Trial Outcomes & Findings for A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial (NCT NCT01727726)

Results Overview

To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2182 participants

Primary outcome timeframe

Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).

Results posted on

2018-06-08

Participant Flow

Trial was conducted at 75 trial sites in 7 countries (United States, Russia, Poland, France, Serbia,Germany \& Canada). Phase A non-responders entered Phase B (503 subjects randomized in 2:2:1 (197+100+206) ratio - brexpiprazole/Seroquel extended release tablets/placebo +ADT).

Screening period ranged from a minimum of 7 days to a maximum of 28 days and began when informed consent was signed. The purpose of the screening period was to assess eligibility criteria at 1 or more visits (as necessary to complete screening assessments) and to washout (minimum of 24 hours) prohibited concomitant pharmacotherapy, if applicable.

Participant milestones

Participant milestones
Measure	Brexpiprazole + ADT Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule at 1 mg, 2 mg, 3 mg.	Seroquel XR + ADT Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule at 50 mg, 150 mg, 300 mg.	Placebo + ADT Matching Placebo and assigned ADT Placebo: tablet/capsule
Overall Study STARTED	197	100	206
Overall Study COMPLETED	171	86	186
Overall Study NOT COMPLETED	26	14	20

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brexpiprazole + ADT n=197 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=100 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=206 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule	Total n=503 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	197 Participants n=5 Participants	100 Participants n=7 Participants	206 Participants n=5 Participants	503 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	43.6 years STANDARD_DEVIATION 11.5 • n=5 Participants	44.6 years STANDARD_DEVIATION 11.6 • n=7 Participants	41.8 years STANDARD_DEVIATION 11.7 • n=5 Participants	43 years STANDARD_DEVIATION 11.7 • n=4 Participants
Sex: Female, Male Female	128 Participants n=5 Participants	66 Participants n=7 Participants	149 Participants n=5 Participants	343 Participants n=4 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	34 Participants n=7 Participants	57 Participants n=5 Participants	160 Participants n=4 Participants

PRIMARY outcome

Timeframe: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
Montgomery Asberg Depression Rating Scale (MADRS)	-6.04 Units on a scale Standard Error 0.43	-4.86 Units on a scale Standard Error 0.57	-4.57 Units on a scale Standard Error 0.41

SECONDARY outcome

Timeframe: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for SDS Score in Phase B.

To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale is a measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains ( work/social life/family life/home responsibilities). The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. Scores of 5 and above are associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment.

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
Sheehan Disability Scale (SDS)	-0.97 units on a scale Standard Error 0.12	-0.32 units on a scale Standard Error 0.16	-0.74 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Change from baseline to week 2 and week 4 in Phase B (week 10/12 and week 12/14)

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

Change from end of Phase A in MADRS Total Score. The MADRS was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4. Phase B Week 2	-2.57 units on a scale Standard Error 0.32	-2.26 units on a scale Standard Error 0.41	-1.04 units on a scale Standard Error 0.31
Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4. Phase B Week 4	-4.39 units on a scale Standard Error 0.39	-3.30 units on a scale Standard Error 0.51	-3.22 units on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: From randomization to Phase B week 6 (14/16 weeks after randomization).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for CGI-S score and CGI-I score in Phase B.

Mean change from end of Phase A in Clinical Global Impression - Severity of Illness scale (CGI-S) score and Improvement scale (CGI-I) during double-blind randomized Phase B treatment. CGI-S score assessed how mentally ill the patient was at that time. CGI-S score is calculated from 0 to 7 (0 indicates not assessed 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and7 indicated among the most extremely ill patient). CGI-I score is compared to his/her condition at baseline, how much has the patient changed. CGI-I score is calculated from 0 to 7 (0 indicates not assessed and 7 indicates very much worse).

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
Clinical Global Impression Score CGI-Severity of Illness Scale	3.98 Mean score Standard Deviation 0.56	4.07 Mean score Standard Deviation 0.58	4.02 Mean score Standard Deviation 0.58
Clinical Global Impression Score CGI-Improvement Scale Score	2.55 Mean score Standard Deviation 0.84	2.71 Mean score Standard Deviation 0.87	2.74 Mean score Standard Deviation 0.83

SECONDARY outcome

Timeframe: Phase B week 6 (14/16 weeks after randomization).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment.

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
MADRS Response at Week 6	20 Participants	8 Participants	14 Participants

SECONDARY outcome

Timeframe: Phase B week 6 (14/16 weeks after randomization).

Population: Number of subjects in the Safety Sample who had an end of Phase A (ie, Week 8 or 10) value and at least one post randomization efficacy evaluation for MADRS Total Score in Phase B.

MADRS Remission Rate, where remission was defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score, for every trial week visit during double-blind randomized Phase B treatment.

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
Number of Participants With MADRS	13 Participants	2 Participants	9 Participants

SECONDARY outcome

Timeframe: Phase B week 6 (14/16 weeks after randomization).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

CGI-I Response rate, where response was defined as a CGI-I score of 1 or 2 (very much improved or much improved), during double-blind randomized Phase B treatment.

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
CGI-I Response Rate	100 Participants	48 Participants	79 Participants

SECONDARY outcome

Timeframe: From screening (Day -28 to Day-1) upto post treatment follow-up.

Population: Randomized subjects in Phase B who received at least one dose of double-blind trial medication as indicated on the dosing record.

To evaluate the safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with MDD as AE variables.

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=197 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=100 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=206 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
Number of Participants With Adverse Events Death	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Serious TEAE	0 Participants	1 Participants	1 Participants
Number of Participants With Adverse Events Discontinuation due to TEAE	2 Participants	4 Participants	1 Participants
Number of Participants With Adverse Events Any TEAE	100 Participants	58 Participants	107 Participants

SECONDARY outcome

Timeframe: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale (a self rated questionnaire) was used for measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains (work/school work, social life/leisure activities and family life/home responsibilities). All domains were rated on a score scale ranged from 0 (no impairment) to 10 (most severe). Score of 5 and above indicated significant functional impairment. A total score was addition of the 3 individual scores and the total score ranged from 0 (no impairment) to 30 (most severe).

Outcome measures

Outcome measures
Measure	Brexpiprazole + ADT n=191 Participants Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=99 Participants Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=205 Participants Matching Placebo and assigned ADT Placebo: tablet/capsule
Sheehan Disability Scale (SDS) Individual Item Scores. Work/School Score	-0.59 units on a scale Standard Error 0.16	-0.22 units on a scale Standard Error 0.21	-0.74 units on a scale Standard Error 0.16
Sheehan Disability Scale (SDS) Individual Item Scores. Social Life Score	-1.03 units on a scale Standard Error 0.13	-0.26 units on a scale Standard Error 0.17	-0.70 units on a scale Standard Error 0.12
Sheehan Disability Scale (SDS) Individual Item Scores. Family Life Score	-1.02 units on a scale Standard Error 0.13	-0.34 units on a scale Standard Error 0.18	-0.67 units on a scale Standard Error 0.13

Adverse Events

Brexpiprazole + ADT

Serious events: 0 serious events

Other events: 62 other events

Deaths: 0 deaths

Seroquel XR + ADT

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

Placebo + ADT

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brexpiprazole + ADT n=197 participants at risk Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=100 participants at risk Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=206 participants at risk Matching Placebo and assigned ADT Placebo: tablet/capsule
Neoplasms benign, malignant and unspecified (incl cysts and polyps) malignanat melanoma	0.00% 0/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.0% 1/100 • Number of events 1 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	0.00% 0/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Psychiatric disorders panic attack	0.00% 0/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	0.00% 0/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	0.49% 1/206 • Number of events 1 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.

Other adverse events

Other adverse events
Measure	Brexpiprazole + ADT n=197 participants at risk Brexpiprazole, flexible dose and assigned ADT Brexpiprazole: tablet/capsule	Seroquel XR + ADT n=100 participants at risk Seroquel XR, flexible dose and assigned ADT Seroquel XR: tablet/capsule	Placebo + ADT n=206 participants at risk Matching Placebo and assigned ADT Placebo: tablet/capsule
General disorders Asthenia	2.0% 4/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	2.0% 2/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	0.00% 0/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
General disorders fatigue	1.5% 3/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	4.0% 4/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.5% 3/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Infections and infestations Nasopharyngitis	4.6% 9/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	2.0% 2/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	4.4% 9/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Investigations Weight Increased	3.6% 7/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	4.0% 4/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.9% 4/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Metabolism and nutrition disorders Increased Appetite	2.5% 5/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	5.0% 5/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	0.97% 2/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Nervous system disorders Akathisia	6.1% 12/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	3.0% 3/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.9% 4/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Nervous system disorders Dizziness	3.6% 7/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	3.0% 3/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	2.4% 5/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Nervous system disorders Headache	5.6% 11/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.0% 1/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	4.9% 10/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Nervous system disorders Somnolence	5.6% 11/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	18.0% 18/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	0.97% 2/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Psychiatric disorders Insomnia	2.5% 5/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	3.0% 3/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.9% 4/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Psychiatric disorders Irritability	2.0% 4/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.0% 1/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.5% 3/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
Psychiatric disorders Restlessness	2.5% 5/197 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	1.0% 1/100 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.	0.97% 2/206 • Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up. All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place