Trial Outcomes & Findings for Lurasidone HCl - A Long Term Phase 3 Study of Patients With Chronic Schizophrenia (NCT NCT00789698)

NCT ID: NCT00789698

Last Updated: 2015-06-12

Results Overview

Time to relapse will be defined as the earliest occurrence of any of the following: * Worsening of \>= 30% positive and negative syndrome scale total score from NCT00790192 and clinical global impression-severity sub-scale \>=3 * rehospitalization for worsening of psychosis * emergence of suicidal ideation, homicidal ideation and/or risk of harm to self or others Comparison of time to relapse of psychotic symptoms between lurasidone and quetiapine XR after 1 year as analyzed using the Cox proportional hazard model with country as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

240 participants

Primary outcome timeframe

12 Months

Results posted on

2015-06-12

Participant Flow

Patients transitioned from the acute phase study (D1050233 -NCT00790192) to the current study (D1050234) in a non-randomized fashion.

Participant milestones

Participant milestones
Measure
Lurasidone 80mg
Lurasidone 80mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Lurasidone 160 mg
Lurasidone 160mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Placebo-Lurasidone
Placebo in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study
Quetiapine-Quetiapine
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Overall Study
STARTED
72
79
56
85
Overall Study
COMPLETED
32
46
29
33
Overall Study
NOT COMPLETED
40
33
27
52

Reasons for withdrawal

Reasons for withdrawal
Measure
Lurasidone 80mg
Lurasidone 80mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Lurasidone 160 mg
Lurasidone 160mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Placebo-Lurasidone
Placebo in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study
Quetiapine-Quetiapine
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Overall Study
Lack of Efficacy
10
4
5
18
Overall Study
Adverse Event
5
5
3
4
Overall Study
Lost to Follow-up
5
5
2
9
Overall Study
Protocol Violation
6
1
2
1
Overall Study
Withdrawal by Subject
14
15
12
19
Overall Study
Administrative
0
3
3
1

Baseline Characteristics

Lurasidone HCl - A Long Term Phase 3 Study of Patients With Chronic Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Lurasidone 80mg
n=72 Participants
Lurasidone 80mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Lurasidone 160 mg
n=79 Participants
Lurasidone 160mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Placebo-Lurasidone
n=56 Participants
Placebo in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study
Quetiapine-Quetiapine
n=85 Participants
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Total
n=292 Participants
Total of all reporting groups
Age, Continuous
36.6 years
STANDARD_DEVIATION 11.7 • n=5 Participants
37.6 years
STANDARD_DEVIATION 11.7 • n=7 Participants
37.5 years
STANDARD_DEVIATION 11.4 • n=5 Participants
38.5 years
STANDARD_DEVIATION 10.4 • n=4 Participants
37.6 years
STANDARD_DEVIATION 11.3 • n=21 Participants
Sex: Female, Male
Female
16 Participants
n=5 Participants
27 Participants
n=7 Participants
21 Participants
n=5 Participants
33 Participants
n=4 Participants
97 Participants
n=21 Participants
Sex: Female, Male
Male
56 Participants
n=5 Participants
52 Participants
n=7 Participants
35 Participants
n=5 Participants
52 Participants
n=4 Participants
195 Participants
n=21 Participants
Region of Enrollment
United States
18 participants
n=5 Participants
15 participants
n=7 Participants
14 participants
n=5 Participants
23 participants
n=4 Participants
70 participants
n=21 Participants
Region of Enrollment
Ukraine
17 participants
n=5 Participants
15 participants
n=7 Participants
9 participants
n=5 Participants
18 participants
n=4 Participants
59 participants
n=21 Participants
Region of Enrollment
Romania
6 participants
n=5 Participants
9 participants
n=7 Participants
2 participants
n=5 Participants
10 participants
n=4 Participants
27 participants
n=21 Participants
Region of Enrollment
Russian Federation
11 participants
n=5 Participants
15 participants
n=7 Participants
12 participants
n=5 Participants
17 participants
n=4 Participants
55 participants
n=21 Participants
Region of Enrollment
Colombia
5 participants
n=5 Participants
3 participants
n=7 Participants
3 participants
n=5 Participants
4 participants
n=4 Participants
15 participants
n=21 Participants
Region of Enrollment
India
15 participants
n=5 Participants
22 participants
n=7 Participants
16 participants
n=5 Participants
13 participants
n=4 Participants
66 participants
n=21 Participants

PRIMARY outcome

Timeframe: 12 Months

Population: The population for relapse analyses is the relapse population which consists of those subjects who are enrolled in the present study, demonstrated response to 6 weeks of treatment with either lurasidone or quetiapine XR in study D1050233-NCT 00790192, and who took at least one dose of study medication in the present study.

Time to relapse will be defined as the earliest occurrence of any of the following: * Worsening of \>= 30% positive and negative syndrome scale total score from NCT00790192 and clinical global impression-severity sub-scale \>=3 * rehospitalization for worsening of psychosis * emergence of suicidal ideation, homicidal ideation and/or risk of harm to self or others Comparison of time to relapse of psychotic symptoms between lurasidone and quetiapine XR after 1 year as analyzed using the Cox proportional hazard model with country as a covariate.

Outcome measures

Outcome measures
Measure
Lurasidone-Lurasidone
n=139 Participants
Lurasidone 80 mg/day or lurasidone 160 mg/day in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study.
Quetiapine-Quetiapine
n=79 Participants
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Relapse of Psychotic Symptoms
29 participants
21 participants
Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: Baseline and 6 Months

Population: The population is the intent to treat population which consists of those enrolled subjects who receive at least one dose of study medication and have either a PANSS or CGI-S baseline and post baseline measurements

The battery has seven outcome measures that measure the cognitive constructs. The seven domains are: detection, identification, one back task, international shopping list task, one card learning task, Groton maze learning task and social emotional matching. The standardized scores for each subject at each assessment will then be averaged to yield a composite score. There are no maximum or minimum values, however a higher score indicates improved performance on the cognitive constructs. The change score is change from baseline to month 6.

Outcome measures

Outcome measures
Measure
Lurasidone-Lurasidone
n=86 Participants
Lurasidone 80 mg/day or lurasidone 160 mg/day in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study.
Quetiapine-Quetiapine
n=41 Participants
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Change From the Acute Phase Baseline to Month 6 of the Double-blind Treatment in the CogState Computerized Cognitive Scores.
0.22 units on a scale
Interval 0.06 to 0.38
-0.03 units on a scale
Interval -0.26 to 0.2

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: The population is the intent to treat population which consists of those enrolled subjects who receive at least one dose of study medication and have either a PANSS or CGI-S baseline and post baseline measurements

The PANSS is an interview-based measure of psychopathology severity in adults with psychotic disorders. Thirty items are rated using a Likert scale, from 1 - 7. The PANSS total score is the sum of thirty items ranging from 30 to 210 (higher score representing a worsening in psychosis).

Outcome measures

Outcome measures
Measure
Lurasidone-Lurasidone
n=132 Participants
Lurasidone 80 mg/day or lurasidone 160 mg/day in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study.
Quetiapine-Quetiapine
n=72 Participants
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Positive and Negative Syndrome Scale (PANSS)
-34.6 units on a scale
Interval -38.3 to -30.9
-25.7 units on a scale
Interval -30.9 to -20.6

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: The population is the intent to treat population which consists of those enrolled subjects who receive at least one dose of study medication and have either a PANSS or CGI-S baseline and post baseline measurements

The CGI-S is a clinician-rated assessment of the subject's current illness state on a scale ranging from 1-7, where a higher score is associated with greater illness severity.

Outcome measures

Outcome measures
Measure
Lurasidone-Lurasidone
n=132 Participants
Lurasidone 80 mg/day or lurasidone 160 mg/day in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study.
Quetiapine-Quetiapine
n=72 Participants
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Clinical Global Impression Severity Scale (CGI-S) Scores
-1.9 units on a scale
Interval -2.1 to -1.7
-1.6 units on a scale
Interval -1.9 to -1.4

Adverse Events

Lurasidone 80mg

Serious events: 9 serious events
Other events: 44 other events
Deaths: 0 deaths

Lurasidone 160 mg

Serious events: 6 serious events
Other events: 51 other events
Deaths: 0 deaths

Placebo-Lurasidone

Serious events: 2 serious events
Other events: 35 other events
Deaths: 0 deaths

Quetiapine-Quetiapine

Serious events: 17 serious events
Other events: 53 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Lurasidone 80mg
n=72 participants at risk
Lurasidone 80mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Lurasidone 160 mg
n=79 participants at risk
Lurasidone 160mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Placebo-Lurasidone
n=56 participants at risk
Placebo in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study
Quetiapine-Quetiapine
n=85 participants at risk
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Cardiac disorders
Acute Myocardial Infarction
0.00%
0/72
0.00%
0/79
0.00%
0/56
1.2%
1/85 • Number of events 1
Cardiac disorders
Cardiomyopathy
0.00%
0/72
0.00%
0/79
0.00%
0/56
1.2%
1/85 • Number of events 1
Hepatobiliary disorders
Cholelithiasis
0.00%
0/72
0.00%
0/79
1.8%
1/56 • Number of events 1
0.00%
0/85
Injury, poisoning and procedural complications
Lower Limb Fracture
0.00%
0/72
1.3%
1/79 • Number of events 1
0.00%
0/56
0.00%
0/85
Injury, poisoning and procedural complications
Skeletal Injury
0.00%
0/72
1.3%
1/79 • Number of events 1
0.00%
0/56
0.00%
0/85
Nervous system disorders
Parkinsonism
0.00%
0/72
1.3%
1/79 • Number of events 1
0.00%
0/56
0.00%
0/85
Psychiatric disorders
Agitation
0.00%
0/72
1.3%
1/79 • Number of events 1
0.00%
0/56
2.4%
2/85 • Number of events 2
Psychiatric disorders
Completed Suicide
1.4%
1/72 • Number of events 1
0.00%
0/79
0.00%
0/56
0.00%
0/85
Psychiatric disorders
Psychotic Disorder
4.2%
3/72 • Number of events 3
2.5%
2/79 • Number of events 2
0.00%
0/56
7.1%
6/85 • Number of events 6
Psychiatric disorders
Schizophrenia
4.2%
3/72 • Number of events 3
1.3%
1/79 • Number of events 1
1.8%
1/56 • Number of events 1
10.6%
9/85 • Number of events 9
Psychiatric disorders
Schizophrenia, paranoid type
1.4%
1/72 • Number of events 1
0.00%
0/79
0.00%
0/56
0.00%
0/85
Psychiatric disorders
Suicidal Behavior
1.4%
1/72 • Number of events 1
0.00%
0/79
0.00%
0/56
0.00%
0/85

Other adverse events

Other adverse events
Measure
Lurasidone 80mg
n=72 participants at risk
Lurasidone 80mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Lurasidone 160 mg
n=79 participants at risk
Lurasidone 160mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study.
Placebo-Lurasidone
n=56 participants at risk
Placebo in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study
Quetiapine-Quetiapine
n=85 participants at risk
Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study
Gastrointestinal disorders
Diarrhoea
2.8%
2/72 • Number of events 2
2.5%
2/79 • Number of events 2
7.1%
4/56 • Number of events 4
4.7%
4/85 • Number of events 4
Gastrointestinal disorders
Nausea
4.2%
3/72 • Number of events 3
5.1%
4/79 • Number of events 4
10.7%
6/56 • Number of events 6
2.4%
2/85 • Number of events 3
Gastrointestinal disorders
Toothache
0.00%
0/72
1.3%
1/79 • Number of events 1
5.4%
3/56 • Number of events 3
3.5%
3/85 • Number of events 5
Gastrointestinal disorders
Vomiting
4.2%
3/72 • Number of events 8
3.8%
3/79 • Number of events 4
5.4%
3/56 • Number of events 4
4.7%
4/85 • Number of events 7
Investigations
Weight Increased
4.2%
3/72 • Number of events 6
7.6%
6/79 • Number of events 6
1.8%
1/56 • Number of events 1
8.2%
7/85 • Number of events 8
Nervous system disorders
Akathisia
15.3%
11/72 • Number of events 16
10.1%
8/79 • Number of events 9
10.7%
6/56 • Number of events 9
2.4%
2/85 • Number of events 3
Nervous system disorders
Dystonia
5.6%
4/72 • Number of events 7
1.3%
1/79 • Number of events 1
3.6%
2/56 • Number of events 6
1.2%
1/85 • Number of events 1
Nervous system disorders
Headache
6.9%
5/72 • Number of events 7
13.9%
11/79 • Number of events 16
5.4%
3/56 • Number of events 5
9.4%
8/85 • Number of events 11
Nervous system disorders
Parkinsonism
4.2%
3/72 • Number of events 5
7.6%
6/79 • Number of events 7
16.1%
9/56 • Number of events 12
0.00%
0/85
Nervous system disorders
Somnolence
1.4%
1/72 • Number of events 1
5.1%
4/79 • Number of events 4
1.8%
1/56 • Number of events 1
4.7%
4/85 • Number of events 4
Psychiatric disorders
Anxiety
4.2%
3/72 • Number of events 3
7.6%
6/79 • Number of events 6
3.6%
2/56 • Number of events 3
3.5%
3/85 • Number of events 4
Psychiatric disorders
Insomnia
6.9%
5/72 • Number of events 5
8.9%
7/79 • Number of events 8
7.1%
4/56 • Number of events 4
9.4%
8/85 • Number of events 9
Psychiatric disorders
Schizophrenia
6.9%
5/72 • Number of events 6
2.5%
2/79 • Number of events 2
3.6%
2/56 • Number of events 2
15.3%
13/85 • Number of events 16

Additional Information

Medical Director, CNS

Sunovion Pharmaceuticals

Phone: 1-866-503-6351

Results disclosure agreements

  • Principal investigator is a sponsor employee 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 following completion of study at all sites, the PI shall be free to publish.
  • Publication restrictions are in place

Restriction type: OTHER