Schizophrenia
Conditions
Keywords
Lurasidone, Latuda, Schizophrenia
Brief summary
This is a 12-week, multi-center, open-label extension study designed to evaluate the longer-term safety, tolerability and effectiveness of lurasidone for the treatment of subjects with schizophrenia.
Detailed description
This is a 12-week, multi-center, open-label extension study designed to evaluate the longer-term safety, tolerability and effectiveness of lurasidone for the treatment of subjects with schizophrenia who have participated in Study D1050238, a double-blind, placebo-controlled, randomized withdrawal study of lurasidone for the maintenance treatment of subjects with schizophrenia. Subjects who have completed the 28-week double-blind phase or who have experienced a protocol-defined relapse event during the double-blind phase of study D1050238 will have the option to participate in this study. In addition, if/when the study is discontinued by the sponsor, all subjects participating in the open-label phase and the double-blind phase of study D1050238 will have the option to participate in this extension study
Interventions
DRUGLurasidone
Lurasidone 40-80 mg taken orally taken once daily
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has agreed to participate by providing written informed consent. * Subject will be eligible to participate if one of the following criteria is met: * Subject has completed the 28-week double-blind phase of study D1050238 * Subject has experienced a protocol-defined relapse event during the double- blind phase in study D1050238 * Subject is participating in the open-label or double-blind phase of study D1050238 if/when study D1050238 is terminated by the sponsor. * Subject has completed all required assessments on the final study visit (Study Visit Number 42) in study D1050238. * Subject is judged by the Investigator to be suitable for participation in a 12-week clinical trial involving open-label lurasidone treatment and is able to comply with the protocol in the opinion of the Investigator.
Exclusion criteria
* Subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. * Subject answers yes to Suicidal Ideation item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS at the extension baseline visit (Study Visit Number 42 in study D1050238). Subjects who answer yes to this question must be referred by the Investigator for appropriate follow-up evaluation and treatment. * Subject tests positive for drugs of abuse or is suspected of current alcohol abuse at the extension baseline visit (Study Visit Number 42 in study D1050238). In the event a subject tests positive for cannabinoids, the Investigator will evaluate the subject's ability to abstain from cannabis during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious AEs (SAEs) | 12 weeks | Number of subjects with treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, and serious AEs (SAEs) |
| Efficacy - Change in Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline to week 12 LOCF endpoint | 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. |
| Efficacy - Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Score. | Baseline to week 12 LOCF endpoint | The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Adherence Rating Scale (BARS) | 12 weeks | The Brief Adherence Rating Scale (BARS) is a clinician-administered adherence assessment instrument that consists of four items including three questions and a visual analog rating scale (VAS) to assess the percentage (0 100%) of doses taken by the subject in the previous month. |
| Change From Baseline in Montgomery -Asberg Depression Rating Scale Total Score | Baseline to week 12 LOCF endpoint | 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. |
| Intent to Attend Assessment | 12 weeks | The ITA assessment will be administered by a research staff member. The response is recorded on a 10-point scale, with 0 = Not at all and 9 = Extremely. The ITA allowed the site to capture data regarding dropout risk. The following question was completed at the baseline visit: How likely is it that you will complete the study? |
| Smoking Questionnaire | 12 weeks | Smoking questionnaire - average number of cigarettes per day at week 12 (LOCF). |
| Short Form-12 Health Survey (SF-12) | Baseline to week 12 LOCF endpoint | The SF-12v2 is a self-administered, multipurpose short-form (SF) generic measure of health status. It was developed to be a shorter, yet valid, alternative to the SF-36 for use in large surveys of general and specific populations as well as in large longitudinal studies of health outcomes. The 12 items in the SF-12v2 are a subset of those in the SF-36; SF-12v2 includes one or two items from each of the eight health concepts with higher scores indicative of higher functioning and better health. The Physical Component Score is a composite of the Physical Functioning, Role Functioning, Bodily Pain and General Health scales. Physical Composite Scores (PCS) is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
| Modified Specific Levels of Functioning (SLOF) Total Score. | 12 weeks | The modified SLOF scale is designed to measure directly observable behavioral functioning and daily living skills of patients with chronic mental illness. The modified SLOF consists of 24 items, each item is rated on a 5-point scale and mapped to 0 to 4. The total score will be the sum of all 24 items and ranges from 0 to 96. A higher score indicates worse condition. |
Countries
France, Italy, Russia, Serbia, Slovakia, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lurasidone Lurasidone 40 - 80mg flexible dose
Lurasidone: Lurasidone 40-80 mg taken orally taken once daily | 191 |
| Total | 191 |
Baseline characteristics
| Characteristic | Lurasidone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 190 Participants |
| Age, Continuous | 42.7 Years STANDARD_DEVIATION 12.3 |
| Region of Enrollment France | 4 participants |
| Region of Enrollment Russia | 19 participants |
| Region of Enrollment Serbia | 22 participants |
| Region of Enrollment Slovakia | 15 participants |
| Region of Enrollment South Africa | 17 participants |
| Region of Enrollment United States | 114 participants |
| Sex: Female, Male Female | 76 Participants |
| Sex: Female, Male Male | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 191 |
| serious Total, serious adverse events | 13 / 191 |
Outcome results
Primary
Efficacy - Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Score.
The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity.
Time frame: Baseline to week 12 LOCF endpoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Efficacy - Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Score. | -0.48 units on a scale | Standard Deviation 1.051 |
Primary
Efficacy - Change in Positive and Negative Syndrome Scale (PANSS) Total Score
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.
Time frame: Baseline to week 12 LOCF endpoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Efficacy - Change in Positive and Negative Syndrome Scale (PANSS) Total Score | -8.4 units on a scale | Standard Deviation 15.06 |
Primary
Safety - Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious AEs (SAEs)
Number of subjects with treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, and serious AEs (SAEs)
Time frame: 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lurasidone | Safety - Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious AEs (SAEs) | TEASs leading to discontinuation | 7 participants |
| Lurasidone | Safety - Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious AEs (SAEs) | Subjects with TEAEs | 72 participants |
| Lurasidone | Safety - Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious AEs (SAEs) | Subjects with TESAEs | 13 participants |
Secondary
Brief Adherence Rating Scale (BARS)
The Brief Adherence Rating Scale (BARS) is a clinician-administered adherence assessment instrument that consists of four items including three questions and a visual analog rating scale (VAS) to assess the percentage (0 100%) of doses taken by the subject in the previous month.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Brief Adherence Rating Scale (BARS) | 99.0 percentage of monthly doses taken | Standard Deviation 3.08 |
Secondary
Change From Baseline in Montgomery -Asberg Depression Rating Scale Total Score
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.
Time frame: Baseline to week 12 LOCF endpoint
Population: Only 182 subjects had post-baseline MADRS assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Change From Baseline in Montgomery -Asberg Depression Rating Scale Total Score | -3.3 units on a scale | Standard Deviation 7.83 |
Secondary
Intent to Attend Assessment
The ITA assessment will be administered by a research staff member. The response is recorded on a 10-point scale, with 0 = Not at all and 9 = Extremely. The ITA allowed the site to capture data regarding dropout risk. The following question was completed at the baseline visit: How likely is it that you will complete the study?
Time frame: 12 weeks
Population: Only 1825 subjects answered the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Intent to Attend Assessment | 8.3 units on a scale | Standard Deviation 1.14 |
Secondary
Modified Specific Levels of Functioning (SLOF) Total Score.
The modified SLOF scale is designed to measure directly observable behavioral functioning and daily living skills of patients with chronic mental illness. The modified SLOF consists of 24 items, each item is rated on a 5-point scale and mapped to 0 to 4. The total score will be the sum of all 24 items and ranges from 0 to 96. A higher score indicates worse condition.
Time frame: 12 weeks
Population: Only 174 subjects had SLOF assessments at week 12 LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Modified Specific Levels of Functioning (SLOF) Total Score. | -1.8 units on a scale | Standard Deviation 9.55 |
Secondary
Short Form-12 Health Survey (SF-12)
The SF-12v2 is a self-administered, multipurpose short-form (SF) generic measure of health status. It was developed to be a shorter, yet valid, alternative to the SF-36 for use in large surveys of general and specific populations as well as in large longitudinal studies of health outcomes. The 12 items in the SF-12v2 are a subset of those in the SF-36; SF-12v2 includes one or two items from each of the eight health concepts with higher scores indicative of higher functioning and better health. The Physical Component Score is a composite of the Physical Functioning, Role Functioning, Bodily Pain and General Health scales. Physical Composite Scores (PCS) is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: Baseline to week 12 LOCF endpoint
Population: Only 182 subjects had post-baseline SF-12.v2 assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Short Form-12 Health Survey (SF-12) | -0.45 units on a scale | Standard Deviation 6.642 |
Secondary
Smoking Questionnaire
Smoking questionnaire - average number of cigarettes per day at week 12 (LOCF).
Time frame: 12 weeks
Population: Only 36 subjects who were smokers had the smoker questionnaire assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Smoking Questionnaire | 11.1 number of cigarettes smoked daily | Standard Deviation 9.95 |