Trial Outcomes & Findings for Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 and Aripiprazole for Treatment of Acute Schizophrenia (NCT NCT00905307)

Last Updated: 2015-10-20

Results Overview

The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS total score is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

459 participants

Primary outcome timeframe

Baseline to Week 6

Results posted on

2015-10-20

Participant Flow

459 participants recruited at 74 study centres in the United States, Asia and Europe. Participants not responding adequately to treatment at Week 4 visit could continue in study and receive open-label OPC-34712 (starting dose 2.5 mg/day with option for decrease to 2 mg/day or increase to 3 mg/day) until Week 6 at study physician's discretion.

Partipants were randomized in a 1:2:2:2:2:1 ratio to the following groups: OPC-34712 0.25 mg arm, OPC-34712 low-dose, OPC-34712 mid-dose, OPC-34712 high-dose, Placebo, Aripiprazole. All other prohibited medications were discontinued at least 24 hours before the first dose of double-blind study medication.

Participant milestones

Participant milestones
Measure	OPC-34712 0.25 mg 0.25 mg once daily (QD) for 6 weeks	OPC-34712 Low-dose 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 Mid-dose 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 High Dose 5.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Aripiprazole 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Placebo Placebo QD for 6 weeks
Overall Study STARTED	42	89	90	93	50	95
Overall Study COMPLETED	20	52	53	56	34	53
Overall Study NOT COMPLETED	22	37	37	37	16	42

Reasons for withdrawal

Reasons for withdrawal
Measure	OPC-34712 0.25 mg 0.25 mg once daily (QD) for 6 weeks	OPC-34712 Low-dose 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 Mid-dose 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 High Dose 5.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Aripiprazole 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Placebo Placebo QD for 6 weeks
Overall Study Switched to Open Label Rescue	7	17	11	11	4	15
Overall Study Lost to Follow-up	0	0	0	0	1	1
Overall Study Adverse Event	3	4	5	11	3	5
Overall Study Withdrawal by Subject	5	13	15	11	4	13
Overall Study Protocol Violation	1	0	1	0	0	0
Overall Study Lack of Efficacy	6	3	5	4	4	8

Baseline Characteristics

Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 and Aripiprazole for Treatment of Acute Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OPC-34712 0.25 mg n=42 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=89 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 High-dose n=93 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Placebo n=95 Participants Placebo QD for 6 weeks	Total n=459 Participants Total of all reporting groups
Age, Continuous	40.4 Years STANDARD_DEVIATION 9.1 • n=39 Participants	39.2 Years STANDARD_DEVIATION 10.3 • n=41 Participants	37.4 Years STANDARD_DEVIATION 11.1 • n=35 Participants	39.5 Years STANDARD_DEVIATION 11.1 • n=31 Participants	40.8 Years STANDARD_DEVIATION 11 • n=146 Participants	38.8 Years STANDARD_DEVIATION 11.4 • n=19 Participants	39.1 Years STANDARD_DEVIATION 10.6 • n=147 Participants
Sex: Female, Male Female	15 Participants n=39 Participants	36 Participants n=41 Participants	30 Participants n=35 Participants	38 Participants n=31 Participants	16 Participants n=146 Participants	37 Participants n=19 Participants	172 Participants n=147 Participants
Sex: Female, Male Male	27 Participants n=39 Participants	53 Participants n=41 Participants	60 Participants n=35 Participants	55 Participants n=31 Participants	34 Participants n=146 Participants	58 Participants n=19 Participants	287 Participants n=147 Participants

PRIMARY outcome

Timeframe: Baseline to Week 6

Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The last observation carried forward (LOCF) method was used to impute missing data.

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=41 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=88 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=92 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=93 Participants Placebo QD for 6 weeks
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase)	-9.76 Units on a scale Standard Deviation 19.29	-18.73 Units on a scale Standard Deviation 20.27	-16.19 Units on a scale Standard Deviation 18.55	-18.25 Units on a scale Standard Deviation 20.49	-17.98 Units on a scale Standard Deviation 21.32	-14.40 Units on a scale Standard Deviation 20.13

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impute missing data.

The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS positive subscale score is the sum of the rating scores for the 7 positive scale items from the PANSS panel. The PANSS positive subscale score ranges from 7-49, with higher scores indicating more severe symptoms.

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=41 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=88 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=92 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=93 Participants Placebo QD for 6 weeks
Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase)	-3.22 Units on a scale Standard Deviation 5.26	-5.97 Units on a scale Standard Deviation 7.12	-4.94 Units on a scale Standard Deviation 6.17	-5.98 Units on a scale Standard Deviation 6.72	-6.60 Units on a scale Standard Deviation 7.16	-4.82 Units on a scale Standard Deviation 6.34

SECONDARY outcome

Timeframe: Baseline to Week 6

The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. PANSS negative subscale score is the sum of the rating scores for the 7 negative scale items from the PANSS panel. The PANSS negative subscale score ranges from 7-49, with higher scores indicating more severe symptoms.

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=42 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=89 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=93 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=95 Participants Placebo QD for 6 weeks
Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase)	-1.93 Units on a scale Standard Deviation 5.24	-3.61 Units on a scale Standard Deviation 5.15	-3.84 Units on a scale Standard Deviation 5.09	-3.99 Units on a scale Standard Deviation 5.40	-3.00 Units on a scale Standard Deviation 5.74	-3.17 Units on a scale Standard Deviation 4.88

SECONDARY outcome

Timeframe: Baseline to Week 6

The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains. The rating is based on four main areas: (a) socially useful activities, including work and study; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The ratings are converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Ratings from 71-100 reflect only mild difficulties. Ratings from 31-70 reflect manifest disabilities of various degrees. Ratings from 1-30 reflect functioning so poor that intensive support or supervision is needed.

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=39 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=86 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=84 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=90 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=90 Participants Placebo QD for 6 weeks
Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase)	4.54 Units on a scale Standard Deviation 13.25	11.36 Units on a scale Standard Deviation 14.84	10.67 Units on a scale Standard Deviation 15.21	12.17 Units on a scale Standard Deviation 14.72	10.66 Units on a scale Standard Deviation 13.13	7.56 Units on a scale Standard Deviation 14.90

SECONDARY outcome

Timeframe: Baseline to Week 6

The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices include the following: 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=41 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=88 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=92 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=93 Participants Placebo QD for 6 weeks
Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase)	-0.39 Units on a scale Standard Deviation 0.86	-0.99 Units on a scale Standard Deviation 1.29	-0.87 Units on a scale Standard Deviation 1.11	-1.10 Units on a scale Standard Deviation 1.24	-1.00 Units on a scale Standard Deviation 1.21	-0.82 Units on a scale Standard Deviation 1.16

SECONDARY outcome

Timeframe: Week 6

The rater or investigator rated the particpant's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the participant's condition at baseline prior to the first dose of double-blind study medication. Response choices included the following: 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=41 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=88 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=92 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=93 Participants Placebo QD for 6 weeks
Mean Clinical Global Impression - Improvement (CGI-I) at Week 6	3.66 Units on a scale Standard Deviation 1.48	3.08 Units on a scale Standard Deviation 1.58	3.17 Units on a scale Standard Deviation 1.45	3.04 Units on a scale Standard Deviation 1.50	3.04 Units on a scale Standard Deviation 1.52	3.34 Units on a scale Standard Deviation 1.54

SECONDARY outcome

Timeframe: Week 6

Response rate was defined as a reduction of ≥ 30% from baseline in PANSS Total Score; or a CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=42 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=89 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=93 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=95 Participants Placebo QD for 6 weeks
Response Rate at Week 6	40.5 Percentage of participants	57.3 Percentage of participants	46.7 Percentage of participants	51.6 Percentage of participants	60.0 Percentage of participants	49.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 6

Efficacy-related discontinuation rate was assessed

Outcome measures

Outcome measures
Measure	OPC-34712 0.25 mg n=42 Participants 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=89 Participants 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 Mid-dose n=90 Participants 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment , the physician could request a dose increase, if needed for efficacy, based on clinical judgment	OPC-34712 High-dose n=93 Participants 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Aripiprazole n=50 Participants 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=95 Participants Placebo QD for 6 weeks
Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712	31 Percentage of participants	22.5 Percentage of participants	17.8 Percentage of participants	16.1 Percentage of participants	16.0 Percentage of participants	24.2 Percentage of participants

Adverse Events

OPC-34712 0.25 mg

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

OPC-34712 Low-dose

Serious events: 3 serious events

Other events: 41 other events

Deaths: 0 deaths

OPC-34712 Mid-dose

Serious events: 5 serious events

Other events: 36 other events

Deaths: 0 deaths

OPC-34712 High-dose

Serious events: 4 serious events

Other events: 52 other events

Deaths: 0 deaths

Aripiprazole

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OPC-34712 0.25 mg n=42 participants at risk 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=89 participants at risk 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 Mid-dose n=90 participants at risk 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 High-dose n=93 participants at risk 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Aripiprazole n=50 participants at risk 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=95 participants at risk Placebo QD
General disorders Death	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.0% 1/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Nervous system disorders Complex partial seizures	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.0% 1/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Nervous system disorders Dizziness	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Anxiety	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Psychotic disorder	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Schizophrenia	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Schizophrenia, paranoid type	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.

Other adverse events

Other adverse events
Measure	OPC-34712 0.25 mg n=42 participants at risk 0.25 mg QD for 6 weeks	OPC-34712 Low-dose n=89 participants at risk 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 Mid-dose n=90 participants at risk 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	OPC-34712 High-dose n=93 participants at risk 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	Aripiprazole n=50 participants at risk 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	Placebo n=95 participants at risk Placebo QD
Gastrointestinal disorders Diarrhoea	7.1% 3/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	5.6% 5/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.3% 4/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	8.0% 4/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.2% 3/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Gastrointestinal disorders Dyspepsia	9.5% 4/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.5% 4/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.3% 3/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.3% 4/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.0% 1/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	7.4% 7/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Gastrointestinal disorders Nausea	2.4% 1/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.5% 4/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	7.8% 7/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.5% 6/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.0% 1/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.1% 2/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Gastrointestinal disorders Vomiting	4.8% 2/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.2% 2/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.7% 6/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.2% 2/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.0% 3/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.3% 6/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Investigations Blood creatine phosphokinase increased	2.4% 1/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.2% 2/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	5.4% 5/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Investigations Weight increased	2.4% 1/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.7% 6/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	10.0% 9/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.5% 6/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.0% 3/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.2% 3/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Musculoskeletal and connective tissue disorders Back pain	7.1% 3/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.2% 2/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.3% 3/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.2% 3/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Nervous system disorders Akathisia	2.4% 1/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.7% 6/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	5.6% 5/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	15.1% 14/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.0% 2/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.2% 4/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Nervous system disorders Dizziness	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.5% 4/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.2% 2/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	5.4% 5/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.0% 1/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.2% 3/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Nervous system disorders Extrapyramidal disorder	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.4% 3/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.3% 3/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.5% 6/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.0% 2/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.2% 4/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Nervous system disorders Headache	14.3% 6/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	9.0% 8/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	14.4% 13/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	7.5% 7/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.0% 3/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	10.5% 10/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Nervous system disorders Somnolence	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.4% 3/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	3.3% 3/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	5.4% 5/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.1% 2/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Agitation	9.5% 4/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.5% 4/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.4% 4/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	7.5% 7/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	10.0% 5/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.2% 4/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Anxiety	11.9% 5/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	7.9% 7/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.7% 6/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	10.8% 10/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	10.0% 5/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	10.5% 10/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Restlessness	0.00% 0/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.2% 2/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.0% 3/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.1% 2/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 3/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	1.1% 1/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	0.00% 0/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Gastrointestinal disorders Constipation	4.8% 2/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	4.5% 4/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.2% 2/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	6.5% 6/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	2.0% 1/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	8.4% 8/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Psychiatric disorders Insomnia	9.5% 4/42 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	13.5% 12/89 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	10.0% 9/90 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	9.7% 9/93 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	8.0% 4/50 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.	16.8% 16/95 • Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.

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