Trial Outcomes & Findings for Lurasidone Low-Dose - High-Dose Study Study (NCT NCT01821378)

Last Updated: 2016-07-21

Results Overview

The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. 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 total score is the sum of all 30 items and ranges from 30 through 210. A higher score is associated with greater illness severity.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

412 participants

Primary outcome timeframe

Baseline to 6 Weeks

Results posted on

2016-07-21

Participant Flow

Participant milestones

Participant milestones
Measure	Lurasidone 20 mg Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2: Lurasidone 80 mg once daily Placebo: Once Daily	Lurasidone 80 mg - 160 mg Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2 Lurasidone: Lurasidone 20 mg once daily Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2: Lurasidone 80 mg once daily Placebo: Once Daily	Placebo Placebo Comparator 20 or 80 mg once daily Lurasidone: Lurasidone 20 mg once daily Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2: Lurasidone 80 mg once daily Placebo: Once Daily
Overall Study STARTED	101	199	112
Overall Study COMPLETED	74	145	70
Overall Study NOT COMPLETED	27	54	42

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lurasidone Low-Dose - High-Dose Study Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lurasidone 20 mg n=101 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=198 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=112 Participants Placebo: Once Daily	Total n=411 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	4 Participants n=4 Participants	0 Participants n=27 Participants	4 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	99 Participants n=93 Participants	192 Participants n=4 Participants	112 Participants n=27 Participants	403 Participants n=483 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	4 Participants n=483 Participants
Age, Continuous	41.5 years STANDARD_DEVIATION 10.96 • n=93 Participants	40.5 years STANDARD_DEVIATION 11.44 • n=4 Participants	40.7 years STANDARD_DEVIATION 11.58 • n=27 Participants	40.8 years STANDARD_DEVIATION 11.34 • n=483 Participants
Sex: Female, Male Female	36 Participants n=93 Participants	79 Participants n=4 Participants	34 Participants n=27 Participants	149 Participants n=483 Participants
Sex: Female, Male Male	65 Participants n=93 Participants	119 Participants n=4 Participants	78 Participants n=27 Participants	262 Participants n=483 Participants
Region of Enrollment Colombia	3 participants n=93 Participants	9 participants n=4 Participants	7 participants n=27 Participants	19 participants n=483 Participants
Region of Enrollment Russian Federation	23 participants n=93 Participants	49 participants n=4 Participants	27 participants n=27 Participants	99 participants n=483 Participants
Region of Enrollment Romania	22 participants n=93 Participants	38 participants n=4 Participants	18 participants n=27 Participants	78 participants n=483 Participants
Region of Enrollment United States	31 participants n=93 Participants	59 participants n=4 Participants	38 participants n=27 Participants	128 participants n=483 Participants
Region of Enrollment Ukraine	16 participants n=93 Participants	31 participants n=4 Participants	13 participants n=27 Participants	60 participants n=483 Participants
Region of Enrollment Slovakia	6 participants n=93 Participants	12 participants n=4 Participants	9 participants n=27 Participants	27 participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline to 6 Weeks

Population: Intent to treat population - there was one subject randomized but not treated with study medication, therefore excluded from ITT population

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=101 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=198 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=112 Participants Placebo: Once Daily
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 for Lurasidone 20 mg and 80-160 mg Versus Placebo.	-17.6 units on a scale Standard Error 1.93	-24.9 units on a scale Standard Error 1.40	-14.5 units on a scale Standard Error 1.89

SECONDARY outcome

Timeframe: Baseline to 6 Weeks

Population: Intent to treat population

The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale (0-7), where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes.

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=101 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=198 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=112 Participants Placebo: Once Daily
Change in Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 6 for Lurasidone 20 mg and 80-160 mg Versus Placebo.	-0.93 units on a scale Standard Error 0.105	-1.30 units on a scale Standard Error 0.076	-0.73 units on a scale Standard Error 0.103

SECONDARY outcome

Timeframe: Baseline to 6 Weeks

Population: Intent to treat population - only 379 subjects had at least one post-baseline MADRS assessment.

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.

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=93 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=178 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=108 Participants Placebo: Once Daily
Change From Baseline to Week 6 for the Lurasidone 20 mg, and Lurasidone 80 - 160 mg Groups Versus the Placebo Group in the Montgomery-Asberg Depression Rating Scale Total Score	-2.0 units on a scale Standard Error 0.57	-3.7 units on a scale Standard Error 0.41	-1.7 units on a scale Standard Error 0.53

SECONDARY outcome

Timeframe: 6 Weeks

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=101 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=198 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=112 Participants Placebo: Once Daily
Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Score (PANSS) Total Score at Week 6	44 percentage of participants	53 percentage of participants	73 percentage of participants

SECONDARY outcome

Timeframe: week 2 to week 6

Population: ENR (early non-responders) Intent to treat (ITT) population: of the 199 subjects who randomized to 80 mg group, only 95 subjects are early non-responders at week 2, therefore they are included in the ENR ITT population.

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=52 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=43 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo Placebo: Once Daily
Change From Week 2 to Week 6 for the ENR (Early Non-responders) Lurasidone 160mg Group vs the ENR (Early Non-responders) Lurasidone 80 mg Group in the Following: PANSS Total Score	-8.9 units on a scale Standard Error 2.20	-16.6 units on a scale Standard Error 2.47	—

SECONDARY outcome

Timeframe: baseline to week 6

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=52 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=42 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=108 Participants Placebo: Once Daily
Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the MADRS Total Score	-2.5 units on a scale Standard Error 0.89	-3.5 units on a scale Standard Error 1.00	-1.7 units on a scale Standard Error 0.59

SECONDARY outcome

Timeframe: week 2 to week 6

Population: ENR Intent to treat population

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=52 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=43 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo Placebo: Once Daily
Change From Week 2 to Week 6 for ENR Lurasidone 80 mg vs. ENR Lurasidone 160 mg in CGI-S Score	-0.61 units on a scale Standard Error 0.116	-0.96 units on a scale Standard Error 0.134	—

SECONDARY outcome

Timeframe: Baseline to week 6

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=52 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=43 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=112 Participants Placebo: Once Daily
Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the PANSS Total Score	-14.4 units on a scale Standard Error 2.69	-21.7 units on a scale Standard Error 3.00	-14.4 units on a scale Standard Error 1.98

SECONDARY outcome

Timeframe: baseline to week 6

The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale, where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes. Reason for the discrepancy of the LS mean (SE) for placebo in outcome 2 and outcome 9 is because the different MMRM model used in outcome 2 and outcome 9. The treatment groups included in the MMRM model for outcome 2 are placebo, lurasidone 20 mg, and lurasidone 80-160 mg. The treatment groups included in the MMRM model for outcome 9 are placebo, ENR lurasidone 80 mg, and ENR lurasidone 160 mg.

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=52 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=43 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=112 Participants Placebo: Once Daily
Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the CGI-S Score	-0.83 units on a scale Standard Error 0.143	-1.31 units on a scale Standard Error 0.160	-0.73 units on a scale Standard Error 0.106

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 Weeks

Population: Intent to treat population

The GAF is a numeric scale (0 through 100) that measures a patient's overall level of psychological, social, and occupation functioning. It is designed to guide clinicians through a methodical and comprehensive consideration of all aspects of a patient's symptoms and functioning. The scale begins at 100 - superior functioning - to 0 - inadequate information.

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=101 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=198 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=112 Participants Placebo: Once Daily
Change From Baseline to Week 6 for the Lurasidone 20 mg and Lurasidone 80 - 160 mg Groups Compared to the Placebo Group in the GAF Score	11.5 units on a scale Standard Error 1.43	15.8 units on a scale Standard Error 1.04	9.2 units on a scale Standard Error 1.40

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

Population: Intent to treat population: there are only 368 subjects who had at least one post-baseline Euroqol (EQ-5D) assessments.

The EQ-5D is a standardized measure of health state consisting of two parts: a) EQ-5D measuring mobility, self-care, pain/discomfort, usual activities, and anxiety/depression on a 0 2 scale with lower scores indicating improvement, and b) a 20-cm visual analogue scale (VAS) for health status rating on a 0-100 scale with higher scores indicating improvement. EQ-5D health states, defined by the EQ-5D descriptive system, may be converted into a single summary index (i.e. the EQ-5D index score) by applying a formula that essentially attaches values (also called weights) to each of the levels in each dimension. The EQ-5D Index scores ranged from -0.429 to 1.000. Generally higher observed EQ-5D Index scores indicate a better degree of health.

Outcome measures

Outcome measures
Measure	Lurasidone 20 mg n=92 Participants Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=173 Participants Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo n=103 Participants Placebo: Once Daily
Change From Baseline to Week 6 for the Lurasidone 20 mg and Lurasidone 80 - 160 mg Groups Compared to the Placebo Group in the Euroqol (EQ-5D) Index Score	0.041 units on a scale Standard Error 0.024	0.095 units on a scale Standard Error 0.018	-0.042 units on a scale Standard Error 0.023

Adverse Events

Lurasidone 20 mg

Serious events: 3 serious events

Other events: 43 other events

Deaths: 0 deaths

Lurasidone 80-160 mg

Serious events: 6 serious events

Other events: 92 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lurasidone 20 mg n=101 participants at risk Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=198 participants at risk Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2 (one subject who was randomized was not treated with study drug, therefore, excluded from the safety population).	Placebo n=112 participants at risk Placebo: Once Daily
General disorders Therapuetuc Response Delayed	0.00% 0/101 • 6 Weeks	0.00% 0/198 • 6 Weeks	0.89% 1/112 • Number of events 1 • 6 Weeks
Injury, poisoning and procedural complications Fall	0.00% 0/101 • 6 Weeks	0.51% 1/198 • Number of events 1 • 6 Weeks	0.00% 0/112 • 6 Weeks
Injury, poisoning and procedural complications Fibula Fracture	0.00% 0/101 • 6 Weeks	0.51% 1/198 • Number of events 1 • 6 Weeks	0.00% 0/112 • 6 Weeks
Injury, poisoning and procedural complications Tibia Fracture	0.00% 0/101 • 6 Weeks	0.51% 1/198 • Number of events 1 • 6 Weeks	0.00% 0/112 • 6 Weeks
Psychiatric disorders Schizophrenia	3.0% 3/101 • Number of events 3 • 6 Weeks	1.5% 3/198 • Number of events 3 • 6 Weeks	3.6% 4/112 • Number of events 4 • 6 Weeks
Psychiatric disorders Psychotic Disorder	0.00% 0/101 • 6 Weeks	1.0% 2/198 • Number of events 2 • 6 Weeks	2.7% 3/112 • Number of events 3 • 6 Weeks

Other adverse events

Other adverse events
Measure	Lurasidone 20 mg n=101 participants at risk Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80-160 mg n=198 participants at risk Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2 (one subject who was randomized was not treated with study drug, therefore, excluded from the safety population).	Placebo n=112 participants at risk Placebo: Once Daily
Gastrointestinal disorders Dyspepsia	2.0% 2/101 • Number of events 2 • 6 Weeks	2.5% 5/198 • Number of events 5 • 6 Weeks	3.6% 4/112 • Number of events 5 • 6 Weeks
Gastrointestinal disorders Nausea	2.0% 2/101 • Number of events 2 • 6 Weeks	8.6% 17/198 • Number of events 21 • 6 Weeks	3.6% 4/112 • Number of events 5 • 6 Weeks
Gastrointestinal disorders Diarrhoea	2.0% 2/101 • Number of events 2 • 6 Weeks	4.0% 8/198 • Number of events 8 • 6 Weeks	2.7% 3/112 • Number of events 3 • 6 Weeks
Gastrointestinal disorders Constipation	3.0% 3/101 • Number of events 4 • 6 Weeks	3.0% 6/198 • Number of events 9 • 6 Weeks	1.8% 2/112 • Number of events 2 • 6 Weeks
Gastrointestinal disorders Vomiting	0.00% 0/101 • 6 Weeks	5.6% 11/198 • Number of events 12 • 6 Weeks	0.89% 1/112 • Number of events 2 • 6 Weeks
Musculoskeletal and connective tissue disorders Myalgia	0.99% 1/101 • Number of events 1 • 6 Weeks	0.00% 0/198 • 6 Weeks	3.6% 4/112 • Number of events 4 • 6 Weeks
Musculoskeletal and connective tissue disorders Back Pain	4.0% 4/101 • Number of events 4 • 6 Weeks	1.5% 3/198 • Number of events 3 • 6 Weeks	0.89% 1/112 • Number of events 1 • 6 Weeks
Nervous system disorders Headache	9.9% 10/101 • Number of events 18 • 6 Weeks	5.6% 11/198 • Number of events 12 • 6 Weeks	7.1% 8/112 • Number of events 12 • 6 Weeks
Nervous system disorders Somnolence	5.0% 5/101 • Number of events 5 • 6 Weeks	3.0% 6/198 • Number of events 6 • 6 Weeks	5.4% 6/112 • Number of events 6 • 6 Weeks
Nervous system disorders Akathisia	5.0% 5/101 • Number of events 9 • 6 Weeks	10.6% 21/198 • Number of events 24 • 6 Weeks	1.8% 2/112 • Number of events 2 • 6 Weeks
Nervous system disorders Sedation	3.0% 3/101 • Number of events 3 • 6 Weeks	3.0% 6/198 • Number of events 6 • 6 Weeks	1.8% 2/112 • Number of events 2 • 6 Weeks
Nervous system disorders Tremor	2.0% 2/101 • Number of events 2 • 6 Weeks	3.0% 6/198 • Number of events 6 • 6 Weeks	1.8% 2/112 • Number of events 2 • 6 Weeks
Nervous system disorders Dizziness	0.99% 1/101 • Number of events 1 • 6 Weeks	3.0% 6/198 • Number of events 6 • 6 Weeks	0.89% 1/112 • Number of events 1 • 6 Weeks
Nervous system disorders Parkinsonism	0.99% 1/101 • Number of events 1 • 6 Weeks	3.0% 6/198 • Number of events 6 • 6 Weeks	0.89% 1/112 • Number of events 1 • 6 Weeks
Psychiatric disorders Insomnia	15.8% 16/101 • Number of events 22 • 6 Weeks	10.6% 21/198 • Number of events 33 • 6 Weeks	21.4% 24/112 • Number of events 33 • 6 Weeks
Psychiatric disorders Agitation	5.0% 5/101 • Number of events 5 • 6 Weeks	4.5% 9/198 • Number of events 9 • 6 Weeks	9.8% 11/112 • Number of events 14 • 6 Weeks
Psychiatric disorders Anxiety	7.9% 8/101 • Number of events 18 • 6 Weeks	4.0% 8/198 • Number of events 9 • 6 Weeks	6.2% 7/112 • Number of events 12 • 6 Weeks
Psychiatric disorders Restlessness	0.00% 0/101 • 6 Weeks	3.0% 6/198 • Number of events 10 • 6 Weeks	3.6% 4/112 • Number of events 9 • 6 Weeks

Additional Information

1-866-503-6351

Sunovion

Phone: 1-866-503-6351

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee There IS agreement between Principal Investigator and Sponsor that restricts PI's rights to discuss or publish trial results after trial is completed. In addition to the \<60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication provided, if a multicenter publication is not forthcoming within 24 months post completion of study at all sites, PI shall be free to publish.
Publication restrictions are in place

Restriction type: OTHER