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This is a multicenter, randomized, placebo-controlled study to evaluate AVP-786 for the treatment of neurobehavioral disinhibition including aggression, agitation, and irritability in participants with traumatic brain injury (TBI).
Eligible participants for this study must have a diagnosis of neurobehavioral disinhibition including aggression, agitation, and irritability that persists after brain injury.
This is a multicenter, randomized, placebo-controlled study, consisting of up to 12 weeks of treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Overall Study: Stage 1 Placebo/Stage 2 Placebo or Stage 1 Placebo/Stage 2 AVP-786 | Placebo Comparator | Participants received AVP-786 matching placebo capsules, orally, twice daily (BID) during Weeks 1 to 6 of the Stage 1 treatment period. After Week 6 participants were classified as responders or non-responders and were re-randomized to receive either placebo, orally, BID or AVP-786 in a dose escalation schedule to reach the target dose of AVP-786-42.63/4.9, orally, BID during Week 7 to Week 12 of Stage 1 treatment period. |
|
| Overall Study: Stage 1 AVP-786/Stage 2 AVP-786 | Experimental | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 12 of the treatment period. |
|
| Stage 1: Placebo | Placebo Comparator | Participants received AVP-786 matching placebo capsules, orally, BID during Weeks 1 to 6 of the Stage 1 treatment period. |
|
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Placebo Comparator | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if modified Clinical Global Impression of Severity [mCGI-S] score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Administered as capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Stage 1: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the Neuropsychiatric Inventory Clinician Rating Scale (NPI-C) Subscale of Aggression, Agitation, and Irritability/Lability (NPI-C-3) | NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These are collectively rated first by the informant/caregiver based on frequency (0-4);severity (0-3);informant/caregiver distress (0-5) & then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. NPI-C-3= aggression, agitation, & irritability/lability subscales. NPI-C agitation domain= sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain= sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain= sum of clinician impression severity scores for irritability/lability questions 1-12 (score=0-36). NPI-C-3 composite score ranges from 0-99. Higher score= increased severity. Least square (LS) mean was analyzed using mixed effects model repeated measures (MMRM) analysis. | Baseline to Week 6 |
| Stage 2: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the NPI-C Subscale of NPI-C-3 | NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These domains are collectively rated by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by participant based on frequency (0-4), which is integrated by clinician into (0-3) clinical impression severity rating. NPI-C-3=aggression, agitation, & irritability/lability subscales. NPI-C agitation domain=sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain=sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain=sum of clinician impression severity scores for irritability/lability questions 1-12 (score= 0-36). NPI-C-3 composite score ranges from 0-99. Higher score=increased severity. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. | Week 7 to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Aggression | The NPI-C was used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C aggression domain score is the sum of clinician impression severity scores for aggression questions 1-8, score ranges from 0-24, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed= number of participants with data available for analysis. Number analyzed= number of participants with data available for analysis at the specified time point. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tuscaloosa Veterans Affairs Medical Center | Tuscaloosa | Alabama | 35404 | United States | ||
| Absolute Clinical Research Site#207 |
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing
Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
Study was conducted in 2 Stages. Participants randomized to receive placebo in Stage 1 were re-randomized after Week 6 to receive either placebo or AVP-786 in Stage 2. As pre-specified in protocol, participants randomized to 'AVP-786' arm were not re-randomized after Week 6 and continued receiving AVP-786 in the same arm throughout 12 weeks of study. Study is presented in 3 stages: Overall Study, Stage 1 & Stage 2.
Participants took part in this study at 67 investigative sites in the United States from 30 May 2017 to 31 August 2022. A total of 467 participants were screened of which 168 participants were randomized to receive placebo or AVP-786.
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| ID | Title | Description |
|---|---|---|
| FG000 | Overall Study: Stage 1 Placebo/Stage 2 Placebo or Stage 1 Placebo/Stage 2 AVP-786 | Participants received AVP-786 matching placebo capsules, orally, twice daily (BID) during Weeks 1 to 6 of the Stage 1 treatment period. After Week 6 participants were classified as responders or non-responders and were re-randomized to receive either placebo, orally, BID or AVP-786 in a dose escalation schedule to reach the target dose of AVP-786-42.63/4.9, orally, BID during Week 7 to Week 12 of Stage 1 treatment period. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study (Baseline to Week 12) |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 23, 2020 | Sep 1, 2025 |
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|
| Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Experimental | Participants who received placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28- 28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28 -28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID during Weeks 9 to 12 of the Stage 2 treatment period. |
|
| Stage 1: Placebo Responders to Stage 2: Placebo | Placebo Comparator | Participants who were randomized to receive placebo in Stage 1 and were classified as responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
|
| Stage 1: Placebo Responders to Stage 2: AVP-786 | Experimental | Participants who received placebo in Stage 1 and were classified as responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28- 28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28 -28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID during Weeks 9 to 12 of the Stage 2 treatment period. |
|
| Stage 1: AVP-786 | Experimental | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
|
| AVP-786-28 | Drug | 28 mg of d6-DM and 4.9 mg of Q |
|
| AVP-786-42.63 | Drug | 42.63 mg of d6-DM and 4.9 mg of Q |
|
| Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
| Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Agitation | The NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0 to 4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C agitation domain score is the sum of clinician impression severity scores for agitation questions 1-13, score ranges from 0-39, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point. | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
| Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Irritability/Lability | NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0 to 4), which the clinician then integrates into a (0-3) clinical impression severity rating. NPI-C irritability/lability domain score=sum of clinician impression severity scores for irritability/lability questions 1-12, score ranges from 0-36, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point. | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
| Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Disinhibition | The NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C disinhibition domain score is the sum of clinical impression severity scores for disinhibition questions 1-16, score ranges from 0-48, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point. | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
| Stage 1 and Stage 2: Change From Baseline in Modified Clinical Global Impression of Severity (mCGI-S) Scale Scores | mCGI-S is 7-point (1-7) scale requiring clinician to rate severity of participant's neurobehavioral disinhibition including aggression, agitation and irritability after NPI-C interview, at time of assessment relative to clinician's past experience with participants having same diagnosis. Considering total clinical experience, participant is assessed on severity of illness at time of rating as:0: not assessed;1: normal, not at all ill;2: borderline ill;3: mildly ill;4: moderately ill;5: markedly ill;6: severely ill;7: among most extremely ill participants. Higher score=increased severity. Negative change from baseline=improvement.LS mean was analyzed using analysis of covariance (ANCOVA) model. Overall number analyzed=participants with data available for analysis. Number analyzed=participants with data available for analysis at specified time point. | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
| Stage 1 and Stage 2: Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores | The PGI-S is a single-question scale used to assess the severity of symptoms of neurobehavioral disinhibition including aggression, agitation, and irritability, on a 7-point scale, as 1: normal, not at all ill; 2: borderline ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; or 7: extremely ill. A higher score indicates worsening of the symptoms. Negative change from baseline indicates improvement. LS mean was analyzed using ANCOVA model. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point. | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
| Stage 1 and Stage 2: Modified Clinical Global Impression of Change (mCGI-C) Raw Scores | The mGCI-C is a scale that requires the clinician to rate the change of the participant's neurobehavioral disinhibition including aggression, agitation, and irritability at the time of assessment after the NPI-C interview, relative to the clinician's past experience with the participant's neurobehavioral disinhibition at admission. Considering total clinical experience, a participant is assessed for change of mental illness as: 0: not assessed; 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; 7: very much worse. A higher score represents worsening of symptoms. Negative change from baseline indicates improvement. | Stage 1: Week 6; Stage 2: Week 12 |
| Stage 1 and Stage 2: Patient Global Impression of Change (PGI-C) Raw Scores | The PGI-C is a 7-point (1-7) scale used to assess treatment response, and it is rated as: 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; 7: very much worse. A higher score indicates worsening of the symptoms. Negative change from baseline indicates improvement. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point. | Stage 1: Week 6; Stage 2: Week 12 |
| Phoenix |
| Arizona |
| 85051 |
| United States |
| Perseverance Research Center Site#152 | Scottsdale | Arizona | 85254 | United States |
| ATP Clinical Research Site#150 | Costa Mesa | California | 92626 | United States |
| Kaizen Brain Center #224 | La Jolla | California | 92037 | United States |
| Sunwise Clinical Research, LLC Site#216 | Lafayette | California | 94543 | United States |
| Torrance Clinical Research Institute Site#157 | Lomita | California | 90717 | United States |
| Tibor Rubin VA Medical Center, SCIRE Biomedical Research Institute | Long Beach | California | 90822 | United States |
| Asclepes Research Centers - Panorama City Site #208 | Panorama City | California | 91402 | United States |
| The Neurology Group | Pomona | California | 91767 | United States |
| Mountain Mind | Colorado Springs | Colorado | 80903 | United States |
| Mountain View Clinical Research, Inc. Site# 202 | Denver | Colorado | 80209 | United States |
| Medical Center of the Rockies | Loveland | Colorado | 80538 | United States |
| Connecticut Clinical Research | Cromwell | Connecticut | 06416 | United States |
| Bradenton Research Center, Inc | Bradenton | Florida | 34205 | United States |
| Healthcare Innovative Institute, LLC Site# 173 | Coral Springs | Florida | 33067 | United States |
| Science Connections, LLC Site#161 | Doral | Florida | 33166 | United States |
| Design Neuroscience Center, PL | Doral | Florida | 33172 | United States |
| Alphab Global Research Site#163 | Jupiter | Florida | 33458 | United States |
| Meridien Research | Maitland | Florida | 32751 | United States |
| Premier Clinical Research Institute, Inc. | Miami | Florida | 33122 | United States |
| Project 4 Research | Miami | Florida | 33125 | United States |
| Allied Biomedical Research Institute, Inc. Site#151 | Miami | Florida | 33155 | United States |
| Health Synergy Clinical Research | Okeechobee | Florida | 34972 | United States |
| Roskamp Institute Clinic, Inc. | Sarasota | Florida | 34243 | United States |
| USF Dept of Psychiatry and Behavioral Neurosciences Site# 214 | Tampa | Florida | 33613 | United States |
| Meridien Research Site# 108 | Tampa | Florida | 33634 | United States |
| Hawaii Pacific Neuroscience Site#184 | Honolulu | Hawaii | 96817 | United States |
| The University of Kentucky research foundation | Lexington | Kentucky | 40536 | United States |
| Baptist Health | Richmond | Kentucky | 40475 | United States |
| Sisu BHR Site#200 | Springfield | Massachusetts | 01103 | United States |
| Neurobehavioral Medicine Group #222 | Bloomfield Hills | Michigan | 48302 | United States |
| Millennium Psychiatric Associates, LLC | Creve Coeur | Missouri | 63141 | United States |
| Sharlin Health and Neurology | Ozark | Missouri | 65721 | United States |
| Clinical Research Professionals | St Louis | Missouri | 63141 | United States |
| JFK Johnson Rehabilitation Institute | Edison | New Jersey | 08820 | United States |
| The NeuroCognitive Insititute | Mount Arlington | New Jersey | 07856 | United States |
| New York University School of Medicine Site #122 | New York | New York | 10016 | United States |
| Atrium Health - Carolinas Rehabilitation - Charlotte Site #166 | Charlotte | North Carolina | 28203 | United States |
| New Hope Clinical Research Site#194 | Charlotte | North Carolina | 28211 | United States |
| Carolina Headache Institute | Durham | North Carolina | 27713 | United States |
| Salisbury VAMC | Salisbury | North Carolina | 28144 | United States |
| Valley Medical Research | Centerville | Ohio | 45459 | United States |
| Cincinnati VA Medical Center | Cincinnati | Ohio | 45220 | United States |
| North Star Medical Research, LLC Site#154 | Middleburg Heights | Ohio | 44130 | United States |
| IPS Research Site#196 | Oklahoma City | Oklahoma | 73106 | United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| WJB Dorn VA-Wm. Jennings Bryan Dorn VA Medical Center | Columbia | South Carolina | 29205 | United States |
| University of Texas Southwestern Medical Site#140 | Dallas | Texas | 75390 | United States |
| Polytrauma Rehabilitation Center S. Texas VA Health Care System Site# 146 | San Antonio | Texas | 78229 | United States |
| Cedar Clinical Research #221 | Draper | Utah | 84020 | United States |
| Virginia Commonwealth University #172 | Richmond | Virginia | 23298 | United States |
| Virginia Commonwealth University Site#172 | Richmond | Virginia | 23298 | United States |
| Salem Research Institute Site# 138 | Salem | Virginia | 24153 | United States |
| FG001 | Overall Study: Stage 1 AVP-786/Stage 2 AVP-786 | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 12 of the treatment period. |
| FG002 | Stage 1: Placebo | Participants received AVP-786 matching placebo capsules, orally, BID during Weeks 1 to 6 of the Stage 1 treatment period. |
| FG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if modified Clinical Global Impression of Severity [mCGI-S] score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| FG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who received placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28- 28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28 -28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID during Weeks 9 to 12 of the Stage 2 treatment period. |
| FG005 | Stage 1: Placebo Responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| FG006 | Stage 1: Placebo Responders to Stage 2: AVP-786 | Participants who received placebo in Stage 1 and were classified as responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28- 28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28 -28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID during Weeks 9 to 12 of the Stage 2 treatment period. |
| FG007 | Stage 1 and 2: AVP-786 | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. Participants who completed Stage 1, continued to receive AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
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| COMPLETED |
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| NOT COMPLETED |
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| Stage 1 (Baseline to Week 6) |
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| Stage 2 (Week 7 to Week 12) |
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Safety population included all participants who received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study: Placebo | Participants received AVP-786 matching placebo capsules, orally, BID during Weeks 1 to 6 of the Stage 1 treatment period. After Week 6 participants were classified as responders or non-responders and were re-randomized to receive either placebo, orally, BID or AVP-786 in a dose escalation schedule to reach the target dose of AVP-786-42.63/4.9, orally, BID during Week 7 to Week 12 of Stage 1 treatment period. |
| BG001 | Overall Study: AVP-786 | Participants received AVP-786-28/4.9 (d6-DM 28 mg/ Q 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 12 of the treatment period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Stage 1: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the Neuropsychiatric Inventory Clinician Rating Scale (NPI-C) Subscale of Aggression, Agitation, and Irritability/Lability (NPI-C-3) | NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These are collectively rated first by the informant/caregiver based on frequency (0-4);severity (0-3);informant/caregiver distress (0-5) & then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. NPI-C-3= aggression, agitation, & irritability/lability subscales. NPI-C agitation domain= sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain= sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain= sum of clinician impression severity scores for irritability/lability questions 1-12 (score=0-36). NPI-C-3 composite score ranges from 0-99. Higher score= increased severity. Least square (LS) mean was analyzed using mixed effects model repeated measures (MMRM) analysis. | Modified intent-to-treat (mITT) population. Stage 1: Participants randomized in Stage 1 who took at least 1 dose of study medication & had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1. Overall number analyzed=participants with data available for analysis. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline to Week 6 |
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| Primary | Stage 2: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the NPI-C Subscale of NPI-C-3 | NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These domains are collectively rated by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by participant based on frequency (0-4), which is integrated by clinician into (0-3) clinical impression severity rating. NPI-C-3=aggression, agitation, & irritability/lability subscales. NPI-C agitation domain=sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain=sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain=sum of clinician impression severity scores for irritability/lability questions 1-12 (score= 0-36). NPI-C-3 composite score ranges from 0-99. Higher score=increased severity. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. | mITT population. Stage 2: participants randomized into Stage 2 with at least 1 NPI-C-3 efficacy assessment in Stage 2. As pre-specified in protocol, data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Least Squares Mean | Standard Error | score on a scale | Week 7 to Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Aggression | The NPI-C was used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C aggression domain score is the sum of clinician impression severity scores for aggression questions 1-8, score ranges from 0-24, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed= number of participants with data available for analysis. Number analyzed= number of participants with data available for analysis at the specified time point. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Least Squares Mean | Standard Error | score on a scale | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Agitation | The NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0 to 4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C agitation domain score is the sum of clinician impression severity scores for agitation questions 1-13, score ranges from 0-39, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Least Squares Mean | Standard Error | score on a scale | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Irritability/Lability | NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0 to 4), which the clinician then integrates into a (0-3) clinical impression severity rating. NPI-C irritability/lability domain score=sum of clinician impression severity scores for irritability/lability questions 1-12, score ranges from 0-36, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Least Squares Mean | Standard Error | score on a scale | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Disinhibition | The NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) & informant/caregiver distress (0-5), then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C disinhibition domain score is the sum of clinical impression severity scores for disinhibition questions 1-16, score ranges from 0-48, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Least Squares Mean | Standard Error | score on a scale | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in Modified Clinical Global Impression of Severity (mCGI-S) Scale Scores | mCGI-S is 7-point (1-7) scale requiring clinician to rate severity of participant's neurobehavioral disinhibition including aggression, agitation and irritability after NPI-C interview, at time of assessment relative to clinician's past experience with participants having same diagnosis. Considering total clinical experience, participant is assessed on severity of illness at time of rating as:0: not assessed;1: normal, not at all ill;2: borderline ill;3: mildly ill;4: moderately ill;5: markedly ill;6: severely ill;7: among most extremely ill participants. Higher score=increased severity. Negative change from baseline=improvement.LS mean was analyzed using analysis of covariance (ANCOVA) model. Overall number analyzed=participants with data available for analysis. Number analyzed=participants with data available for analysis at specified time point. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Least Squares Mean | Standard Error | score on a scale | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores | The PGI-S is a single-question scale used to assess the severity of symptoms of neurobehavioral disinhibition including aggression, agitation, and irritability, on a 7-point scale, as 1: normal, not at all ill; 2: borderline ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; or 7: extremely ill. A higher score indicates worsening of the symptoms. Negative change from baseline indicates improvement. LS mean was analyzed using ANCOVA model. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Least Squares Mean | Standard Error | score on a scale | Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12 |
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| Secondary | Stage 1 and Stage 2: Modified Clinical Global Impression of Change (mCGI-C) Raw Scores | The mGCI-C is a scale that requires the clinician to rate the change of the participant's neurobehavioral disinhibition including aggression, agitation, and irritability at the time of assessment after the NPI-C interview, relative to the clinician's past experience with the participant's neurobehavioral disinhibition at admission. Considering total clinical experience, a participant is assessed for change of mental illness as: 0: not assessed; 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; 7: very much worse. A higher score represents worsening of symptoms. Negative change from baseline indicates improvement. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Mean | Standard Deviation | score on a scale | Stage 1: Week 6; Stage 2: Week 12 |
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| Secondary | Stage 1 and Stage 2: Patient Global Impression of Change (PGI-C) Raw Scores | The PGI-C is a 7-point (1-7) scale used to assess treatment response, and it is rated as: 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; 7: very much worse. A higher score indicates worsening of the symptoms. Negative change from baseline indicates improvement. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point. | mITT population. Stage 1:all participants randomized in Stage 1 who took at least 1 dose of study medication &had at least 1 post-baseline NPI-C-3 composite score efficacy assessment in Stage 1; Stage 2:participants randomized into Stage 2 &had at least 1 NPI-C-3 efficacy assessment in Stage 2(after Week 6). As pre-specified in protocol data for placebo non-responders re-randomized into Stage 2 was used to estimate & report Stage 2 efficacy. Hence only these Stage 2 arms are reported for the OM. | Posted | Mean | Standard Deviation | score on a scale | Stage 1: Week 6; Stage 2: Week 12 |
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From start of study up to 7 days after the last dose of study drug (up to 13 weeks)
Safety population- all participants who received at least one dose of study medication. As pre-specified in SAP, data was collected and reported by pooling the participants into one of the 2 arms based on the treatment received during the study (placebo / AVP-786). All Placebo arm includes participants who were treated with placebo in Stages 1, Stage 2, or both stages of the study. All AVP-786 arm includes participants who received AVP-786 throughout the study and only in Stage 2.
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 | All Placebo | Participants received AVP-786 matching placebo capsules, orally, BID, during Stage 1 or Stage 2 of the study treatment. | 0 | 83 | 0 | 83 | 4 | 83 |
| EG001 | All AVP-786 | Participants who were randomized to receive AVP-768 throughout the study and participants who were randomized to receive placebo in Stage 1 and were then re-randomized after Week 6 to receive AVP-786 in Stage 2. Participants received AVP-786-28/4.9 capsule along with AVP-786 matching placebo capsule, orally, QD for 1 week, followed by AVP-786-28/4.9 capsule, orally, BID, for the next one week and AVP-786-42.63/4.9 capsules (target dose), orally, BID during the rest of the treatment period. | 0 | 115 | 3 | 115 | 7 | 115 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Enterobacter sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Development | Otsuka Pharmaceutical Development & Commercialization, Inc. | 1-609-524-6788 | clinicaltransparency@otsuka-us.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 18, 2022 | Sep 1, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000374 | Aggression |
| D011595 | Psychomotor Agitation |
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D000096762 | Aberrant Motor Behavior in Dementia |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D012919 | Social Behavior |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D011596 | Psychomotor Disorders |
| D019954 | Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
Not provided
Not provided
| Lost to Follow-up |
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| Non-compliance With Study Drug |
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| Withdrawal by Subject |
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| Trial Site Terminated by Sponsor |
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| Reason Not Specified |
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| Physician Decision |
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| Lost to Follow-up |
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| Protocol Deviation |
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| Withdrawal by Subject |
|
| Reason Not Specified |
|
| Male |
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| Black or African American |
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| Asian |
|
| American Indian or Alaska Native |
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| Native Hawaiian or Other Pacific Islander |
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| Other |
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| Not Hispanic or Latino |
|
| OG001 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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| OG001 | Stage 1: AVP-786 | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
| OG002 | Stage 1: Placebo Non-responders; to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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| OG001 | Stage 1: AVP-786 | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
| OG002 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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| OG001 | Stage 1: AVP-786 | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
| OG002 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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| OG001 | Stage 1: AVP-786 | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
| OG002 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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| OG001 | Stage 1: AVP-786 | Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
| OG002 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
| OG002 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period. |
| OG002 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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| OG002 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID, during Weeks 9 to 12 of the Stage 2 treatment period. |
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