Trial Outcomes & Findings for This is an Open-label, Multi-center, Extension Study Designed to Evaluate the Longer Term Safety, Tolerability and Effectiveness of Lurasidone, Flexibly Dosed, Adjunctive to Lithium or Divalproex for the Treatment of Subjects With Bipolar I Disorder Who Have Participated in Study D1050296 (NCT NCT01575561)

NCT ID: NCT01575561

Last Updated: 2016-08-22

Results Overview

Number of subjects with treatment emergent AEs, SAEs, and TEAEs leading to discontinuation

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 377 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2016-08-22

Participant Flow

Participant milestones

Measure	Lurasidone Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Overall Study STARTED	377
Overall Study COMPLETED	338
Overall Study NOT COMPLETED	39

Reasons for withdrawal

Measure	Lurasidone Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Overall Study Adverse Event	9
Overall Study Lack of Efficacy	8
Overall Study Lost to Follow-up	6
Overall Study Protocol Violation	4
Overall Study Withdrawal by Subject	11
Overall Study administration	1

Baseline Characteristics

This is an Open-label, Multi-center, Extension Study Designed to Evaluate the Longer Term Safety, Tolerability and Effectiveness of Lurasidone, Flexibly Dosed, Adjunctive to Lithium or Divalproex for the Treatment of Subjects With Bipolar I Disorder Who Have Participated in Study D1050296

Baseline characteristics by cohort

Measure	Lurasidone n=377 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Age, Categorical <=18 years	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	359 Participants n=5 Participants
Age, Categorical >=65 years	17 Participants n=5 Participants
Age, Continuous	45.5 years STANDARD_DEVIATION 12.27 • n=5 Participants
Sex: Female, Male Female	206 Participants n=5 Participants
Sex: Female, Male Male	171 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	315 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	28 Participants n=5 Participants
Race (NIH/OMB) White	327 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants
Region of Enrollment Czech Republic	40 participants n=5 Participants
Region of Enrollment Russian Federation	42 participants n=5 Participants
Region of Enrollment Argentina	30 participants n=5 Participants
Region of Enrollment Hungary	21 participants n=5 Participants
Region of Enrollment United States	95 participants n=5 Participants
Region of Enrollment Japan	13 participants n=5 Participants
Region of Enrollment Poland	37 participants n=5 Participants
Region of Enrollment Slovakia	5 participants n=5 Participants
Region of Enrollment Bulgaria	34 participants n=5 Participants
Region of Enrollment France	8 participants n=5 Participants
Region of Enrollment Chile	17 participants n=5 Participants
Region of Enrollment Serbia	35 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Number of subjects with treatment emergent AEs, SAEs, and TEAEs leading to discontinuation

Outcome measures

Measure	Lurasidone n=377 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Treatment-emergent Adverse Events and Treatment-emergent Adverse Events Leading to Discontinuation and Serious Adverse Events at Least 1 TEAE potentially related to study drug	155 participants
Treatment-emergent Adverse Events and Treatment-emergent Adverse Events Leading to Discontinuation and Serious Adverse Events subjects with at least one TEAE potentially relate	69 participants
Treatment-emergent Adverse Events and Treatment-emergent Adverse Events Leading to Discontinuation and Serious Adverse Events at least 1 treatment emergent SAE	14 participants
Treatment-emergent Adverse Events and Treatment-emergent Adverse Events Leading to Discontinuation and Serious Adverse Events at least 1 treatment emergent SAE related to drug	1 participants
Treatment-emergent Adverse Events and Treatment-emergent Adverse Events Leading to Discontinuation and Serious Adverse Events at least 1 TEAE leading to discontinuation	9 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks (LOCF)

Population: only 351 of the 377 subjects had the QIDS-SR16 assessment at week 12 (LOCF)

The QIDS-SR16 is a 16-item self-report measure of depressive symptomatology which uses a computerized assessment interface for administration. The scoring system for the QIDS-SR16 converts responses to 16 separate items into nine DSM-IV symptom criterion domains. The nine domains comprise: depressed mood (Item 5); concentration/decision making (Item 10); self outlook (Item 11); suicidal ideation (Item 12); decreased interest (Item 13); decreased energy (Item 14); sleep disturbance (initial, middle, and late insomnia or hypersomnia) (highest score of Items 1 to 4); appetite/weight disturbance (highest score of Items 6 to 9); and psychomotor disturbance (highest score of Items 15 and 16). The QIDS-SR16 total score is calculated as the sum of the 9 domain scores. The QIDS-SR16 total score ranges from 0 to 27 with a high score indicating more severe symptoms.

Outcome measures

Measure	Lurasidone n=351 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR16) Total Score	-1.0 units on a scale Standard Deviation 3.23

SECONDARY outcome

Timeframe: baseline, 12 weeks (LOCF)

Population: only 359 of the 377 subjects had the PANSS-P assessment at week 12 (LOCF)

The PANSS-P is a subset of items in the PANSS, an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS-P subscale score is the sum of the 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity.

Outcome measures

Measure	Lurasidone n=359 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the Positive and Negative Syndrome Scale Positive Subscale (PANSS P) Score	-0.2 units on a scale Standard Deviation 1.16

SECONDARY outcome

Timeframe: Baseline, 12 weeks (LOCF)

Population: only 375 of the 377 subjects had the YMRD assessment at week 12 (LOCF)

Movement disorders as assessed by Young Mania Rating Scale (YMRS) The YMRS is an 11-item instrument used to assess the severity of mania in subjects with a diagnosis of bipolar disorder. Ratings are based on patient self-reporting, combined with clinician observation (accorded greater score). The YMRS total score is calculated as the sum of the 11 items. The YMRS total score ranges from 0 to 60. Higher scores are associated with greater severity of mania.

Outcome measures

Measure	Lurasidone n=375 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the YMRS Total Score -Mania as Assessed by Young Mania Rating Scale (YMRS)	-1.0 units on a scale Standard Deviation 5.17

SECONDARY outcome

Timeframe: baseline ,Week 12 (LOCF)

Population: Only 375 of the 377 subjects had the MADRS assessment at week 12 (LOCF)

Depression as assessed by Montgomery-Asberg Depression Rating Scale (MADRS) -The MADRS consists of 10 items, each rated on a Likert scale, from 0="Normal" to 6="Most Severe". The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity of depression.

Outcome measures

Measure	Lurasidone n=375 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the MADRS Total Score- Depression as Assessed by Montgomery-Asberg Depression Rating Scale (MADRS)	-1.9 units on a scale Standard Deviation 6.82

SECONDARY outcome

Timeframe: baseline, week 12 (LOCF)

Population: only 375 of the 377 subjects had the CGI-BP-S overall assessment at week 12 (LOCF)

Severity of illness as assessed by the Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) -The CGI-BP-S overall score is a single value, clinician-rated assessment of overall bipolar illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity.

Outcome measures

Measure	Lurasidone n=375 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the CGI-BP-S Overall Score- Severity of Illness as Assessed by the Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S)	-.31 units on a scale Standard Deviation 1.068

SECONDARY outcome

Timeframe: baseline, week 12 (LOCF)

Population: Only 375 of the 377 subjects had the CGI-BP-S mania assessment at week 12 (LOCF)

The CGI-BP-S mania score is a single value, clinician-rated assessment of mania illness severity and ranges from 1=Normal, not at all ill to 7= Among the most extremely ill patients. A higher score is associated with greater illness severity

Outcome measures

Measure	Lurasidone n=375 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the CGI-BP-S Mania Score	-0.13 units on a scale Standard Deviation 0.807

SECONDARY outcome

Timeframe: baseline, week 12 (LOCF)

Population: only 375 of the 377 subjects had the CGI-BP-S depression assessment at Week 12 (LOCF)

The CGI-BP-S depression score is a single value, clinician-rated assessment of depression illness severity and range from 1=normal, not at all ill to 7=Among the most extremely ill patients. A higher score is associated with greater illness severity.

Outcome measures

Measure	Lurasidone n=375 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the CGI-BP-S Depression Scale	-0.27 units on a scale Standard Deviation 0.969

SECONDARY outcome

Timeframe: baseline, week 12 (LOCF)

Population: only 297 of the 377 subjects had the SDS total score at week 12 (LOCF)

The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors in the patient's life are impaired by depressive symptoms. The SDS total score is calculated as the sum of the 3 items. The SDS total score ranges from 0 to 30. Higher scores are associated with greater severity of global functional impairments. If a subject has not worked/studied at all during the past week for reasons unrelated to the disorder, the SDS total score will be set to missing.

Outcome measures

Measure	Lurasidone n=297 Participants Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Change From Baseline to Week 12 (LOCF) in the SDS Total Score	-1.4 units on a scale Standard Deviation 5.98

Adverse Events

Lurasidone

Serious events: 14 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lurasidone n=377 participants at risk Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Blood and lymphatic system disorders anaemia megaloblastic	0.27% 1/377 • Number of events 17 • 12 weeks
Injury, poisoning and procedural complications craniocerebral injury	0.27% 1/377 • Number of events 1 • 12 weeks
Injury, poisoning and procedural complications femur fracture	0.27% 1/377 • Number of events 1 • 12 weeks
Injury, poisoning and procedural complications intentional overdose	0.27% 1/377 • Number of events 1 • 12 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) basal cell carcinoma	0.27% 1/377 • Number of events 1 • 12 weeks
Psychiatric disorders depression	1.1% 4/377 • Number of events 4 • 12 weeks
Psychiatric disorders mania	0.53% 2/377 • Number of events 2 • 12 weeks
Psychiatric disorders bipolar disorder	0.27% 1/377 • Number of events 1 • 12 weeks
Psychiatric disorders emotional distress	0.27% 1/377 • Number of events 1 • 12 weeks
Psychiatric disorders panic attack	0.27% 1/377 • Number of events 1 • 12 weeks
Psychiatric disorders persecutory delusion	0.27% 1/377 • Number of events 1 • 12 weeks
Psychiatric disorders accelerated hyertension	0.27% 1/377 • Number of events 1 • 12 weeks

Other adverse events

Measure	Lurasidone n=377 participants at risk Lurasidone 20, 40, 60,80 mg flexible dose Lurasidone: Lurasidone 20-80 mg taken orally once daily
Gastrointestinal disorders nausea	2.1% 8/377 • Number of events 9 • 12 weeks
Infections and infestations nasopharyngitis	3.4% 13/377 • Number of events 14 • 12 weeks
Nervous system disorders headache	4.0% 15/377 • Number of events 18 • 12 weeks
Nervous system disorders akathisia	3.2% 12/377 • Number of events 13 • 12 weeks
Psychiatric disorders insomnia	2.9% 11/377 • Number of events 12 • 12 weeks

Additional Information

CNS Medical Director

Sunovion Pharmaceuticals Inc.

Phone: 1-866-503-6351

Email: clinicaltrialdisclosure@sunvion.com

Results disclosure agreements

• Principal investigator is a sponsor employee In the event the Study is part of a multi-center study, the first publication of the results of the study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.
• Publication restrictions are in place

Restriction type: OTHER