Trial Outcomes & Findings for A Multicenter, Randomized, Double-blind, Placebo-controlled, 3-parallel-group Comparison Trial to Investigate the Effect of Nalmefene on Alcohol Consumption Reduction in Patients With Alcohol Dependence (Phase 3 Trial) (NCT NCT02364947)

NCT ID: NCT02364947

Last Updated: 2019-09-30

Results Overview

The number of HDDs is defined as the number of days per month \[days/month\] with alcohol consumption of \> 60 g for males and \> 40 g for females

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 678 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2019-09-30

Participant Flow

Safety analysis set, which included all randomized patients who received ≥1 dose of the study medication.

Participant milestones

Measure	Nalmefene Hydrochloride 20 mg as-needed, tablets, orally, 24 weeks	Nalmefene Hydrochloride 10 mg as-needed, tablets, orally, 24 weeks	Placebo as-needed, tablets, orally, 24 weeks
Overall Study STARTED	248	184	245
Overall Study COMPLETED	189	139	219
Overall Study NOT COMPLETED	59	45	26

Reasons for withdrawal

Measure	Nalmefene Hydrochloride 20 mg as-needed, tablets, orally, 24 weeks	Nalmefene Hydrochloride 10 mg as-needed, tablets, orally, 24 weeks	Placebo as-needed, tablets, orally, 24 weeks
Overall Study Withdrawal by Subject	10	8	9
Overall Study Adverse Event	45	33	11
Overall Study Protocol Violation	1	1	1
Overall Study Physician Decision	3	2	5
Overall Study Death	0	1	0

Baseline Characteristics

A Multicenter, Randomized, Double-blind, Placebo-controlled, 3-parallel-group Comparison Trial to Investigate the Effect of Nalmefene on Alcohol Consumption Reduction in Patients With Alcohol Dependence (Phase 3 Trial)

Baseline characteristics by cohort

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally	Total n=666 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	213 Participants n=5 Participants	159 Participants n=7 Participants	217 Participants n=5 Participants	589 Participants n=4 Participants
Age, Categorical >=65 years	29 Participants n=5 Participants	21 Participants n=7 Participants	27 Participants n=5 Participants	77 Participants n=4 Participants
Age, Continuous	48.9 years STANDARD_DEVIATION 12.2 • n=5 Participants	49.2 years STANDARD_DEVIATION 11.9 • n=7 Participants	48.1 years STANDARD_DEVIATION 11.4 • n=5 Participants	48.7 years STANDARD_DEVIATION 11.8 • n=4 Participants
Sex: Female, Male Female	72 Participants n=5 Participants	46 Participants n=7 Participants	90 Participants n=5 Participants	208 Participants n=4 Participants
Sex: Female, Male Male	170 Participants n=5 Participants	134 Participants n=7 Participants	154 Participants n=5 Participants	458 Participants n=4 Participants
Region of Enrollment Japan	242 participants n=5 Participants	180 participants n=7 Participants	244 participants n=5 Participants	666 participants n=4 Participants
Heavy Drinking Days (HDDs)	22.64 days/month STANDARD_DEVIATION 6.37 • n=5 Participants	23.49 days/month STANDARD_DEVIATION 6.07 • n=7 Participants	22.97 days/month STANDARD_DEVIATION 6.44 • n=5 Participants	22.99 days/month STANDARD_DEVIATION 6.32 • n=4 Participants
Total Alcohol Consumption (TAC)	93.07 g/day STANDARD_DEVIATION 37.45 • n=5 Participants	95.93 g/day STANDARD_DEVIATION 41.10 • n=7 Participants	95.08 g/day STANDARD_DEVIATION 48.70 • n=5 Participants	94.58 g/day STANDARD_DEVIATION 42.79 • n=4 Participants
Drinking Risk Level (DRL) Low	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Drinking Risk Level (DRL) Medium	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Drinking Risk Level (DRL) High	135 Participants n=5 Participants	93 Participants n=7 Participants	127 Participants n=5 Participants	355 Participants n=4 Participants
Drinking Risk Level (DRL) Very high	107 Participants n=5 Participants	87 Participants n=7 Participants	116 Participants n=5 Participants	310 Participants n=4 Participants
Clinical Global Impression - Severity of Illness (CGI-S) score	3.38 units on a scale STANDARD_DEVIATION 1.06 • n=5 Participants	3.48 units on a scale STANDARD_DEVIATION 1.15 • n=7 Participants	3.45 units on a scale STANDARD_DEVIATION 1.09 • n=5 Participants	3.43 units on a scale STANDARD_DEVIATION 1.09 • n=4 Participants
Serum gamma-glutamyltransferase (γ-GT)	84.7 IU/L STANDARD_DEVIATION 105.4 • n=5 Participants	80.7 IU/L STANDARD_DEVIATION 103.8 • n=7 Participants	70.7 IU/L STANDARD_DEVIATION 78.7 • n=5 Participants	78.5 IU/L STANDARD_DEVIATION 96.1 • n=4 Participants
Serum alanine aminotransferase (ALT)	24.3 IU/L STANDARD_DEVIATION 14.2 • n=5 Participants	24.5 IU/L STANDARD_DEVIATION 14.9 • n=7 Participants	23.3 IU/L STANDARD_DEVIATION 14.8 • n=5 Participants	24.0 IU/L STANDARD_DEVIATION 14.6 • n=4 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

The number of HDDs is defined as the number of days per month [days/month] with alcohol consumption of > 60 g for males and > 40 g for females

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 12	-12.25 days/month Standard Error 0.64	-12.09 days/month Standard Error 0.74	-7.91 days/month Standard Error 0.61

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 24	-13.25 days/month Standard Error 0.66	-13.88 days/month Standard Error 0.77	-9.33 days/month Standard Error 0.63

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in Total Alcohol Consumption (TAC) From Baseline at Week 12	-44.90 g/day Standard Error 2.01	-45.36 g/day Standard Error 2.32	-32.43 g/day Standard Error 1.91

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in Total Alcohol Consumption (TAC) From Baseline at Week 24	-49.43 g/day Standard Error 2.13	-49.55 g/day Standard Error 2.45	-38.28 g/day Standard Error 1.99

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with a downward shift in drinking risk level of two categories or more

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Response Shift Drinking Risk Level (RSDRL) at Week 12	41.3 percentage	35.7 percentage	20.1 percentage

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with a downward shift in drinking risk level of two categories or more

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Response Shift Drinking Risk Level (RSDRL) at Week 24	44.4 percentage	47.5 percentage	27.5 percentage

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with low or lower drinking risk level

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Response Low Drinking Risk Level (RLDRL) at Week 12	29.6 percentage	25.3 percentage	10.7 percentage

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with low or lower drinking risk level

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Response Low Drinking Risk Level (RLDRL) at Week 24	29.6 percentage	32.6 percentage	17.6 percentage

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with a 70% decrease in TAC

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
70% TAC Responder Rate at Week 12	18.0 percentage	19.5 percentage	8.5 percentage

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with a 70% decrease in TAC

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
70% TAC Responder Rate at Week 24	23.8 percentage	23.4 percentage	10.8 percentage

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with ≤4 HDDs

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
HDD Responder Rate at Week 12	35.0 percentage	36.4 percentage	19.2 percentage

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

Proportion of patients with ≤4 HDDs

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
HDD Responder Rate at Week 24	33.9 percentage	44.0 percentage	25.2 percentage

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

The CGI-S scale was used by clinicians when assessing their global impression of a patient's current clinical condition. The investigator or subinvestigator used his/her clinical experience with this patient population to rate the severity of a subject's clinical condition on a 7-point scale ranging from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients).

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in CGI-S From Baseline at Week 12	-0.60 units on a scale Standard Error 0.05	-0.63 units on a scale Standard Error 0.06	-0.34 units on a scale Standard Error 0.05

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

The CGI-S scale was used by clinicians when assessing their global impression of a patient's current clinical condition. The investigator or subinvestigator used his/her clinical experience with this patient population to rate the severity of a subject's clinical condition on a 7-point scale ranging from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients).

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in CGI-S From Baseline at Week 24	-0.75 units on a scale Standard Error 0.06	-0.77 units on a scale Standard Error 0.07	-0.41 units on a scale Standard Error 0.05

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

The CGI-I scale is used to assess a patient's improvement (or worsening). The investigator or subinvestigator assesses a subject's condition relative to baseline on a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse).

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in CGI-I From Baseline at Week 12	2.62 units on a scale Standard Error 0.07	2.65 units on a scale Standard Error 0.08	3.13 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

The CGI-I scale was used to assess a patient's improvement (or worsening). The investigator or subinvestigator assesses a subject's condition relative to baseline on a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse).

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in CGI-I From Baseline at Week 24	2.49 units on a scale Standard Error 0.07	2.44 units on a scale Standard Error 0.09	2.99 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

All-patients-randomised set

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 12	3.666 IU/L Standard Error 0.027	3.702 IU/L Standard Error 0.031	3.858 IU/L Standard Error 0.025

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

All-patients-randomised set

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 24	3.663 IU/L Standard Error 0.031	3.692 IU/L Standard Error 0.035	3.831 IU/L Standard Error 0.028

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

All-patients-randomised set

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 12	2.968 IU/L Standard Error 0.023	2.988 IU/L Standard Error 0.027	3.038 IU/L Standard Error 0.021

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.

All-patients-randomised set

Outcome measures

Measure	Nalmefene Hydrochloride 20 mg n=242 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=180 Participants Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=244 Participants Placebo: As-needed; tablets, orally
Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 24	2.971 IU/L Standard Error 0.023	2.987 IU/L Standard Error 0.027	3.036 IU/L Standard Error 0.021

Adverse Events

Nalmefene Hydrochloride 20 mg

Serious events: 2 serious events

Other events: 175 other events

Deaths: 0 deaths

Nalmefene Hydrochloride 10 mg

Serious events: 2 serious events

Other events: 125 other events

Deaths: 1 deaths

Placebo

Serious events: 2 serious events

Other events: 127 other events

Deaths: 0 deaths

Serious adverse events

Measure	Nalmefene Hydrochloride 20 mg n=248 participants at risk Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=184 participants at risk Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=245 participants at risk Placebo: As-needed; tablets, orally
Hepatobiliary disorders Chronic hepatitis	0.40% 1/248 • Number of events 1 • 24-week treatment period	0.00% 0/184 • 24-week treatment period	0.00% 0/245 • 24-week treatment period
Infections and infestations Gastroenteritis	0.40% 1/248 • Number of events 1 • 24-week treatment period	0.00% 0/184 • 24-week treatment period	0.00% 0/245 • 24-week treatment period
Injury, poisoning and procedural complications Anastomotic ulcer haemorrhage	0.00% 0/248 • 24-week treatment period	0.00% 0/184 • 24-week treatment period	0.41% 1/245 • Number of events 1 • 24-week treatment period
Injury, poisoning and procedural complications Femur fracture	0.00% 0/248 • 24-week treatment period	0.54% 1/184 • Number of events 1 • 24-week treatment period	0.00% 0/245 • 24-week treatment period
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/248 • 24-week treatment period	0.54% 1/184 • Number of events 1 • 24-week treatment period	0.00% 0/245 • 24-week treatment period
Psychiatric disorders Alcoholism	0.00% 0/248 • 24-week treatment period	0.00% 0/184 • 24-week treatment period	0.41% 1/245 • Number of events 1 • 24-week treatment period

Other adverse events

Measure	Nalmefene Hydrochloride 20 mg n=248 participants at risk Nalmefene hydrochloride: As-needed; tablets, orally	Nalmefene Hydrochloride 10 mg n=184 participants at risk Nalmefene hydrochloride: As-needed; tablets, orally	Placebo n=245 participants at risk Placebo: As-needed; tablets, orally
Cardiac disorders Palpitations	5.2% 13/248 • 24-week treatment period	3.8% 7/184 • 24-week treatment period	0.82% 2/245 • 24-week treatment period
Gastrointestinal disorders Constipation	5.2% 13/248 • 24-week treatment period	4.3% 8/184 • 24-week treatment period	0.82% 2/245 • 24-week treatment period
Gastrointestinal disorders Nausea	31.9% 79/248 • 24-week treatment period	31.5% 58/184 • 24-week treatment period	6.1% 15/245 • 24-week treatment period
Gastrointestinal disorders Vomiting	13.7% 34/248 • 24-week treatment period	8.7% 16/184 • 24-week treatment period	2.0% 5/245 • 24-week treatment period
General disorders Malaise	9.7% 24/248 • 24-week treatment period	3.8% 7/184 • 24-week treatment period	3.3% 8/245 • 24-week treatment period
Infections and infestations Nasopharyngitis	21.8% 54/248 • 24-week treatment period	21.7% 40/184 • 24-week treatment period	37.1% 91/245 • 24-week treatment period
Metabolism and nutrition disorders Decreased appetite	5.2% 13/248 • 24-week treatment period	6.0% 11/184 • 24-week treatment period	1.2% 3/245 • 24-week treatment period
Nervous system disorders Dizziness	20.6% 51/248 • 24-week treatment period	10.9% 20/184 • 24-week treatment period	4.1% 10/245 • 24-week treatment period
Nervous system disorders Headache	9.7% 24/248 • 24-week treatment period	11.4% 21/184 • 24-week treatment period	8.2% 20/245 • 24-week treatment period
Nervous system disorders Somnolence	15.7% 39/248 • 24-week treatment period	9.8% 18/184 • 24-week treatment period	6.9% 17/245 • 24-week treatment period
Psychiatric disorders Insomnia	8.1% 20/248 • 24-week treatment period	8.2% 15/184 • 24-week treatment period	0.82% 2/245 • 24-week treatment period

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., Ltd.

Email: CL_OPCJ_RDA_Team@otsuka.jp

Results disclosure agreements

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