Schizophrenia
Conditions
Keywords
Schizophrenia, Latuda, Lurasidone
Brief summary
The purpose of this study is to evaluate the efficacy of the drug SM-13496 compared to a placebo and to haloperidol in patients with schizophrenia.
Interventions
DRUGLurasidone 20 mg
Lurasidone 20mg/day tablets
DRUGLurasidone 40mg
Lurasidone 40mg/day tablets
DRUGLurasidone 80 mg
Lurasidone 80mg/day - 2 40mg tablets
DRUGHaloperidol 10mg
Haloperidol 10mg/day tablets
DRUGPlacebo
Matching Placebo to Lurasdione and Haloperidol
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* The patient has a primary diagnosis of schizophrenia * The patient has been hospitalized with acute or relapsing schizophrenia within 3 weeks of screening * The patient has had a duration of illness of at least one year. * The patient has a BPRS score of at least 42 at baseline and a score of at least 4 in two or more items of the positive symptom subcluster on the PANSS * The patient is able to remain off antipsychotic medication for a 4 day washout period
Exclusion criteria
* The patient has had psychiatric hospitalizations other than current hospitalizations within 1 month prior to screening. * The patient is considered treatment resistant-Substance abuse-Prolactin level of \> 200 ng/mL at baseline * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score | Baseline and 6 weeks | The BPRS consists of 18 ordered categorical items (from not present to extremely severe, on a 1- to 7-point scale), each developed to assess patient symptomatology in a relatively discrete symptom area. The BPRS will be extracted from the PANSS by adding the scores of the 18 items (P2 to P7, N1, N2, and G1 to G10) of the PANSS and will not be assessed separately. The minimum score on the BPRS is 18 and the maximum is 126. The higher number indicates a worsening of schizophrenia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores | Baseline and 6 weeks | The PANSS Positive and Negative Syndrome Scale)is a 30-item scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. Each item is rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme). Scores range from 30-210 with higher scores representing a worsening of schizophrenia. |
| Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores | Baseline and 6 weeks | The CGI Severity (CGI-S) assesses the severity of illness of the patient relative to the particular population on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). |
| Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores | Baseline and 6 weeks | The MADRS is a 10-item rating scale that assesses apparent and reported sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 20 mg Lurasidone 20 mg oral tablet taken once a day | 71 |
| 40 mg Lurasidone 40 mg oral tablet taken once a day. The number of subjects in the participant flow (overall study) is based on the total number of subjects randomized (356). The number of subjects in the baseline characteristics is based on the safety population (353). All randomized subjects who received at least one dose of study medication were included in the safety analysis. Two subjects who were randomized to the 40 mg treatment group did not take any study medication. | 67 |
| 80 mg Lurasidone 80 mg oral tablet taken once a day | 71 |
| 10 mg Haloperidol 10 mg Haloperidol overencapsulated 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 (356). The number of subjects in the baseline characteristics is based on the safety population (353). 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 10 mg haloperidol treatment group did not take any study medication. | 72 |
| Placebo Oral Capsule matching treatment group taken oce a day | 72 |
| Total | 353 |
Baseline characteristics
| Characteristic | 20 mg | 40 mg | 80 mg | 10 mg Haloperidol | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 10.5 | 42.0 years STANDARD_DEVIATION 10.9 | 42.2 years STANDARD_DEVIATION 8.3 | 40.0 years STANDARD_DEVIATION 10.5 | 41.0 years STANDARD_DEVIATION 9.7 | 41.2 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 19 Participants | 14 Participants | 17 Participants | 91 Participants |
| Sex: Female, Male Male | 51 Participants | 46 Participants | 52 Participants | 58 Participants | 55 Participants | 262 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 49 / 71 | 51 / 67 | 51 / 71 | 58 / 72 | 50 / 72 |
| serious Total, serious adverse events | 4 / 71 | 9 / 67 | 3 / 71 | 5 / 72 | 7 / 72 |
Outcome results
Primary
Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score
The BPRS consists of 18 ordered categorical items (from not present to extremely severe, on a 1- to 7-point scale), each developed to assess patient symptomatology in a relatively discrete symptom area. The BPRS will be extracted from the PANSS by adding the scores of the 18 items (P2 to P7, N1, N2, and G1 to G10) of the PANSS and will not be assessed separately. The minimum score on the BPRS is 18 and the maximum is 126. The higher number indicates a worsening of schizophrenia.
Time frame: Baseline and 6 weeks
Population: Intent-to-Treat Division of Neuropharmacological Drug Products Last Observation Carried Forward (ITT-DNDP-LOCF). The ITT-DNDP-LOCF population will include all randomized patients who received at least one dose of study medication and who had at least one efficacy evaluation at Day 3 or beyond, during the double-blind treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg | Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score | -5.0 units on a scale | Standard Error 1.38 |
| 40 mg | Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score | -5.2 units on a scale | Standard Error 1.44 |
| 80 mg | Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score | -8.0 units on a scale | Standard Error 1.4 |
| 10 mg Haloperidol | Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score | -9.8 units on a scale | Standard Error 1.37 |
| Placebo | Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score | -7.9 units on a scale | Standard Error 1.38 |
p-value: <0.05ANCOVA
Secondary
Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores
The CGI Severity (CGI-S) assesses the severity of illness of the patient relative to the particular population on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time frame: Baseline and 6 weeks
Population: Intent-to-Treat Division of Neuropharmacological Drug Products Last Observation Carried Forward (ITT-DNDP-LOCF). The ITT-DNDP-LOCF population will include all randomized patients who received at least one dose of study medication and who had at least one efficacy evaluation at Day 3 or beyond, during the double-blind treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg | Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores | -0.5 units on a scale | Standard Error 0.11 |
| 40 mg | Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores | -0.4 units on a scale | Standard Error 0.12 |
| 80 mg | Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores | -0.8 units on a scale | Standard Error 0.12 |
| 10 mg Haloperidol | Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores | -0.8 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores | -0.7 units on a scale | Standard Error 0.11 |
p-value: <0.05ANCOVA
Secondary
Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores
The MADRS is a 10-item rating scale that assesses apparent and reported sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity.
Time frame: Baseline and 6 weeks
Population: Intent-to-Treat Division of Neuropharmacological Drug Products Last Observation Carried Forward (ITT-DNDP-LOCF). The ITT-DNDP-LOCF population will include all randomized patients who received at least one dose of study medication and who had at least one efficacy evaluation at Day 3 or beyond, during the double-blind treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg | Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores | -1.3 units on scale | Standard Error 0.97 |
| 40 mg | Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores | -1.1 units on scale | Standard Error 1.02 |
| 80 mg | Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores | -2.5 units on scale | Standard Error 0.98 |
| 10 mg Haloperidol | Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores | -2.7 units on scale | Standard Error 0.96 |
| Placebo | Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores | -1.9 units on scale | Standard Error 0.97 |
p-value: <0.05ANCOVA
Secondary
Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores
The PANSS Positive and Negative Syndrome Scale)is a 30-item scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. Each item is rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme). Scores range from 30-210 with higher scores representing a worsening of schizophrenia.
Time frame: Baseline and 6 weeks
Population: Intent-to-Treat Division of Neuropharmacological Drug Products Last Observation Carried Forward (ITT-DNDP-LOCF). The ITT-DNDP-LOCF population will include all randomized patients who received at least one dose of study medication and who had at least one efficacy evaluation at Day 3 or beyond, during the double-blind treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg | Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores | -7.1 units on a scale | Standard Error 2.31 |
| 40 mg | Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores | -7.2 units on a scale | Standard Error 2.42 |
| 80 mg | Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores | -13.6 units on a scale | Standard Error 2.34 |
| 10 mg Haloperidol | Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores | -16.0 units on a scale | Standard Error 2.29 |
| Placebo | Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores | -12.3 units on a scale | Standard Error 2.32 |
p-value: <0.05ANCOVA