days 57 through 84 |
| Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85 | The EDSS, a method of quantifying disability in participants with MS was based on neurological examination of 8 functional systems (FS) (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other) that allowed neurologists to assign a FS score to each of these systems. Neurological findings in each FS were scored on a scale of 0 (low level of problems) to 5 (high level of problems). The "other" category was not rated numerically but measured disability related to a particular issue, like motor loss. A total averaged EDSS score was then calculated on a scale of 0 (normal) to 10 (death from MS). The total EDSS score was determined by 2 factors: gait and FS scores. A higher score indicated greater disability. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; Days 22 and 85 |
| Mean Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Scores at Day 85 | MSIS-29, an instrument measuring the physical (20 items) and psychological (9 items) impact of MS from the participants' perspective was used to evaluate therapeutic effectiveness from the participants' perspective. Participants were asked to circle the response that best described the impact of MS on daily life on a scale of 0 (not at all) to 5 (extremely). The total MSIS-29 score ranged from 0 to 145, was calculated as the sum of the sub-scores for all 29 questions, with lower scores indicating better quality of life. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSIS-29 score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSIS-29 as a covariate. | Baseline; Day 85 |
| Mean Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Scores at Day 85 | PSQI, a self-rated questionnaire was used to assess sleep quality and disturbances over a 1-month time interval. A total of 19 individual items generated 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component was scored from 0 (no difficulty) to 3 (severe difficulty). The sum of the scores for the 7 components yielded 1 global score (ranging from 0 to 21). Higher PSQI score indicated worse quality of sleep. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the PSQI change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline PQIS as a covariate. | Baseline; Day 85 |
| Mean Change From Baseline in MS Neuropsychological Screening Questionnaire (MSNQ) Scores at Day 85 | MSNQ, a self-reporting, 15-item questionnaire was used to screen for cognitive impairment in participants with MS. Participants (or their informants) scored each item on a scale from 0 (not at all) to 4 (often and greatly interferes with life). The total MSNQ score was calculated as the sum of the sub-scores for all 15 questions and thus ranged from 0 to 60. A higher score indicated greater impairment. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSNQ score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSNQ as a covariate. | Baseline; Day 85 |
| Mean Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Day 85 | BDI-II, a 21-item, self-reported instrument was used to assess the existence and severity of symptoms of depression. Each item corresponded to a symptom of depression and as scored on a 4-point scale, ranging from 0 to 3. Participants were asked to consider each statement as it related to the way they have felt for the past 2 weeks. Each of the 21 items were summed to give a single score for the BDI-II (ranging from 0 to 63). A total score of 0 to 13 indicated minimal depression, a score of 14 to 19 indicated mild depression, a score of 20 to 28 indicated moderate depression, and a score of 29 to 63 indicated severe depression. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the BDI-II change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline BDI-II as a covariate. | Baseline; Day 85 |
| Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85 | The SDMT assessed organic cerebral dysfunction in both children (8 years and older) and adults. The SDMT involved a simple substitution task that normal participants could easily perform. Using a reference key, the examinee had 90 seconds to pair specific numbers with given geometric figures. The SDMT score was the total correct response (not counting errors) in 90 seconds and ranged from 0 to 110. Lower scores indicated increased dysfunction. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the SDMT change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline SDMT as a covariate. | Baseline; Day 85 |
| Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85 | The NRS was an 11-point scale for participant self-reporting of pain. The overall scores ranged from 0 (no spasticity) to 10 (worst possible spasticity). Higher scores indicated increased aggression. | Days 22, 50, and 85 |
| Mean Overall Patient Global Impression of Change (PGIC) Scores at Day 85 | The PGIC was a standard, validated 7-point categorical scale. The participant was asked to assess the overall change in his or her central neuropathic pain symptoms since entry into the study on a scale of 0 to 7 (0=much better; 7=much worse). Higher scores indicated worsening. | Day 85 |
| Phoenix |
| Arizona |
| 85013 |
| United States |
| Alta Bates Summit Medical Center | Berkeley | California | 94705 | United States |
| University of California, Irvine | Orange | California | 92868 | United States |
| Coordinated Clinical Research | San Diego | California | 92103 | United States |
| University of California, San Francisco | San Francisco | California | 94158 | United States |
| University of Colorado | Aurora | Colorado | 80045 | United States |
| Neurology Associates, PA | Maitland | Florida | 32751 | United States |
| Collier Neurologic Specialists | Naples | Florida | 34102 | United States |
| Laszlo J. Mate, MD | North Palm Beach | Florida | 33408 | United States |
| Neurology Associates of Ormond Beach | Ormond Beach | Florida | 32174 | United States |
| Neurological Associates | Pompano Beach | Florida | 33060 | United States |
| Neurologique Foundation | Ponte Vedra Beach | Florida | 32082-4040 | United States |
| Suncoast Neuroscience Associates, Inc. | St. Petersburg | Florida | 33713 | United States |
| University of South Florida | Tampa | Florida | 33612 | United States |
| Geodyssey Research, LLC | Vero Beach | Florida | 32960 | United States |
| Shepard Center | Atlanta | Georgia | 30309 | United States |
| Rush-Presbyterian St. Luke's Medical Center | Chicago | Illinois | 60612 | United States |
| Consultants in Neurology | Northbrook | Illinois | 60062 | United States |
| Josephson Wallack Munshower Neurology, P.C. | Indianapolis | Indiana | 46256 | United States |
| MidAmerica Neuroscience Institute | Lenexa | Kansas | 66214 | United States |
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21287 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Michigan Neurology Associates, P.C. | Clinton Township | Michigan | 48035 | United States |
| Wayne State University | Detroit | Michigan | 48201 | United States |
| Henry Ford Health System | Detroit | Michigan | 48202 | United States |
| Advanced Neurology Specialists | Great Falls | Montana | 59405 | United States |
| Neurology Associates PC | Lincoln | Nebraska | 68506 | United States |
| Albany Medical Center Hospital | Albany | New York | 12208 | United States |
| NYU-Hospital for Joint Diseases | New York | New York | 10003 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| SUNY at Stony Brook | Stony Brook | New York | 11794 | United States |
| Carolinas Medical Center | Charlotte | North Carolina | 28207 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Oklahoma Medical Research Foundation | Oklahoma City | Oklahoma | 73104 | United States |
| Drexel University College of Medicine | Philadelphia | Pennsylvania | 19107 | United States |
| Geisinger Health System | Wilkes-Barre | Pennsylvania | 18711 | United States |
| Advanced Neurosciences Institute | Franklin | Tennessee | 37064 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Rocky Mountain MS Clinic | Salt Lake City | Utah | 84103 | United States |
| Neurological Associates | Henrico | Virginia | 23226 | United States |
| MS Center of Greater Washington | Vienna | Virginia | 22182 | United States |
| Swedish Medical Center | Seattle | Washington | 98122 | United States |
| MultiCare Health System | Tacoma | Washington | 98405 | United States |
| Instituto de Neurologia Cognitiva | Ciudad Autonoma de Buenos Aires | Buenos Aires | C1126AAB | Argentina |
| Hospital Britanico de Buenos Aires | Ciudad Autonoma de Buenos Aires | Buenos Aires | C1280AEB | Argentina |
| Hospital Italiano | Ciudad Autónoma de Buenos Aires | Buenos Aires | C1181ACH | Argentina |
| Instituto Argentino de Investigacion Neurologica | Ciudad de Buenos Aires | Buenos Aires | C1015ABR | Argentina |
| Hospital Churruca-Visca | Buenos Aires | C1437JCH | Argentina |
| Fundación Argentina Contra las Enfermedades Neurológicas del Envejecimiento - FACENE | Buenos Aires | CP1117ABD | Argentina |
| Medeos - Centro de Medicina Integral e Investigación Clínica | Buenos Aires | Argentina |
| Instituto de Neurología y Neurorrehabilitación del Litoral | Santa Fe | Argentina |
| Fakultni nemocnice u sv. Anny v Brne | Brno | Czechia |
| Fakultni nemocnice Hradec Kralove | Hradec Králové | 500 0 | Czechia |
| Nemocnice Jihlava, prispevkova organizace | Jihlava | 586 33 | Czechia |
| Fakultni Nemocnice Ostrava | Ostrava | 708 52 | Czechia |
| Vseobecna fakultni nemocnice v Praze | Prague | 128 21 | Czechia |
| Szpital Powiatowy w Czeladzi | Czeladź | 41-250 | Poland |
| Pomorskie Centrum Traumatologii im. M. Kopernika w Gdansku | Gdansk | 80-803 | Poland |
| Zespol Opieki Zdrowotnej w Konskich | Gmina Końskie | 26-200 | Poland |
| Diagnomed Clinical Research Sp. z.o.o. | Katowice | 40-594 | Poland |
| Niepubliczny Zaklad Opieki Zdrowotnej NEURO-MEDIC | Katowice | 40-752 | Poland |
| Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA | Katowice | Poland |
| Specjalistyczny Gabinet Neurologiczny | Plewiska | 62-064 | Poland |
| Niepubliczny Zaklad Opieki Zdrowotnej NEURO-KARD Ilkowski i Partnerzy Spolka Partnerska Lekarzy | Poznan | 61-289 | Poland |
| Osrodek Badan Klinicznych Indywidualnej Specjalistycznej Praktyki Lekarskiej | Szczecin | 70-215 | Poland |
| Hospital del Mar | Barcelona | Catalonia | 08003 | Spain |
| Hospital Vall D´Hebron | Barcelona | Catalonia | 08035 | Spain |
| Hospital Universitari de Girona Dr. Josep Trueta | Girona | Catalonia | 17007 | Spain |
| Hospital Universitario Virgen de la Arrixaca | El Palmar | Murcia | 30120 | Spain |
| Hospital Univ. Nuestra Sra. De La Candelaria | Santa Cruz de Tenerife | 38010 | Spain |
| Hospital Universitario Vírgen Macarena | Seville | 41009 | Spain |
| AVP-923-20 |
Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| FG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| FG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received one matching placebo capsule in the morning during the first 7 days of the study. Participants then received one matching placebo capsule twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| BG001 | AVP-923-20 | Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| BG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| BG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| BG004 | 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 |
| ||||||||||||||||
| Race/Ethnicity, Customized | 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 | Association Between the Dextromethorphan Plasma Concentration and the Change From Baseline Pain Rating Scale (PRS) Score to the Average Pain Rating Scale Score During Days 57 Through 84 | PRS required participants to rate their pain over the past 12 hours (hrs) on a scale of 0 to 10 (0=no pain; 10=worst possible pain). Baseline (B) PRS was defined as the average of the PRS scores in the last 7 days collected prior to the B visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the B visit, then the average of up to 7 of the most recent PRS scores available prior to the B visit was used. Post-B PRS was the average of Days 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-B PRS scores was used. Change from B was calculated as the post-B score minus B score. The average logarithms of dextromethorphan plasma concentrations (Cmax) on Days 22 and 50 are reported in primary outcome measure #2 below. Pearson correlation was calculated between Cmax as one group of data across the reporting groups and Change from Baseline in PRS score. | Modified Intention-To-Treat (MITT) Population: all participants in the ITT Population (randomized participants) who received at least one dose of study drug, provided a Baseline PRS score, and had at least one post-Baseline PRS assessment. Analysis was based on the randomized treatment assigned (regardless of actual treatment received). | Posted | Median | Full Range | units on a scale | Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations) |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50 | The average of the logarithms of the DM plasma concentrations on Days 22 and 50 were presented. | MITT Population. Only participants with available data were analyzed. | Posted | Median | Full Range | Log Micrograms per Liter | 0 to 3 hours post-dose on Day 22 and 50 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Comparison of the Adjusted Mean Change From Baseline PRS Score to the Average PRS Score During Days 57 Through 84 | The PRS required participants to rate their pain over the past 12 hours on a scale of 0 to 10 (0=no pain; 10=worst possible pain) by circling the number that best described their pain on average over the past 12 hours. Baseline PRS was defined as the average of the PRS scores in the last 7 days collected prior to the Baseline visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the Baseline visit, then the average of up to 7 of the most recent PRS scores available prior to the Baseline visit was used. Post-Baseline PRS was the average of the Day 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-Baseline PRS scores was used. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | MITT Population. Analysis was carried out using an analysis of covariance (ANCOVA) model, with the PRS score change from Baseline to Days 57-84 as the dependent variable, treatment group as a fixed effect, and the Baseline PRS score as a covariate. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Days 57 through 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in Fatigue Severity Scale (FSS) Scores at Days 57 Through 84 | The FSS questionnaire consisted of 9 statements that attempted to explore the severity of fatigue symptoms in participants with MS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus, and was designed to differentiate fatigue from clinical depression because both share some of the same symptoms. Participants were asked to respond to each statement on a scale of 1 to 7, with 1 indicating "Strongly Disagree" and 7 indicating "Strongly Agree." Total score ranging from 9 to 63, was computed as the sum of the sub-scores for all 9 statements; a higher score indicated increasing fatigue. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Post-Baseline FSS score was the average of Day 57 through 84 values. The analysis was carried out using an ANCOVA model, with the FSS change from Baseline to Days 85 as the dependent variable, | MITT Population. Only those participants with available data were analyzed. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Days 57 through 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85 | The EDSS, a method of quantifying disability in participants with MS was based on neurological examination of 8 functional systems (FS) (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other) that allowed neurologists to assign a FS score to each of these systems. Neurological findings in each FS were scored on a scale of 0 (low level of problems) to 5 (high level of problems). The "other" category was not rated numerically but measured disability related to a particular issue, like motor loss. A total averaged EDSS score was then calculated on a scale of 0 (normal) to 10 (death from MS). The total EDSS score was determined by 2 factors: gait and FS scores. A higher score indicated greater disability. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Safety Population: all participants who received at least 1 dose of study drug. Only participants with a value at both the Baseline visit and the specific post-Baseline visit have been included in the analysis. Safety analyses were performed on the safety population based on the treatment participants actually received. | Posted | Mean | Standard Deviation | units on a scale | Baseline; Days 22 and 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Scores at Day 85 | MSIS-29, an instrument measuring the physical (20 items) and psychological (9 items) impact of MS from the participants' perspective was used to evaluate therapeutic effectiveness from the participants' perspective. Participants were asked to circle the response that best described the impact of MS on daily life on a scale of 0 (not at all) to 5 (extremely). The total MSIS-29 score ranged from 0 to 145, was calculated as the sum of the sub-scores for all 29 questions, with lower scores indicating better quality of life. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSIS-29 score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSIS-29 as a covariate. | MITT Population | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Scores at Day 85 | PSQI, a self-rated questionnaire was used to assess sleep quality and disturbances over a 1-month time interval. A total of 19 individual items generated 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component was scored from 0 (no difficulty) to 3 (severe difficulty). The sum of the scores for the 7 components yielded 1 global score (ranging from 0 to 21). Higher PSQI score indicated worse quality of sleep. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the PSQI change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline PQIS as a covariate. | MITT Population. For participants with missing data at Day 85, the last available value has been used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in MS Neuropsychological Screening Questionnaire (MSNQ) Scores at Day 85 | MSNQ, a self-reporting, 15-item questionnaire was used to screen for cognitive impairment in participants with MS. Participants (or their informants) scored each item on a scale from 0 (not at all) to 4 (often and greatly interferes with life). The total MSNQ score was calculated as the sum of the sub-scores for all 15 questions and thus ranged from 0 to 60. A higher score indicated greater impairment. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSNQ score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSNQ as a covariate. | MITT Population. Only those participants with available data were analyzed. For participants with missing data at Day 85, the last available value has been used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Day 85 | BDI-II, a 21-item, self-reported instrument was used to assess the existence and severity of symptoms of depression. Each item corresponded to a symptom of depression and as scored on a 4-point scale, ranging from 0 to 3. Participants were asked to consider each statement as it related to the way they have felt for the past 2 weeks. Each of the 21 items were summed to give a single score for the BDI-II (ranging from 0 to 63). A total score of 0 to 13 indicated minimal depression, a score of 14 to 19 indicated mild depression, a score of 20 to 28 indicated moderate depression, and a score of 29 to 63 indicated severe depression. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the BDI-II change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline BDI-II as a covariate. | MITT Population. For participants with missing data at Day 85, the last available value has been used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85 | The SDMT assessed organic cerebral dysfunction in both children (8 years and older) and adults. The SDMT involved a simple substitution task that normal participants could easily perform. Using a reference key, the examinee had 90 seconds to pair specific numbers with given geometric figures. The SDMT score was the total correct response (not counting errors) in 90 seconds and ranged from 0 to 110. Lower scores indicated increased dysfunction. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the SDMT change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline SDMT as a covariate. | MITT Population. Only those participants with available data were analyzed. For participants with missing data at Day 85, the last available value has been used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85 | The NRS was an 11-point scale for participant self-reporting of pain. The overall scores ranged from 0 (no spasticity) to 10 (worst possible spasticity). Higher scores indicated increased aggression. | MITT Population. Only participants with a value at both the Baseline visit and the specific post-Baseline visit have been included in the analysis. For participants with missing data at Day 85, the last available value has been used. | Posted | Mean | Standard Deviation | units on a scale | Days 22, 50, and 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Overall Patient Global Impression of Change (PGIC) Scores at Day 85 | The PGIC was a standard, validated 7-point categorical scale. The participant was asked to assess the overall change in his or her central neuropathic pain symptoms since entry into the study on a scale of 0 to 7 (0=much better; 7=much worse). Higher scores indicated worsening. | MITT Population. Only those participants with available data were analyzed. For participants with missing data at Day 85, the last available value has been used. | Posted | Mean | Standard Deviation | units on a scale | Day 85 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline in Modified Ashworth Scale (MAS) Scores | MAS is not considered as a true endpoint. MAS scores were assessed at Baseline only. Change from Baseline could not be calculated because data for the later timepoints was not collected. | Not Posted | Baseline; Day 85 | Participants |
AEs were collected up to Week 12.
Treatment-emergent adverse events (AEs) were defined as those events with an onset that was anytime during the study and while on treatment, following the first dose of study drug on Day 1. AEs were reported for members of the Safety Population, comprising all participants who received at least one dose of the study drug. Safety analyses were performed based on the treatment participants actually received.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received one matching placebo capsule in the morning during the first 7 days of the study. Participants then received one matching placebo capsule twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. | 0 | 49 | 1 | 49 | 33 | 49 |
| EG001 | AVP-923-20 | Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. | 0 | 54 | 1 | 54 | 40 | 54 |
| EG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. | 0 | 53 | 1 | 53 | 43 | 53 |
| EG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. | 0 | 53 | 2 | 53 | 40 | 53 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDra 14.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Duodenitis | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDra 14.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Multiple sclerosis relapse | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Muscle spasticity | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Neuropathic pain | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Uhthoff's phenomenon | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDra 14.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDra 14.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDra 14.1 | Non-systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDra 14.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDra 14.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDra 14.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 14.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDra 14.1 | Non-systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 14.1 | Non-systematic Assessment |
|
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 less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Avanir Medical Information | Avanir Pharmaceuticals | 855-572-2722 | medinfo@avanir.com |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C507057 | dextromethorphan - quinidine combination |
Not provided
Not provided
Not provided
| Male |
|
| Black or African American |
|
| Asian |
|
| Hispanic or Latino |
|
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG004 | Total | All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study. |
|
|
| OG001 |
| AVP-923-20 |
Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG004 | AVP-923-20 and AVP-923-30 | Participants received either AVP-923-20 or AVP-923-30 in the morning during the first 7 days of the study. Participants then received one capsule of AVP-20 or AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG005 | AVP-923-30 and AVP-923-45 | Participants received either AVP-923-30 or AVP-923-45 in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 or AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG006 | All AVP-923 | All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45. |
|
|
|
| AVP-923-20 |
Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
|
|
|
| OG001 | AVP-923-20 | Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG004 | Total | All participants receiving placebo, AVP-923-20, AVP-923-30, or AVP-923-45. |
|
|
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
|
|
|
| AVP-923-20 |
Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
|
|
|
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
|
|
|
| AVP-923-20 |
Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
|
|
|
Participants received one capsule containing 20 milligrams (mg) dextromethorphan (DM) and 10 mg quinidine (Q) (AVP-923-20) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-20 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment.
| OG002 | AVP-923-30 | Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
|
|
|
Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG004 | Total | All participants receiving placebo, AVP-923-20, AVP-923-30, or AVP-923-45. |
|
|
|
Participants received one capsule containing 30 mg DM and 10 mg Q (AVP-923-30) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-30 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG003 | AVP-923-45 | Participants received one capsule containing 45 mg DM and 10 mg Q (AVP-923-45) in the morning during the first 7 days of the study. Participants then received one capsule of AVP-923-45 twice daily (approximately every 12 hours) during the remaining 11 weeks of the study to complete 12 weeks of treatment. |
| OG004 | Total | All participants receiving placebo, AVP-923-20, AVP-923-30, or AVP-923-45. |
|
|
|
|
|
|
|