Trial Outcomes & Findings for Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Intermittent Explosive Disorder (NCT NCT03420222)
NCT ID: NCT03420222
Last Updated: 2022-05-24
Results Overview
The OAS-M is a clinical-administered instrument designed to assess various manifestations of aggressive behavior through 2 domains: aggression and irritability. The OAS-M aggression domain includes 4 items: verbal assault, assault against objects, assault against others, and assault against self. The rater determines the frequency of each response (item) during the past week, and the frequency of each item is multiplied by the severity level (0 to 5), producing a raw score. This raw score is multiplied by severity weight for that item (verbal assault x 1, assault against objects x 2, assault against others x 3, and assault against self x 3). Each response is scored using a 6-point scale (0 = no events to 5 = most severe form of assault within that category). The weighted individual item scores are added to obtain the OAS-M Total Aggression score. Higher scores indicate increased aggression.
TERMINATED
PHASE2
10 participants
Baseline; Week 12
2022-05-24
Participant Flow
A total of 37 participants were screened; 27 participants were screen failures, and 10 were randomized to treatment.
Participant milestones
| Measure |
AVP-786
Participants received AVP-786-28 (deudextromethorphan hydrobromide \[d6-DM\] 28 milligrams \[mg\]/quinidine sulfate \[Q\] 4.9 mg) once daily (OD) for the first 7 days, followed by AVP-786-28 twice daily (BID) for the next 7 days. Beginning on Day 15, participants received AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) BID for 10 weeks.
|
Placebo
Participants received placebo BID for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
2
|
|
Overall Study
COMPLETED
|
3
|
1
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
Reasons for withdrawal
| Measure |
AVP-786
Participants received AVP-786-28 (deudextromethorphan hydrobromide \[d6-DM\] 28 milligrams \[mg\]/quinidine sulfate \[Q\] 4.9 mg) once daily (OD) for the first 7 days, followed by AVP-786-28 twice daily (BID) for the next 7 days. Beginning on Day 15, participants received AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) BID for 10 weeks.
|
Placebo
Participants received placebo BID for 12 weeks.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Intermittent Explosive Disorder
Baseline characteristics by cohort
| Measure |
AVP-786
n=8 Participants
Participants received AVP-786-28 (deudextromethorphan hydrobromide \[d6-DM\] 28 milligrams \[mg\]/quinidine sulfate \[Q\] 4.9 mg) once daily (OD) for the first 7 days, followed by AVP-786-28 twice daily (BID) for the next 7 days. Beginning on Day 15, participants received AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) BID for 10 weeks.
|
Placebo
n=2 Participants
Participants received placebo BID for 12 weeks.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
NA years
STANDARD_DEVIATION NA • n=5 Participants
|
NA years
STANDARD_DEVIATION NA • n=7 Participants
|
NA years
STANDARD_DEVIATION NA • n=5 Participants
|
|
Sex: Female, Male
Female
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
NA Participants
n=5 Participants
|
NA Participants
n=7 Participants
|
NA Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The OAS-M is a clinical-administered instrument designed to assess various manifestations of aggressive behavior through 2 domains: aggression and irritability. The OAS-M aggression domain includes 4 items: verbal assault, assault against objects, assault against others, and assault against self. The rater determines the frequency of each response (item) during the past week, and the frequency of each item is multiplied by the severity level (0 to 5), producing a raw score. This raw score is multiplied by severity weight for that item (verbal assault x 1, assault against objects x 2, assault against others x 3, and assault against self x 3). Each response is scored using a 6-point scale (0 = no events to 5 = most severe form of assault within that category). The weighted individual item scores are added to obtain the OAS-M Total Aggression score. Higher scores indicate increased aggression.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The OAS-M is a clinical-administered instrument designed to assess various manifestations of aggressive behavior through 2 domains: aggression, and irritability. The OAS-M irritability domain includes 2 global assessment items: global subjective irritability and global overt irritability. Each response is scored using a 6-point scale (0 = not at all to 5 = extreme). The 2 scores are added to create the OAS-M Total Irritability score (range = 0 to 10). Higher scores indicate increased irritability.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The OAS-M is a clinical-administered instrument designed to assess various manifestations of aggressive behavior through 2 domains: aggression and irritability. The OAS-M aggression domain includes 4 items: verbal assault, assault against objects, assault against others, and assault against self. The rater determines the frequency of each response (item) during the past week, and the frequency of each item is multiplied by the severity level (0 to 5), producing a raw score. This raw score is multiplied by severity weight for that item (verbal assault x 1, assault against objects x 2, assault against others x3, and assault against self x 3). Each response is scored using a 6-point scale (0 = no events to 5 = most severe form of assault). Higher scores indicate increased aggression.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The OAS-M is a clinical-administered instrument designed to assess various manifestations of aggressive behavior through 2 domains: aggression and irritability. The OAS-M irritability domain includes 2 items: global subjective irritability and global overt irritability. Each response is scored using a 6-point scale (0 = not at all; 5 = extreme). Higher scores indicate increased irritability.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The IED episodes were to be documented by the participants each evening before bedtime.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The IED episodes were to be documented by the participants each evening before bedtime and reviewed by the Investigator post dose.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned..
The IED episodes were to be documented by the participants each evening before bedtime. If the participant indicated that he/she experienced an IED episode, he/she was to document the number of episodes.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The IED episodes were to be documented by the participants each evening before bedtime. If the participant indicated that he/she experienced an IED episode, he/she was to document the number of episodes and to rate the severity of the worst episode (0 = not severe at all to 10 = worst severity imaginable).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The IED episodes were to be documented by the participants each evening before bedtime. If the participant indicated that he/she experienced an IED episode, he/she was to document the number of episodes and to rate the severity of distress experienced by the episode(s) (0 = no distress to 10 = worst distress imaginable).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The OAS-M is a clinical-administered instrument designed to assess various manifestations of aggressive behavior through 2 domains: aggression, and irritability. The OAS-M includes information regarding the number of Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) A1 aggressive episodes, and the number of DSM-5 A2 aggressive episodes experienced by the participants during the past week. The number of discrete IED episodes is calculated after an interview with the participant. Episodes identified as discrete are separated by at least 30 minutes; episodes separated by less than 30 minutes are considered a single episode.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The mCGI-S is a modified version of the CGI-S scale that provides a global evaluation of the participant's IED symptoms (e.g., aggression, anger, and irritability). The mCGI-S scale measures the severity of the participant's symptoms from the clinician's perspective in the context of other participants with IED. The mCGI-S responses are scored on a 7- point scale (1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The mCGI-C is a modified version of the CGI-C scale. The clinician rates the overall global change in the participant's IED symptoms (e.g., aggression, anger, and irritability) from Baseline at the scheduled double- blind visits. The mCGI-C responses are scored using a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The mPGI-S is a single-question scale. Participants rate the overall global severity of their IED symptoms (e.g., aggression, anger, and irritability) using a 7-point scale (1 = normal, no symptoms; 2 = borderline symptoms; 3 = mild symptoms; 4 = moderately bad symptoms; 5 = markedly bad symptoms; 6 = severely bad symptoms; 7 = extremely bad symptoms).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The mPGI-C is a single-question scale. Participants rate the overall global change in their IED symptoms (e.g., aggression, anger, and irritability) from Baseline at the scheduled double-blind visits. The mPGI- C responses are scored using a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The SDS is a 3-item, participant-rated questionnaire used to evaluate impairments in the domains of work/school, social life or leisure activities, and family life or home responsibility. Participants rate the degree of impairment in work/school, social life or leisure activities, and family life or home responsibility as a result of IED symptoms using a visual analogue scale (0 = no impairment; 1, 2, 3 = mildly; 4, 5, 6 = moderately; 7, 8, 9 = markedly; 10 = extremely). Only those score categories with at least one participant with event are reported.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The SF-12 is a 12-item, participant self-rated questionnaire used to measure the general health status and quality of life. The SF-12 includes questions to measure the effects of health on physical functioning, role limitations due to physical health, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems, and mental health. Scores range from 0 to 100. Higher scores indicate better health status.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline; Week 12Population: As the study was terminated early due to a business decision, with lack of enrollment, the data for this outcome measure was not collected or analyzed as planned.
The STAXI-2 is a 57-item, participant self-rated scale used to measure the intensity of anger as an emotional state (state anger) and the disposition to experience angry feelings as a personality trait (trait anger). The STAXI-2 includes a measure of state anger, trait anger, anger expression-out, anger expression-in, anger control-out and anger control, and the anger expression index (an overall measure of the expression and control of anger). The state anger items are scored using a 4-point scale (1 = not at all to 4 = very much so) to assess the intensity of anger feelings at a particular moment. The other scales are scored using a 4- point scale to assess how frequently angry feelings are experienced, expressed, suppressed, or controlled (1 = almost never to 4 = almost always).
Outcome measures
Outcome data not reported
Adverse Events
AVP-786
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AVP-786
n=8 participants at risk
Participants received AVP-786-28 (deudextromethorphan hydrobromide \[d6-DM\] 28 milligrams \[mg\]/quinidine sulfate \[Q\] 4.9 mg) once daily (OD) for the first 7 days, followed by AVP-786-28 twice daily (BID) for the next 7 days. Beginning on Day 15, participants received AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) BID for 10 weeks.
|
Placebo
n=2 participants at risk
Participants received placebo BID for 12 weeks.
|
|---|---|---|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
50.0%
1/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
50.0%
1/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Nervous system disorders
Dizziness
|
12.5%
1/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
0.00%
0/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Investigations
Electrocardiogram ST segment elevation
|
0.00%
0/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
50.0%
1/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Investigations
Haematocrit decreased
|
0.00%
0/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
50.0%
1/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
50.0%
1/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
0.00%
0/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
50.0%
1/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Psychiatric disorders
Nervousness
|
12.5%
1/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
0.00%
0/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Psychiatric disorders
Restlessness
|
12.5%
1/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
0.00%
0/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Infections and infestations
Urinary tract infection
|
12.5%
1/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
0.00%
0/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/8 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
50.0%
1/2 • Up to Day 85
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred after the first dose of the study drug through 30 days after the last dose. TEAEs are reported for all participants who received study medication. Participants were included in the treatment group based on the actual treatment received.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60