Schizophrenia, Schizoaffective Disorder
Conditions
Brief summary
This study will investigate the efficacy and safety of RO6889450 as monotherapy in participants experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder.
Interventions
DRUGRO6889450
Participants will receive oral RO6889450 QD.
DRUGPlacebo
Participants will receive oral placebo QD.
DRUGRisperidone
Participants will receive oral risperidone QD.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be 18 to 45 years of age inclusive * Participants with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI) * Disease duration \</=10 years * Have a current acute exacerbation of schizophrenia of no more than 8 weeks before screening visit and no current signs of apparent lack of treatment response * At the time of screening, the participant needs to be either hospitalized or requiring inpatient psychiatric care according to clinical judgment. If the participant has been hospitalized for the current exacerbation, the hospitalization has to be of a maximum of 1 week prior to screening. * In previous exacerbations and hospitalizations, the subject has shown a pattern of response to appropriate antipsychotic treatment * Medically stable over a period of 3 months (non-psychiatric conditions) prior to screening visit and not expected to require hospitalization or change of treatment for non-psychiatric conditions for the duration of the study * Screening and baseline CGI-S \>/=4 (moderate or worse) * Screening and baseline PANSS total score \>= 80 * Based on screening and baseline PANSS, scores of \>/= 4 (moderate or worse) on 2 or more of the following items: delusions, conceptual disorganization, unusual thought content, hallucinatory behavior, or suspiciousness/persecution * Body mass index between 18 and 35 kg/m2 inclusive * Male and female participants; female participants agree to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 28 days after the last dose of study drug Additional inclusion criteria for optional 36-Week Safety Extension Phase * Successful completion of the 12-week treatment period * No signs or symptoms of worsening of the psychiatric or medical status that would preclude the patient from the participation in the 36-Week Safety Extension Phase or affect their ability to comply with the study requirements.
Exclusion criteria
* Has been inpatient for \> 1 week or had any other hospitalization for acute exacerbation of schizophrenia or schizoaffective disorder within the prior 8 weeks or signs of lack of response to antipsychotic treatment * Disease duration \> 10 years * Is currently an inpatient on an involuntary basis * 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) or any suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessment within one month from screening or between screening and baseline * Lifetime history of homicidal behavior * Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5 * Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder) * A prior or current general medical condition that might be impairing cognition or other psychiatric functioning (e.g., migraine headaches requiring prophylaxis treatment, head trauma, dementia, seizure disorder, stroke; or neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, or endocrine conditions) * Clinically significant abnormalities in laboratory safety test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), including a) Aspartate aminotransferase (AST), OR alanine aminotransferase (ALT) 2 x upper limit of normal (ULN), OR total bilirubin \> 1.5 ULN with the exception of known Gilbert syndrome. b) Serum creatinine \> 1.5 ULN * Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV, untreated), or human immunodeficiency virus (HIV)-1 and -2. HCV participants who have been successfully treated and who test negative for HCV RNA are eligible for entry into the study * Tardive dyskinesia that is moderate to severe or requires treatment * History of neuroleptic malignant syndrome * Average triplicate QTcF interval greater than 450 msec for males and 470 msec for females or other clinically significant abnormality on screening ECG based on centralized reading * Participant for whom risperidone is contraindicated or who have a documented history of lack of response or intolerance to risperidone or paliperidone or participants with known hypersensitivity to risperidone, paliperidone, or to any excipients in Risperdal * Participant treated with a long acting injectable antipsychotic or other antipsychotics that cannot be washed-out within the allotted screening period * History of electro-convulsive therapy (ECT) for any reason * Participant treated with clozapine at any dose within 12 months of screening visit or participants treated with clozapine at 200 mg/day or above at any time; low dose (\< 200mg/day) use for insomnia or dyskinesia longer than 12 months prior to screening visit is permitted * Participants currently receiving a psychotropic or other medication used as a psychotropic, which cannot be discontinued during the screening period * Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cocaine and barbiturates. In case of positive urine drug screen for cannabinoids, the participant may be allowed to enter the study if approved by Medical Monitor * Participant has previously received RO6889450 * Participant received an investigational drug within 28 days or five times the half-life of the investigational drug prior to the first study drug administration * Diagnosis of COVID-19 infection (confirmed or presumptive) 4 weeks prior to screening or during screening. Participants can be re-screened after 4 weeks of full recovery in addition to investigator and/or institutional approval to enroll
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Week 4 (Day 28) | The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | Baseline to Week 12 | The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity. |
| Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Week 4 (Day 28) | The CGI-S measures global severity of illness at a given point in time using a 7-point scale, where 1 = no symptoms and 7 = very severe symptoms. |
| Clinical Global Impression - Improvement (CGI-I) Scores | Week 4 (Day 28) | The CGI-I measures change from the baseline state at subsequent visits using a 7-point scale, where 1 = very much improved and 7 = very much worse. |
| PANSS Total Score at Week 12 | Week 12 | The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity. |
| Change From Baseline in PANSS Factor Scores at Week 4 | Week 4 (Day 28) | PANSS factors are modified groupings of the 30 PANSS items from the original three subscales (positive, negative, and general psychopathology). Each item is rated on a scale of 1 (absent) to 7 (most extreme). The positive symptom factor contains 8 items (score range 8-56); the negative symptom and disorganized thought/cognition factors contain 7 items (score range 7-49); the uncontrolled hostility/excitement, expressive deficit, and anxiety/depression factors contain 4 items (score range 4-28); and the avolition domain contains 3 items (score range 3-21). The negative and positive totals each have a range of 7-49 and the general total has a range of 16-112. Higher scores indicate higher symptom severity. |
| CGI-S up to Week 12 | Up to Week 12 | The CGI-S measures global severity of illness at a given point in time using a 7-point scale, where 1 = no symptoms and 7 = very severe symptoms. |
| CGI-I up to Week 12 | Up to Week 12 | The CGI-I measures change from the baseline state at subsequent visits using a 7-point scale, where 1 = very much improved and 7 = very much worse. |
| Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment | after 4-week treatment | The RDQ is a tool used to assess inpatients with schizophrenia on their readiness for discharge from inpatient treatment. It consists of five items that assess suicidality/homicidality, control of aggression/impulsivity, activities of daily living, medication-taking, and delusions/hallucinations interfering with functioning and global status. An additional item examines the overall clinical state of the patient and the final question assesses readiness for discharge. The values reported are the proportion (expressed as a percentage) of participants in each analysis group considered ready for discharge according to the RDQ. |
| Plasma Concentration of RO6889450 | Day 7 - Day 336 | — |
| Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Weeks 4, 8, and 12 | The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity. |
Countries
Japan, Russia, Ukraine, United States
Participant flow
Pre-assignment details
287 participants initially randomized in the double-blind treatment period. 11 excluded from final analysis due to having not received assigned study medication or because of re-enrollment. Participants were not required to participate in all study parts and those that did not continue to the double-blind treatment period either discontinued the study during the double-blind treatment period or exited the study after completing the period. 197 continued to the double-blind extension period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension.
Note: This arm was only in the double-blind treatment period. | 72 |
| RO6889450 45 mg Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks. | 65 |
| RO6889450 150 mg Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks. | 68 |
| Risperidone 4 mg Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks. | 71 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Double-blind Treatment Period | Adverse Event | 6 | 4 | 5 | 1 | 0 | 0 |
| Double-blind Treatment Period | Lack of Efficacy | 3 | 3 | 5 | 1 | 0 | 0 |
| Double-blind Treatment Period | Physician Decision | 1 | 0 | 1 | 0 | 0 | 0 |
| Double-blind Treatment Period | Withdrawal by Subject | 7 | 9 | 5 | 12 | 0 | 0 |
| Extension Period | Adverse Event | 0 | 1 | 4 | 3 | 1 | 3 |
| Extension Period | Death | 0 | 0 | 0 | 0 | 0 | 1 |
| Extension Period | Lack of Efficacy | 0 | 4 | 4 | 1 | 3 | 3 |
| Extension Period | Lost to Follow-up | 0 | 1 | 5 | 2 | 3 | 2 |
| Extension Period | Non-compliance with study drug | 0 | 1 | 0 | 0 | 0 | 1 |
| Extension Period | Other | 0 | 2 | 0 | 0 | 0 | 0 |
| Extension Period | Physician Decision | 0 | 2 | 0 | 1 | 1 | 0 |
| Extension Period | Withdrawal by Subject | 0 | 3 | 7 | 11 | 8 | 4 |
Baseline characteristics
| Characteristic | Placebo | RO6889450 45 mg | RO6889450 150 mg | Risperidone 4 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.2 Years STANDARD_DEVIATION 7.1 | 34.0 Years STANDARD_DEVIATION 7 | 32.3 Years STANDARD_DEVIATION 6.5 | 32.9 Years STANDARD_DEVIATION 7.1 | 33.1 Years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 11 Participants | 8 Participants | 10 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 54 Participants | 60 Participants | 61 Participants | 239 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 27 Participants | 32 Participants | 31 Participants | 123 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 37 Participants | 35 Participants | 32 Participants | 39 Participants | 143 Participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants | 15 Participants | 18 Participants | 71 Participants |
| Sex: Female, Male Male | 53 Participants | 46 Participants | 53 Participants | 53 Participants | 205 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 65 | 0 / 68 | 0 / 71 | 0 / 25 | 1 / 25 | 0 / 41 | 0 / 45 | 0 / 53 |
| other Total, other adverse events | 23 / 72 | 14 / 65 | 23 / 68 | 36 / 71 | 5 / 25 | 6 / 25 | 7 / 41 | 12 / 45 | 5 / 53 |
| serious Total, serious adverse events | 1 / 72 | 2 / 65 | 1 / 68 | 0 / 71 | 3 / 25 | 3 / 25 | 1 / 41 | 6 / 45 | 1 / 53 |
Outcome results
Primary
Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity.
Time frame: Week 4 (Day 28)
Population: The efficacy analysis population (EAP) included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Day 28 | 88.69 Units on a scale | Standard Deviation 20.18 |
| Placebo | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Baseline | 99.38 Units on a scale | Standard Deviation 11.36 |
| RO6889450 45 mg | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Day 28 | 88.94 Units on a scale | Standard Deviation 17.03 |
| RO6889450 45 mg | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Baseline | 98.54 Units on a scale | Standard Deviation 9.51 |
| RO6889450 150 mg | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Day 28 | 85.18 Units on a scale | Standard Deviation 17.67 |
| RO6889450 150 mg | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Baseline | 100.53 Units on a scale | Standard Deviation 12.25 |
| Risperidone 4 mg | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Day 28 | 78.04 Units on a scale | Standard Deviation 15.78 |
| Risperidone 4 mg | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Baseline | 100.03 Units on a scale | Standard Deviation 10.56 |
p-value: 0.84990% CI: [-4.58, 5.78]Mixed Models Analysis
p-value: 0.36290% CI: [-7.96, 2.29]Mixed Models Analysis
p-value: 0.00190% CI: [-15.46, -5.43]Mixed Models Analysis
Secondary
CGI-I up to Week 12
The CGI-I measures change from the baseline state at subsequent visits using a 7-point scale, where 1 = very much improved and 7 = very much worse.
Time frame: Up to Week 12
Population: The efficacy analysis population (EAP) included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CGI-I up to Week 12 | Day 7 | 3.54 Units on a scale | Standard Deviation 0.66 |
| Placebo | CGI-I up to Week 12 | Week 12 | 2.33 Units on a scale | Standard Deviation 1 |
| RO6889450 45 mg | CGI-I up to Week 12 | Day 7 | 3.76 Units on a scale | Standard Deviation 0.78 |
| RO6889450 45 mg | CGI-I up to Week 12 | Week 12 | 2.73 Units on a scale | Standard Deviation 1.56 |
| RO6889450 150 mg | CGI-I up to Week 12 | Week 12 | 2.30 Units on a scale | Standard Deviation 0.91 |
| RO6889450 150 mg | CGI-I up to Week 12 | Day 7 | 3.54 Units on a scale | Standard Deviation 0.78 |
| Risperidone 4 mg | CGI-I up to Week 12 | Day 7 | 3.56 Units on a scale | Standard Deviation 0.84 |
| Risperidone 4 mg | CGI-I up to Week 12 | Week 12 | 2.65 Units on a scale | Standard Deviation 0.93 |
| Risperidone 4 mg | CGI-I up to Week 12 | Week 12 | 2.00 Units on a scale | Standard Deviation 0.82 |
| Risperidone 4 mg | CGI-I up to Week 12 | Day 7 | 3.38 Units on a scale | Standard Deviation 0.84 |
Secondary
CGI-S up to Week 12
The CGI-S measures global severity of illness at a given point in time using a 7-point scale, where 1 = no symptoms and 7 = very severe symptoms.
Time frame: Up to Week 12
Population: The efficacy analysis population (EAP) included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CGI-S up to Week 12 | Week 12 | 3.33 Units on a scale | Standard Deviation 1 |
| Placebo | CGI-S up to Week 12 | Baseline | 5.28 Units on a scale | Standard Deviation 0.54 |
| RO6889450 45 mg | CGI-S up to Week 12 | Week 12 | 3.73 Units on a scale | Standard Deviation 1.27 |
| RO6889450 45 mg | CGI-S up to Week 12 | Baseline | 5.16 Units on a scale | Standard Deviation 0.47 |
| RO6889450 150 mg | CGI-S up to Week 12 | Week 12 | 3.56 Units on a scale | Standard Deviation 1.01 |
| RO6889450 150 mg | CGI-S up to Week 12 | Baseline | 5.05 Units on a scale | Standard Deviation 0.5 |
| Risperidone 4 mg | CGI-S up to Week 12 | Baseline | 5.16 Units on a scale | Standard Deviation 0.6 |
| Risperidone 4 mg | CGI-S up to Week 12 | Week 12 | 3.90 Units on a scale | Standard Deviation 0.85 |
| Risperidone 4 mg | CGI-S up to Week 12 | Week 12 | 3.06 Units on a scale | Standard Deviation 0.81 |
| Risperidone 4 mg | CGI-S up to Week 12 | Baseline | 5.26 Units on a scale | Standard Deviation 0.62 |
Secondary
Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores
The CGI-S measures global severity of illness at a given point in time using a 7-point scale, where 1 = no symptoms and 7 = very severe symptoms.
Time frame: Week 4 (Day 28)
Population: The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Baseline | 5.13 Units on a scale | Standard Deviation 0.5 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Day 28 | 4.42 Units on a scale | Standard Deviation 1.07 |
| RO6889450 45 mg | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Day 28 | 4.35 Units on a scale | Standard Deviation 0.99 |
| RO6889450 45 mg | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Baseline | 5.09 Units on a scale | Standard Deviation 0.52 |
| RO6889450 150 mg | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Baseline | 5.25 Units on a scale | Standard Deviation 0.63 |
| RO6889450 150 mg | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Day 28 | 4.29 Units on a scale | Standard Deviation 0.85 |
| Risperidone 4 mg | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Baseline | 5.27 Units on a scale | Standard Deviation 0.61 |
| Risperidone 4 mg | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores | Day 28 | 3.88 Units on a scale | Standard Deviation 0.94 |
Secondary
Change From Baseline in PANSS Factor Scores at Week 4
PANSS factors are modified groupings of the 30 PANSS items from the original three subscales (positive, negative, and general psychopathology). Each item is rated on a scale of 1 (absent) to 7 (most extreme). The positive symptom factor contains 8 items (score range 8-56); the negative symptom and disorganized thought/cognition factors contain 7 items (score range 7-49); the uncontrolled hostility/excitement, expressive deficit, and anxiety/depression factors contain 4 items (score range 4-28); and the avolition domain contains 3 items (score range 3-21). The negative and positive totals each have a range of 7-49 and the general total has a range of 16-112. Higher scores indicate higher symptom severity.
Time frame: Week 4 (Day 28)
Population: The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Day 28 | 10.81 Units on a scale | Standard Deviation 4.01 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Baseline | 23.58 Units on a scale | Standard Deviation 5.44 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Day 28 | 42.43 Units on a scale | Standard Deviation 10.68 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Baseline | 10.94 Units on a scale | Standard Deviation 3.94 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Baseline | 10.89 Units on a scale | Standard Deviation 3.97 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Day 28 | 27.72 Units on a scale | Standard Deviation 7.03 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Day 28 | 23.61 Units on a scale | Standard Deviation 6.64 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Baseline | 26.86 Units on a scale | Standard Deviation 3.6 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Day 28 | 19.69 Units on a scale | Standard Deviation 6.25 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Day 28 | 10.09 Units on a scale | Standard Deviation 4.83 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Baseline | 11.58 Units on a scale | Standard Deviation 3.39 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Day 28 | 21.63 Units on a scale | Standard Deviation 6.04 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Day 28 | 9.56 Units on a scale | Standard Deviation 4.03 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Baseline | 31.40 Units on a scale | Standard Deviation 3.59 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Baseline | 15.99 Units on a scale | Standard Deviation 3.16 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Baseline | 48.42 Units on a scale | Standard Deviation 6.24 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Baseline | 24.10 Units on a scale | Standard Deviation 5.29 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Day 28 | 14.04 Units on a scale | Standard Deviation 3.7 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Baseline | 21.86 Units on a scale | Standard Deviation 4.43 |
| Placebo | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Day 28 | 22.65 Units on a scale | Standard Deviation 5.81 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Baseline | 21.43 Units on a scale | Standard Deviation 4.66 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Day 28 | 20.63 Units on a scale | Standard Deviation 4.94 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Baseline | 23.65 Units on a scale | Standard Deviation 4.5 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Day 28 | 21.27 Units on a scale | Standard Deviation 6.63 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Day 28 | 10.69 Units on a scale | Standard Deviation 4.39 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Baseline | 48.69 Units on a scale | Standard Deviation 5.49 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Baseline | 23.02 Units on a scale | Standard Deviation 5.19 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Baseline | 12.91 Units on a scale | Standard Deviation 2.92 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Day 28 | 43.71 Units on a scale | Standard Deviation 9.06 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Day 28 | 13.67 Units on a scale | Standard Deviation 4.42 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Day 28 | 21.82 Units on a scale | Standard Deviation 5.85 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Day 28 | 9.10 Units on a scale | Standard Deviation 4.33 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Day 28 | 28.06 Units on a scale | Standard Deviation 6.14 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Baseline | 30.66 Units on a scale | Standard Deviation 3.84 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Baseline | 26.20 Units on a scale | Standard Deviation 4.19 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Day 28 | 23.41 Units on a scale | Standard Deviation 6.14 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Day 28 | 9.88 Units on a scale | Standard Deviation 4.15 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Baseline | 15.86 Units on a scale | Standard Deviation 2.83 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Baseline | 10.31 Units on a scale | Standard Deviation 3.96 |
| RO6889450 45 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Baseline | 10.52 Units on a scale | Standard Deviation 4.07 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Baseline | 48.68 Units on a scale | Standard Deviation 6.57 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Baseline | 11.54 Units on a scale | Standard Deviation 3.4 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Day 28 | 13.73 Units on a scale | Standard Deviation 3.69 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Day 28 | 19.41 Units on a scale | Standard Deviation 6.44 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Baseline | 10.90 Units on a scale | Standard Deviation 3.79 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Day 28 | 20.80 Units on a scale | Standard Deviation 5.7 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Day 28 | 22.53 Units on a scale | Standard Deviation 5.41 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Baseline | 32.03 Units on a scale | Standard Deviation 4.89 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Baseline | 27.26 Units on a scale | Standard Deviation 5.13 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Day 28 | 22.22 Units on a scale | Standard Deviation 6.5 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Day 28 | 9.06 Units on a scale | Standard Deviation 4.08 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Baseline | 16.38 Units on a scale | Standard Deviation 3.25 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Baseline | 22.50 Units on a scale | Standard Deviation 4.82 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Day 28 | 10.16 Units on a scale | Standard Deviation 4.18 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Day 28 | 40.43 Units on a scale | Standard Deviation 8.94 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Baseline | 23.81 Units on a scale | Standard Deviation 5.36 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Baseline | 24.59 Units on a scale | Standard Deviation 4.87 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Day 28 | 26.63 Units on a scale | Standard Deviation 7.16 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Baseline | 10.65 Units on a scale | Standard Deviation 4.12 |
| RO6889450 150 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Day 28 | 9.27 Units on a scale | Standard Deviation 4.22 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Day 28 | 17.07 Units on a scale | Standard Deviation 4.66 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Baseline | 11.51 Units on a scale | Standard Deviation 3.9 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Baseline | 23.65 Units on a scale | Standard Deviation 3.78 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Day 28 | 8.50 Units on a scale | Standard Deviation 4.09 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Baseline | 31.15 Units on a scale | Standard Deviation 3.73 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals negative - Day 28 | 21.45 Units on a scale | Standard Deviation 5.13 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Anxiety/Depression - Baseline | 12.58 Units on a scale | Standard Deviation 3.67 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Positive symptom factor score - Day 28 | 24.21 Units on a scale | Standard Deviation 5.38 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Baseline | 23.34 Units on a scale | Standard Deviation 4.55 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Baseline | 27.49 Units on a scale | Standard Deviation 3.95 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Day 28 | 37.07 Units on a scale | Standard Deviation 8.12 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Disorganized thought/Cognition - Baseline | 21.45 Units on a scale | Standard Deviation 4.87 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals positive - Day 28 | 19.52 Units on a scale | Standard Deviation 5.11 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Day 28 | 12.93 Units on a scale | Standard Deviation 3.44 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Avolition - Baseline | 16.20 Units on a scale | Standard Deviation 2.73 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Totals general - Baseline | 48.89 Units on a scale | Standard Deviation 6.29 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Day 28 | 10.71 Units on a scale | Standard Deviation 3.67 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Uncontrolled hostility/excitement - Day 28 | 7.86 Units on a scale | Standard Deviation 4.06 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Expressive deficit - Baseline | 10.23 Units on a scale | Standard Deviation 3.43 |
| Risperidone 4 mg | Change From Baseline in PANSS Factor Scores at Week 4 | Negative symptom factor score - Day 28 | 20.39 Units on a scale | Standard Deviation 5.55 |
Secondary
Clinical Global Impression - Improvement (CGI-I) Scores
The CGI-I measures change from the baseline state at subsequent visits using a 7-point scale, where 1 = very much improved and 7 = very much worse.
Time frame: Week 4 (Day 28)
Population: The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores | Day 21 | 3.47 Units on a scale | Standard Deviation 1.19 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores | Day 7 | 3.87 Units on a scale | Standard Deviation 0.86 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores | Day 14 | 3.63 Units on a scale | Standard Deviation 0.94 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores | Day 28 | 3.27 Units on a scale | Standard Deviation 1.29 |
| RO6889450 45 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 28 | 3.27 Units on a scale | Standard Deviation 1.17 |
| RO6889450 45 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 14 | 3.39 Units on a scale | Standard Deviation 0.95 |
| RO6889450 45 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 7 | 3.60 Units on a scale | Standard Deviation 0.76 |
| RO6889450 45 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 21 | 3.28 Units on a scale | Standard Deviation 1.06 |
| RO6889450 150 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 7 | 3.56 Units on a scale | Standard Deviation 0.88 |
| RO6889450 150 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 28 | 2.96 Units on a scale | Standard Deviation 0.93 |
| RO6889450 150 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 14 | 3.33 Units on a scale | Standard Deviation 0.9 |
| RO6889450 150 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 21 | 3.13 Units on a scale | Standard Deviation 1.06 |
| Risperidone 4 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 14 | 2.99 Units on a scale | Standard Deviation 1.01 |
| Risperidone 4 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 7 | 3.40 Units on a scale | Standard Deviation 0.87 |
| Risperidone 4 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 21 | 2.79 Units on a scale | Standard Deviation 1.01 |
| Risperidone 4 mg | Clinical Global Impression - Improvement (CGI-I) Scores | Day 28 | 2.43 Units on a scale | Standard Deviation 0.89 |
Secondary
PANSS Total Score at Week 12
The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity.
Time frame: Week 12
Population: The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PANSS Total Score at Week 12 | Week 12 | 75.10 Units on a scale | Standard Deviation 17.53 |
| Placebo | PANSS Total Score at Week 12 | Baseline | 103.44 Units on a scale | Standard Deviation 12.58 |
| RO6889450 45 mg | PANSS Total Score at Week 12 | Week 12 | 76.73 Units on a scale | Standard Deviation 21.09 |
| RO6889450 45 mg | PANSS Total Score at Week 12 | Baseline | 99.12 Units on a scale | Standard Deviation 10.16 |
| RO6889450 150 mg | PANSS Total Score at Week 12 | Week 12 | 76.25 Units on a scale | Standard Deviation 17.89 |
| RO6889450 150 mg | PANSS Total Score at Week 12 | Baseline | 98.66 Units on a scale | Standard Deviation 9.64 |
| Risperidone 4 mg | PANSS Total Score at Week 12 | Week 12 | 79.30 Units on a scale | Standard Deviation 13.68 |
| Risperidone 4 mg | PANSS Total Score at Week 12 | Baseline | 99.00 Units on a scale | Standard Deviation 11.37 |
| Risperidone 4 mg | PANSS Total Score at Week 12 | Week 12 | 67.74 Units on a scale | Standard Deviation 11.5 |
| Risperidone 4 mg | PANSS Total Score at Week 12 | Baseline | 100.30 Units on a scale | Standard Deviation 11.49 |
Secondary
Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment
The RDQ is a tool used to assess inpatients with schizophrenia on their readiness for discharge from inpatient treatment. It consists of five items that assess suicidality/homicidality, control of aggression/impulsivity, activities of daily living, medication-taking, and delusions/hallucinations interfering with functioning and global status. An additional item examines the overall clinical state of the patient and the final question assesses readiness for discharge. The values reported are the proportion (expressed as a percentage) of participants in each analysis group considered ready for discharge according to the RDQ.
Time frame: after 4-week treatment
Population: The efficacy analysis population (EAP) included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment | 88.9 Percentage of participants |
| RO6889450 45 mg | Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment | 83.1 Percentage of participants |
| RO6889450 150 mg | Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment | 89.7 Percentage of participants |
| Risperidone 4 mg | Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment | 97.2 Percentage of participants |
Secondary
Plasma Concentration of RO6889450
Time frame: Day 7 - Day 336
Population: The efficacy analysis population (EAP) included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of RO6889450 | Day 84 | 77.11 ng/mL | Geometric Coefficient of Variation 85.5 |
| Placebo | Plasma Concentration of RO6889450 | Day 42 | 59.99 ng/mL | Geometric Coefficient of Variation 248.3 |
| Placebo | Plasma Concentration of RO6889450 | Day 28 | 49.67 ng/mL | Geometric Coefficient of Variation 155.4 |
| Placebo | Plasma Concentration of RO6889450 | Day 56 | 70.99 ng/mL | Geometric Coefficient of Variation 320.4 |
| RO6889450 45 mg | Plasma Concentration of RO6889450 | Day 42 | 274.58 ng/mL | Geometric Coefficient of Variation 208.8 |
| RO6889450 45 mg | Plasma Concentration of RO6889450 | Day 84 | 165.99 ng/mL | Geometric Coefficient of Variation 963 |
| RO6889450 45 mg | Plasma Concentration of RO6889450 | Day 56 | 217.65 ng/mL | Geometric Coefficient of Variation 491.6 |
| RO6889450 45 mg | Plasma Concentration of RO6889450 | Day 28 | 212.27 ng/mL | Geometric Coefficient of Variation 25 |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 7 | 99.50 ng/mL | Geometric Coefficient of Variation 69.2 |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 14 | 91.53 ng/mL | Geometric Coefficient of Variation 111.4 |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 84 | 92.24 ng/mL | Geometric Coefficient of Variation 128.5 |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 168 | 95.39 ng/mL | Geometric Coefficient of Variation 46 |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 336 | 4.13 ng/mL | — |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 28 | 94.57 ng/mL | Geometric Coefficient of Variation 108.1 |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 42 | 108.57 ng/mL | Geometric Coefficient of Variation 76.4 |
| RO6889450 150 mg | Plasma Concentration of RO6889450 | Day 56 | 108.59 ng/mL | Geometric Coefficient of Variation 55.5 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 336 | 139.71 ng/mL | Geometric Coefficient of Variation 120.6 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 168 | 733.98 ng/mL | Geometric Coefficient of Variation 65.5 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 56 | 237.42 ng/mL | Geometric Coefficient of Variation 541.2 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 42 | 390.65 ng/mL | Geometric Coefficient of Variation 138.4 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 84 | 265.09 ng/mL | Geometric Coefficient of Variation 353.6 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 14 | 463.21 ng/mL | Geometric Coefficient of Variation 73.6 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 7 | 423.83 ng/mL | Geometric Coefficient of Variation 43.2 |
| Risperidone 4 mg | Plasma Concentration of RO6889450 | Day 28 | 419.41 ng/mL | Geometric Coefficient of Variation 93 |
Secondary
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity.
Time frame: Baseline to Week 12
Population: The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 2 | 2.8 Proportion expressed as percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 1 | 18.1 Proportion expressed as percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 3 | 31.9 Proportion expressed as percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 1 | 0 Proportion expressed as percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 4 | 8.3 Proportion expressed as percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 4 | 30.6 Proportion expressed as percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 2 | 26.4 Proportion expressed as percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 3 | 2.8 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 4 | 7.7 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 1 | 1.5 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 3 | 7.7 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 2 | 3.1 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 2 | 24.6 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 3 | 32.3 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 4 | 32.3 Proportion expressed as percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 1 | 26.2 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 1 | 1.5 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 3 | 2.9 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 4 | 8.8 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 2 | 36.8 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 3 | 38.2 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 4 | 36.8 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 1 | 27.9 Proportion expressed as percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 2 | 4.4 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 4 | 14.1 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 3 | 59.2 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 1 | 25.4 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 2 | 43.7 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 20% improvement - Week 4 | 59.2 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 1 | 2.8 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 2 | 4.2 Proportion expressed as percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score | 50% improvement - Week 3 | 14.1 Proportion expressed as percentage |
Secondary
Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12
The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity.
Time frame: Weeks 4, 8, and 12
Population: The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 8 | 36.0 Proportion expressed as a percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 12 | 28.0 Proportion expressed as a percentage |
| Placebo | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 4 | 40.0 Proportion expressed as a percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 4 | 36.0 Proportion expressed as a percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 8 | 28.0 Proportion expressed as a percentage |
| RO6889450 45 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 12 | 28.0 Proportion expressed as a percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 12 | 48.8 Proportion expressed as a percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 8 | 43.9 Proportion expressed as a percentage |
| RO6889450 150 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 4 | 46.3 Proportion expressed as a percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 12 | 28.9 Proportion expressed as a percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 8 | 37.8 Proportion expressed as a percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 4 | 53.3 Proportion expressed as a percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 8 | 69.8 Proportion expressed as a percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 4 | 75.5 Proportion expressed as a percentage |
| Risperidone 4 mg | Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12 | Week 12 | 50.9 Proportion expressed as a percentage |