Trial Outcomes & Findings for Safety and Efficacy of AVP-923 in the Treatment of Central Neuropathic Pain in Multiple Sclerosis (NCT NCT01324232)

Last Updated: 2021-11-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

209 participants

Primary outcome timeframe

Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations)

Results posted on

2021-11-22

Participant Flow

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).

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.
Overall Study STARTED	49	53	54	53
Overall Study COMPLETED	44	42	41	42
Overall Study NOT COMPLETED	5	11	13	11

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.	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.
Overall Study Protocol Violation	0	0	0	2
Overall Study Missing	0	0	1	0
Overall Study Participant's Personal Reason/Decision	0	1	0	0
Overall Study Lack of Efficacy	2	1	2	2
Overall Study Participant Refused Medication	0	1	0	0
Overall Study Intercurrent illness	0	0	0	1
Overall Study Adverse Event	2	5	6	6
Overall Study Withdrawal by Subject	0	3	4	0
Overall Study Lost to Follow-up	1	0	0	0

Baseline Characteristics

Safety and Efficacy of AVP-923 in the Treatment of Central Neuropathic Pain in Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=49 Participants 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.	AVP-923-20 n=53 Participants 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.	AVP-923-30 n=54 Participants 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.	AVP-923-45 n=53 Participants 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.	Total n=209 Participants Total of all reporting groups
Age, Continuous	49.7 years STANDARD_DEVIATION 8.41 • n=93 Participants	47.2 years STANDARD_DEVIATION 9.20 • n=4 Participants	49.1 years STANDARD_DEVIATION 11.21 • n=27 Participants	48.1 years STANDARD_DEVIATION 13.04 • n=483 Participants	48.5 years STANDARD_DEVIATION 10.63 • n=36 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	7 Participants n=4 Participants	12 Participants n=27 Participants	12 Participants n=483 Participants	40 Participants n=36 Participants
Sex: Female, Male Male	40 Participants n=93 Participants	46 Participants n=4 Participants	42 Participants n=27 Participants	41 Participants n=483 Participants	169 Participants n=36 Participants
Race/Ethnicity, Customized Caucasian	43 Participants n=93 Participants	46 Participants n=4 Participants	49 Participants n=27 Participants	48 Participants n=483 Participants	186 Participants n=36 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	4 Participants n=483 Participants	16 Participants n=36 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=93 Participants	3 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	6 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations)

Population: 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).

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total n=209 Participants All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=49 Participants 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.	AVP-923-20 n=53 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
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	-1.679 units on a scale Interval -6.79 to 2.0	-2.000 units on a scale Interval -7.86 to 5.71	-1.821 units on a scale Interval -7.86 to 2.06	-2.143 units on a scale Interval -7.6 to 5.71	-2.650 units on a scale Interval -6.54 to 3.0	—	—

PRIMARY outcome

Timeframe: 0 to 3 hours post-dose on Day 22 and 50

Population: MITT Population. Only participants with available data were analyzed.

The average of the logarithms of the DM plasma concentrations on Days 22 and 50 were presented.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=45 Participants 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.	Total n=133 Participants All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	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.	AVP-923-20 n=43 Participants 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.	AVP-923-30 n=45 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50	4.758 Log Micrograms per Liter Interval -1.61 to 5.81	4.394 Log Micrograms per Liter Interval -1.61 to 5.81	—	4.019 Log Micrograms per Liter Interval 2.38 to 4.84	4.493 Log Micrograms per Liter Interval 3.27 to 5.55	—	—

SECONDARY outcome

Timeframe: Baseline; Days 57 through 84

Population: 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.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total n=107 Participants All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=49 Participants 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.	AVP-923-20 n=53 Participants 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.	AVP-923-30 n=54 Participants 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.	AVP-923-30 and AVP-923-45 n=107 Participants 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.	All AVP-923 n=160 Participants All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Comparison of the Adjusted Mean Change From Baseline PRS Score to the Average PRS Score During Days 57 Through 84	-2.00 units on a scale Standard Error 0.319	-2.24 units on a scale Standard Error 0.224	-2.04 units on a scale Standard Error 0.332	-2.07 units on a scale Standard Error 0.319	-2.41 units on a scale Standard Error 0.316	-2.21 units on a scale Standard Error 0.225	-2.16 units on a scale Standard Error 0.184

SECONDARY outcome

Timeframe: Baseline; Days 57 through 84

Population: MITT Population. Only those participants with available data were analyzed.

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,

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=48 Participants 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.	AVP-923-20 n=52 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Change From Baseline in Fatigue Severity Scale (FSS) Scores at Days 57 Through 84	-2.12 units on a scale Standard Error 1.662	—	-3.32 units on a scale Standard Error 1.742	-2.00 units on a scale Standard Error 1.680	-6.32 units on a scale Standard Error 1.642	—	—

SECONDARY outcome

Timeframe: Baseline; Days 22 and 85

Population: 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.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total n=209 Participants All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=49 Participants 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.	AVP-923-20 n=54 Participants 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.	AVP-923-30 n=53 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85 Day 22	-0.0 units on a scale Standard Deviation 0.63	-0.1 units on a scale Standard Deviation 0.56	-0.1 units on a scale Standard Deviation 0.35	-0.1 units on a scale Standard Deviation 0.56	-0.2 units on a scale Standard Deviation 0.67	—	—
Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85 Day 85	0.0 units on a scale Standard Deviation 0.58	-0.1 units on a scale Standard Deviation 0.62	-0.1 units on a scale Standard Deviation 0.75	-0.1 units on a scale Standard Deviation 0.67	-0.1 units on a scale Standard Deviation 0.46	—	—

SECONDARY outcome

Timeframe: Baseline; Day 85

Population: MITT Population

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=49 Participants 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.	AVP-923-20 n=53 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Scores at Day 85	-1.41 units on a scale Standard Error 2.550	—	-4.84 units on a scale Standard Error 2.651	-4.34 units on a scale Standard Error 2.551	-6.50 units on a scale Standard Error 2.526	—	—

SECONDARY outcome

Timeframe: Baseline; Day 85

Population: MITT Population. For participants with missing data at Day 85, the last available value has been used.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=49 Participants 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.	AVP-923-20 n=53 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Scores at Day 85	-1.71 units on a scale Standard Error 0.472	—	-0.51 units on a scale Standard Error 0.490	-1.02 units on a scale Standard Error 0.471	-1.36 units on a scale Standard Error 0.467	—	—

SECONDARY outcome

Timeframe: Baseline; Day 85

Population: 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.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=48 Participants 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.	AVP-923-20 n=52 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Change From Baseline in MS Neuropsychological Screening Questionnaire (MSNQ) Scores at Day 85	0.47 units on a scale Standard Error 1.006	—	-0.99 units on a scale Standard Error 1.058	-1.48 units on a scale Standard Error 1.020	-1.88 units on a scale Standard Error 0.998	—	—

SECONDARY outcome

Timeframe: Baseline; Day 85

Population: MITT Population. For participants with missing data at Day 85, the last available value has been used.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=49 Participants 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.	AVP-923-20 n=53 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Day 85	1.15 units on a scale Standard Error 0.837	—	0.83 units on a scale Standard Error 0.868	-0.26 units on a scale Standard Error 0.835	0.21 units on a scale Standard Error 0.828	—	—

SECONDARY outcome

Timeframe: Baseline; Day 85

Population: 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.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=48 Participants 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.	AVP-923-20 n=52 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85 Total correct responses, Oral	2.06 units on a scale Standard Error 1.809	—	0.59 units on a scale Standard Error 2.045	2.96 units on a scale Standard Error 1.881	1.91 units on a scale Standard Error 1.525	—	—
Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85 Total correct responses, Written	0.20 units on a scale Standard Error 1.083	—	1.85 units on a scale Standard Error 1.111	3.62 units on a scale Standard Error 1.086	0.16 units on a scale Standard Error 1.158	—	—

SECONDARY outcome

Timeframe: Days 22, 50, and 85

Population: 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.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=53 Participants 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.	Total n=209 Participants All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=49 Participants 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.	AVP-923-20 n=53 Participants 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.	AVP-923-30 n=54 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85 Day 22	3.90 units on a scale Standard Deviation 2.649	3.54 units on a scale Standard Deviation 2.762	3.29 units on a scale Standard Deviation 2.717	3.56 units on a scale Standard Deviation 3.016	3.41 units on a scale Standard Deviation 2.723	—	—
Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85 Day 50	3.54 units on a scale Standard Deviation 2.364	3.42 units on a scale Standard Deviation 2.666	3.24 units on a scale Standard Deviation 2.721	2.89 units on a scale Standard Deviation 2.633	4.06 units on a scale Standard Deviation 2.888	—	—
Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85 Day 85	3.36 units on a scale Standard Deviation 2.666	3.50 units on a scale Standard Deviation 2.857	3.66 units on a scale Standard Deviation 2.869	3.13 units on a scale Standard Deviation 3.085	3.87 units on a scale Standard Deviation 2.825	—	—

SECONDARY outcome

Timeframe: Day 85

Population: 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.

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.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=45 Participants 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.	Total n=179 Participants All participants who received placebo, AVP-923-20, AVP-923-30, or AVP-923-45 treatments during the study.	Placebo n=43 Participants 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.	AVP-923-20 n=45 Participants 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.	AVP-923-30 n=46 Participants 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.	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.	All AVP-923 All participants receiving AVP-923-20, AVP-923-30, or AVP-923-45.
Mean Overall Patient Global Impression of Change (PGIC) Scores at Day 85	3.64 units on a scale Standard Deviation 2.298	3.84 units on a scale Standard Deviation 2.244	3.58 units on a scale Standard Deviation 1.842	4.42 units on a scale Standard Deviation 2.398	3.70 units on a scale Standard Deviation 2.346	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline; Day 85

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.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

AVP-923-20

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

AVP-923-30

Serious events: 1 serious events

Other events: 43 other events

Deaths: 0 deaths

AVP-923-45

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=49 participants at risk 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.	AVP-923-20 n=54 participants at risk 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.	AVP-923-30 n=53 participants at risk 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.	AVP-923-45 n=53 participants at risk 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.
Infections and infestations Cellulitis	0.00% 0/49 • 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.	1.9% 1/54 • 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.	0.00% 0/53 • 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.	0.00% 0/53 • 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.
Infections and infestations Pneumonia	0.00% 0/49 • 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.	0.00% 0/54 • 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.	1.9% 1/53 • 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.	0.00% 0/53 • 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.
Infections and infestations Tonsillitis	0.00% 0/49 • 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.	0.00% 0/54 • 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.	0.00% 0/53 • 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.	1.9% 1/53 • 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.
Ear and labyrinth disorders Vertigo	0.00% 0/49 • 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.	0.00% 0/54 • 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.	0.00% 0/53 • 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.	1.9% 1/53 • 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.
Eye disorders Diplopia	0.00% 0/49 • 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.	0.00% 0/54 • 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.	0.00% 0/53 • 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.	1.9% 1/53 • 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.
Gastrointestinal disorders Duodenitis	2.0% 1/49 • 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.	0.00% 0/54 • 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.	0.00% 0/53 • 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.	0.00% 0/53 • 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.

Other adverse events

Additional Information

Avanir Medical Information

Avanir Pharmaceuticals

Phone: 855-572-2722

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER