Schizophrenia
Conditions
Keywords
Schizophrenia, SM-13496, Latuda, Lurasidone
Brief summary
Lurasidone HCl is a compound being 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 HCl
Once daily
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
To be eligible to enter the study, each patient must comply with the following 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 Score From Baseline to the End of the Double Blind Phase | 6 weeks | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CGI-S From Baseline to the End of the Double-blind Treatment | 6 weeks | Clinical Global Impression of Severity 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. The scale has a single item measured on a 7 point scale from 1 ('normal', not ill) to 7 (extremely ill). |
Countries
France, India, Malaysia, Romania, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lurasidone 40mg Lurasidone 40 mg tablets taken once a day The number of subjects in the participant flow (overall study) is based on the total number of subjects randomized (500). The number of subjects in the baseline characteristics is based on the safety population (489). All randomized subjects who received at least one dose of study medication were included in the safety analysis. This means that 3 subjects were randomized but never received a dose of study drug. | 122 |
| Lurasidone 80mg lurasidone 40m mg tablets taken once/day The number of subjects in the participant flow (overall study) is based on the total number of subjects randomized (500). The number of subjects in the baseline characteristics is based on the safety population (489). All randomized subjects who received at least one dose of study medication were included in the safety analysis. This means that 4 subjects were randomized but never received a dose of study drug. | 119 |
| Lurasidone 120mg Lurasidone 40 mg tablets taken once/day | 124 |
| Placebo Matching placebo to Lurasidone 40 mg taken once/day The number of subjects in the participant flow (overall study) is based on the total number of subjects randomized (500). The number of subjects in the baseline characteristics is based on the safety population (489). All randomized subjects who received at least one dose of study medication were included in the safety analysis. This means that 4 subjects were randomized but never received a dose of study drug. | 124 |
| Total | 489 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative | 2 | 2 | 2 | 1 |
| Overall Study | Adverse Event | 6 | 8 | 7 | 3 |
| Overall Study | Insufficient clinical response | 20 | 7 | 18 | 32 |
| Overall Study | Lost to Follow-up | 4 | 2 | 0 | 6 |
| Overall Study | Withdrawal by Subject | 9 | 18 | 12 | 13 |
Baseline characteristics
| Characteristic | Lurasidone 40mg | Lurasidone 80mg | Lurasidone 120mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 11.1 | 38.6 years STANDARD_DEVIATION 9.5 | 37.7 years STANDARD_DEVIATION 11.2 | 38.2 years STANDARD_DEVIATION 9.9 | 38.8 years STANDARD_DEVIATION 10.5 |
| Region of Enrollment France | 0 participants | 1 participants | 1 participants | 1 participants | 3 participants |
| Region of Enrollment India | 14 participants | 16 participants | 17 participants | 16 participants | 63 participants |
| Region of Enrollment Malaysia | 2 participants | 2 participants | 2 participants | 2 participants | 8 participants |
| Region of Enrollment Romania | 9 participants | 9 participants | 9 participants | 9 participants | 36 participants |
| Region of Enrollment Russian Federation | 14 participants | 15 participants | 13 participants | 15 participants | 57 participants |
| Region of Enrollment Ukraine | 13 participants | 12 participants | 12 participants | 14 participants | 51 participants |
| Region of Enrollment United States | 70 participants | 64 participants | 70 participants | 67 participants | 271 participants |
| Sex: Female, Male Female | 40 Participants | 43 Participants | 32 Participants | 34 Participants | 149 Participants |
| Sex: Female, Male Male | 82 Participants | 76 Participants | 92 Participants | 90 Participants | 340 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 | 96 / 124 | 90 / 121 | 106 / 124 | 85 / 127 |
| serious Total, serious adverse events | 2 / 124 | 3 / 121 | 6 / 124 | 5 / 127 |
Outcome results
Primary
Change in Total PANSS Score From Baseline to the End of the Double Blind Phase
The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
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) |
|---|---|---|
| Lurasidone 40mg | Change in Total PANSS Score From Baseline to the End of the Double Blind Phase | -19.2 scores on a scale |
| Lurasidone 80mg | Change in Total PANSS Score From Baseline to the End of the Double Blind Phase | -23.4 scores on a scale |
| Lurasidone 120mg | Change in Total PANSS Score From Baseline to the End of the Double Blind Phase | -20.5 scores on a scale |
| Placebo | Change in Total PANSS Score From Baseline to the End of the Double Blind Phase | -17.0 scores on a scale |
p-value: <0.05Mixed Models Analysis
Secondary
CGI-S From Baseline to the End of the Double-blind Treatment
Clinical Global Impression of Severity 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. The scale has a single item measured on a 7 point scale from 1 ('normal', not ill) to 7 (extremely ill).
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) |
|---|---|---|
| Lurasidone 40mg | CGI-S From Baseline to the End of the Double-blind Treatment | -1.1 scores on a scale |
| Lurasidone 80mg | CGI-S From Baseline to the End of the Double-blind Treatment | -1.4 scores on a scale |
| Lurasidone 120mg | CGI-S From Baseline to the End of the Double-blind Treatment | -1.2 scores on a scale |
| Placebo | CGI-S From Baseline to the End of the Double-blind Treatment | -1.0 scores on a scale |
p-value: <0.05Mixed Models Analysis