Schizophrenia
Conditions
Keywords
Schizophrenia, Latuda, Lurasidone
Brief summary
Lurasidone HCl is a compound developed for the treatment of schizophrenia. This clinical study is designed to test the hypothesis that lurasidone is more efficacious than placebo. The study will also evaluate the safety and tolerability of lurasidone as compared to placebo.
Interventions
DRUGLurasidone
120mg/day
DRUGOlanzapine
15mg/day
DRUGPlacebo comparator
Placebor Comparator
DRUGLurasidone 40 mg tablets
Lurasidone 40 mg tablets
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Provide written informed consent and aged between 18 and 75 years of age. * Meets DSM-IV criteria for a primary diagnosis of schizophrenia. * Not pregnant, if of reproductive potential agrees to remain abstinent or use adequate and reliable contraception for duration of study. * Able and agrees to remain off prior antipsychotic medication for the duration of study. * Good physical health on the basis of medical history, physical examination, and laboratory screening. * Willing and able to comply with the protocol, including the inpatient requirements and outpatient visits.
Exclusion criteria
* Considered by the investigator to be at imminent risk of suicide or injury to self, others or property. * Any chronic organic disease of the CNS (other than schizophrenia). * Used investigational compound within 30 days. * Clinically significant or history of alcohol abuse/alcoholism or drug abuse/dependence within the last 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total PANSS (Positive and Negative Syndrome Scale)Score From Baseline to the End of the Double Blind Treatment Period. | Baseline and 6 weeks | The PANSS is a 30-item rating instrument evaluating the presence/absence and severity of positive, negative and general psychopathology of schizophrenia. The scale was developed from the BPRS and the Psychopathology Rating Scale. All 30 items are rated on a 7-point scale (1=absent; 7=extreme). The total score can range from 30 to 210. Lower scores represent less severity of illness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CGI-S (Clinical Global Impression - Severity) Change From Baseline to the End of the Double-blind Treatment. | 6 weeks | 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. |
Countries
Colombia, India, Lithuania, Philippines, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 40mg Lurasidone 40 mg tablet taken orally once a day. The number of subjects in the participant flow (overall study) is based on the total number of subjects randomized (478). The number of subjects in the baseline characteristics is based on the safety population (475). All randomized subjects who received at least one dose of study medication were included in the safety analysis. One subject who was randomized to the 40 mg treatment group did not take any study medication. | 119 |
| 120mg 3 40 mg tablets taken orally once a day. The number of subjects in the participant flow (overall study) is based on the total number of subjects randomized (478). The number of subjects in the baseline characteristics is based on the safety population (475). All randomized subjects who received at least one dose of study medication were included in the safety analysis. One subject who was randomized to the 120 mg treatment group did not take any study medication. | 118 |
| 15mg Olz 3 5 mg Olanzapine over-encapsulated capsules taken orally once a day. The number of subjects in the participant flow (overall study) is based on the total number of subjects randomized (478). The number of subjects in the baseline characteristics is based on the safety population (475). All randomized subjects who received at least one dose of study medication were included in the safety analysis. One subject who was randomized to the 15 mg Olanzapine treatment group did not take any study medication. | 122 |
| Placebo Placebo to match lurasidone 40mg (tablets or placebo to match olanzapine 5 mg (over-encapsulated). | 116 |
| Total | 475 |
Baseline characteristics
| Characteristic | 40mg | 120mg | 15mg Olz | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 11 | 37.9 years STANDARD_DEVIATION 11.2 | 38.3 years STANDARD_DEVIATION 10.2 | 36.9 years STANDARD_DEVIATION 11.3 | 37.7 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment Colombia | 12 participants | 12 participants | 12 participants | 12 participants | 48 participants |
| Region of Enrollment India | 23 participants | 21 participants | 21 participants | 23 participants | 88 participants |
| Region of Enrollment Lithuania | 7 participants | 7 participants | 7 participants | 8 participants | 29 participants |
| Region of Enrollment Philippines | 7 participants | 6 participants | 8 participants | 5 participants | 26 participants |
| Region of Enrollment United States | 70 participants | 72 participants | 74 participants | 68 participants | 284 participants |
| Sex: Female, Male Female | 26 Participants | 25 Participants | 27 Participants | 26 Participants | 104 Participants |
| Sex: Female, Male Male | 93 Participants | 93 Participants | 95 Participants | 90 Participants | 371 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 90 / 119 | 96 / 118 | 98 / 122 | 84 / 116 |
| serious Total, serious adverse events | 2 / 119 | 6 / 118 | 5 / 122 | 5 / 116 |
Outcome results
Primary
Change in Total PANSS (Positive and Negative Syndrome Scale)Score From Baseline to the End of the Double Blind Treatment Period.
The PANSS is a 30-item rating instrument evaluating the presence/absence and severity of positive, negative and general psychopathology of schizophrenia. The scale was developed from the BPRS and the Psychopathology Rating Scale. All 30 items are rated on a 7-point scale (1=absent; 7=extreme). The total score can range from 30 to 210. Lower scores represent less severity of illness.
Time frame: Baseline and 6 weeks
Population: The primary population for the efficacy analysis was the Intent-to-Treat (ITT) population. All subjects who were randomized, received at least one dose of study medication, and have a Baseline efficacy measurement and at least one post-Baseline efficacy measurement, were in the efficacy analysis in the treatment group to which they were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 40mg | Change in Total PANSS (Positive and Negative Syndrome Scale)Score From Baseline to the End of the Double Blind Treatment Period. | -25.7 Units on a scale |
| 120mg | Change in Total PANSS (Positive and Negative Syndrome Scale)Score From Baseline to the End of the Double Blind Treatment Period. | -23.6 Units on a scale |
| 15mg Olz | Change in Total PANSS (Positive and Negative Syndrome Scale)Score From Baseline to the End of the Double Blind Treatment Period. | -28.7 Units on a scale |
| Placebo | Change in Total PANSS (Positive and Negative Syndrome Scale)Score From Baseline to the End of the Double Blind Treatment Period. | -16.0 Units on a scale |
Comparison: Improvements in PANSS ratings are estimated from 2 prior studies of lurasidone. Assuming lurasidone differs from placebo in change from baseline in PANSS by 6.8 and 10.0 for 40 and 120 mg, respectively, and assuming a standard deviation of 19.1, then n=120 subjects per group provides approximately 97% power (at α=0.05, two-sided) to reject the null hypothesis of no difference from placebo for at least 1 dose. This calculation uses Bonferroni's procedure for controlling pairwise differences.p-value: <0.05Mixed Models Analysis
Secondary
CGI-S (Clinical Global Impression - Severity) Change From Baseline to the End of the Double-blind Treatment.
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.
Time frame: 6 weeks
Population: The primary population for the efficacy analysis was the Intent-to-Treat (ITT) population. All subjects who were randomized, received at least one dose of study medication, and have a Baseline efficacy measurement and at least one post-Baseline efficacy measurement, were in the efficacy analysis in the treatment group to which they were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 40mg | CGI-S (Clinical Global Impression - Severity) Change From Baseline to the End of the Double-blind Treatment. | -1.5 scale |
| 120mg | CGI-S (Clinical Global Impression - Severity) Change From Baseline to the End of the Double-blind Treatment. | -1.4 scale |
| 15mg Olz | CGI-S (Clinical Global Impression - Severity) Change From Baseline to the End of the Double-blind Treatment. | -1.5 scale |
| Placebo | CGI-S (Clinical Global Impression - Severity) Change From Baseline to the End of the Double-blind Treatment. | -1.1 scale |
p-value: <0.05Mixed Models Analysis